Dihydrotestosterone - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

DIHYDROTESTOSTERONE A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET ...

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DIHYDROTESTOSTERONE

A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET

R EFERENCES

DIHYDROTESTOSTERONE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Dihydrotestosterone: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00366-X 1. Dihydrotestosterone-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on dihydrotestosterone. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON DIHYDROTESTOSTERONE .......................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Dihydrotestosterone ...................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 46 The National Library of Medicine: PubMed ................................................................................ 48 CHAPTER 2. NUTRITION AND DIHYDROTESTOSTERONE ................................................................ 97 Overview...................................................................................................................................... 97 Finding Nutrition Studies on Dihydrotestosterone..................................................................... 97 Federal Resources on Nutrition ................................................................................................... 99 Additional Web Resources ........................................................................................................... 99 CHAPTER 3. ALTERNATIVE MEDICINE AND DIHYDROTESTOSTERONE ........................................ 101 Overview.................................................................................................................................... 101 National Center for Complementary and Alternative Medicine................................................ 101 Additional Web Resources ......................................................................................................... 107 General References ..................................................................................................................... 108 CHAPTER 4. DISSERTATIONS ON DIHYDROTESTOSTERONE .......................................................... 109 Overview.................................................................................................................................... 109 Dissertations on Dihydrotestosterone........................................................................................ 109 Keeping Current ........................................................................................................................ 109 CHAPTER 5. PATENTS ON DIHYDROTESTOSTERONE .................................................................... 111 Overview.................................................................................................................................... 111 Patents on Dihydrotestosterone ................................................................................................. 111 Patent Applications on Dihydrotestosterone ............................................................................. 118 Keeping Current ........................................................................................................................ 118 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 123 Overview.................................................................................................................................... 123 NIH Guidelines.......................................................................................................................... 123 NIH Databases........................................................................................................................... 125 Other Commercial Databases..................................................................................................... 127 APPENDIX B. PATIENT RESOURCES ............................................................................................... 129 Overview.................................................................................................................................... 129 Patient Guideline Sources.......................................................................................................... 129 Finding Associations.................................................................................................................. 131 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 133 Overview.................................................................................................................................... 133 Preparation................................................................................................................................. 133 Finding a Local Medical Library................................................................................................ 133 Medical Libraries in the U.S. and Canada ................................................................................. 133 ONLINE GLOSSARIES................................................................................................................ 139 Online Dictionary Directories ................................................................................................... 139 DIHYDROTESTOSTERONE DICTIONARY .......................................................................... 141 INDEX .............................................................................................................................................. 199

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with dihydrotestosterone is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about dihydrotestosterone, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to dihydrotestosterone, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on dihydrotestosterone. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to dihydrotestosterone, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on dihydrotestosterone. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON DIHYDROTESTOSTERONE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on dihydrotestosterone.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and dihydrotestosterone, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “dihydrotestosterone” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

The Role of Dihydrotestosterone in Benign Prostatic Hyperplasia Source: Current Opinion in Urology. 2(1): 18-21. February 1992. Summary: The enzyme 5beta-reductase converts intraprostatic testosterone into the potent androgen dihydrotestosterone. This article discusses the role of dihydrotestosterone (DHT) in benign prostatic hyperplasia (BPH). Topics include androgen-dependent growth, the 5beta-reductase deficiency syndrome, development of a drug (finasteride) to inhibit 5beta-reductase production, and the biochemical and clinical efficacy of finasteride. The author focuses on the use of finasteride in early BPH to prevent further progression of the disease. 1 figure. 1 table. 17 references. (AA-M).

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Federally Funded Research on Dihydrotestosterone The U.S. Government supports a variety of research studies relating to dihydrotestosterone. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to dihydrotestosterone. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore dihydrotestosterone. The following is typical of the type of information found when searching the CRISP database for dihydrotestosterone: •

Project Title: 5 ALPHA REDUCTASE GENOTYPE, RACE PROSTATE CANCER RISK Principal Investigator & Institution: Reichardt, Juergen K.; Biochem and Molecular Biology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 31-MAY-2004 Summary: (Adapted from the Investigator's Abstract) Prostate cancer is currently the most common cancer among American men. Regulation of prostatic cell growth is largely controlled by androgens including especially dihydrotestosterone (DHT). This compound is synthesized from the male hormone testosterone by the enzyme 5-alpha reductase which is encoded in the prostate by the SRD5A2 gene. The etiology of prostate cancer appears to include increased steroid 5-alpha reductase activity particularly across racial/ethnic groups which are at very different risk for prostate cancer, such as highrisk African-Americans and lower risk Asians, the two extreme groups for risk. We have identified and characterized genetic variability in the SRD5A2 gene among various racial/ethnic groups in the US and between prostate cancer cases and controls. These investigations made use of a large multiethnic cohort in Los Angeles and Hawaii. We propose to build on and expand our studies of the SRD5A2 gene and prostate cancer by epidemiologic, genetic and biochemical methods. It is our overall hypothesis that genetic variation at the SRD5A2 locus plays a significant role in predisposition to and progression of prostate cancer and in explaining the racial/ethnic variation of risk. To this end, we intend to investigate the following interrelated six specific aims: 1) To identify all constitutional ("germline") DNA variations across the entire SRD5A2 gene that might contribute to predisposition to prostate cancer; 2) To determine the relationship between each variant identified in Specific Aim 1 to prostate cancer risk in for racial/ethnic populations: 4) To identify somatic mutations in the SRD5A2 gene involved in prostate cancer progression; 5) To characterize the biochemical properties of the somatic DNA genetic variants identified in Specific aims 1 and 4 in an in vitro model system; 6) To determine the contribution of somatic DNA genetic variants in the

2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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SRD5A2 gene to prostate cancer progression within and across racial/ethnic groups. Therefore, we will investigate the molecular basis of predisposition to prostate cancer and its progression in a multidisciplinary study rooted in molecular epidemiology with significant implications for presymptomatic identification of at-risk individuals, targeted chemoprevention and improved treatment of this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALLIUM COMPOUNDS IN CONTROL OF HUMAN PROSTATE CANCER Principal Investigator & Institution: Pinto, John T.; Institute for Cancer Prevention 1 Dana Rd Valhalla, Ny 105951549 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by the applicant) This exploratory grant seeks to establish a novel role for allium derivatives from garlic in control of human prosta cancer by acting as anti-androgens. Our preliminary observations reveal that when androgen-responsive human prostate cancer cells (LNCaP) are incubated with allium derivatives in vitro, two events take place: (a) the proliferation rate of the LNCaP cells is markedly reduced and (b) testosterone concentration rapidly decreases in both the media in which the cells are growing as well as in the cells themselves. Furthermore, when testosterone is added back to the media of LNCaP cells previously exposed to allium derivatives, the decrease in initial rate of cell proliferation is only partially restored. These preliminary results strongly suggest that allium-induced inhibition of cell proliferation and accelerated removal of testosterone are linked. We hypothesize that allium derivatives increase testosterone disappearance by accelerating conversion to inactive metabolites thereby diminishing the action of testosterone on the prostate. To test I validity of this hypothesis, we shall measure the conversion rate of testosterone to dihydrotestosterone (DHT), a more potent metabolite, through 5-alpha reductase, and the formation rate of a series of inactive testosterone metabolites, a determined by GC-MS methods. Concurrent with these experiments, we shall determine the mechanism of inhibition of growth of human prostat cancer cells by allium derivatives, whether by apoptosis or cytostasis. We shall determine where in the cell cycle growth inhibition occurs, whether or not apoptosis is induced, and whether changes in specific signal transduction proteins occ in later experiments, we shall examine effects of allium derivatives on regulatory proteins most likely to be relevant unc these conditions in modifying cell cycle transcription (i.e., cyclin B, cdk 2). These studies will then be extended in the second year to examine effects of allium derivatives on human prostate cancer cells (LNCaP C4-2) that exhibit androgen receptors but are non-responsive to its trophic effects. Together, the LNCaP and LNCaP C4-2 cell lines should serve as appropriate models, respectively, for early prostate cancer that is androgen-sensitive and later prostate cancer that is largely unresponsive to androgen manipulations. These studies should provide a creative approach to prevention and control of prostate cancer that is feasible and cosi effective, and should lead to an innovative advance in correlating certain dietary modifications and prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANDROGEN CONTROL OF TGF-BETA SIGNALING Principal Investigator & Institution: Danielpour, David; Associate Professor of Pharmacology; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106

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Timing: Fiscal Year 2004; Project Start 02-MAR-2004; Project End 28-FEB-2009 Summary: (provided by applicant): Transforming growth factor-betas (TGF-betas) are 25 kDa multifunctional autocrine/paracrine peptides with potent activity on growth suppression and apoptosis of epithelial cells. In the prostate, expression of TGF-beta protein and their receptors are induced upon androgen ablation, coincident with apoptotic cell death that occurs concomitantly in this tissue. Prostatic cells lose dependence on androgens and become resistant to TGF-beta responses during carcinogenesis, through mechanisms that remain to be defined. Further support for a tumor suppressor role of TGF-beta in the prostate comes from studies where we ablated TGF-beta signaling in two non-tumorigenic cell lines (NRP-152 and DP-153) by retroviral transduction of a dominant-negative TbetaRII, and showed the consequent loss of response to TGF-beta triggers malignant transformation. Loss of TGF-beta receptor expression is one of many potential mechanisms of TGF-beta resistance. Other pathways may involve activation of certain oncogenes that intercept TGF-beta signals at various levels. We have recently reported that DHT can directly block TGF-beta signaling through an association between AR and Smad3, leading to the transcriptional inactivation of Smad3 in LNCaP and NRP-154 prostatic epithelial cells. We provide evidence using EMSAs that AR's inhibitory effect is through blocking the binding of Smad3 to Smad Binding Elements (SBE) of target genes. Here we propose to investigate:1) the effects of DHT/AR on growth arrest and apoptosis induced by TGFbeta (or active Smad3), 2) expression of TGF-beta inducible genes by DHT/AR, 3) the structure/functional basis behind the binding of AR to Smad3, 4) possible function of AR co-activators as co-regulators or Smad3 through AR, and 5) differences in the interaction of AR with Smad3 in various nontumorigenic and tumorigenic cell lines. We believe these studies will most certainly impact on the therapeutic intervention of prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANDROGEN IMPLANT Principal Investigator & Institution: Sudaram, Kalyan; Population Council 1 Dag Hammarskjold Plaza New York, Ny 10017 Timing: Fiscal Year 2002 Summary: The need for effective and reversible methods of fertility control for men, such as those available to women, is widely recognized. Suppression of spermatogenesis by blocking gonadotropin secretion using an implant that delivers an LHRH analog represents one promising approach. However, the loss of gonadotropins results in diminished testosterone synthesis and release, requiring the long-term concomitant administration of an androgen. The aim of this project is to develop a convenient method of androgen supplementation via an implant. For this purpose we plan to utilize 7alpha-methyl-19-nortestosterone (MENT) a synthetic androgen that is considerably more potent than testosterone. We estimate the daily dose of MENT to be 300-500 mug/day, delivered subdermally via controlled release formulation. We plan to manufacture subdermal implants that would deliver this dose of MENT for up to one year. In addition to its greater potency relative to testosterone, MENT has an advantage over testosterone and its esters which are widely used as androgen supplements. The biological potency of testosterone is amplified 3 to 5 fold in the prostate, seminal vesicles, and sexual skin by its conversion to dihydrotestosterone (DHT). Although the physiological requirement for DHT in the adult male has not be established, it is suspected to be an important factor in the development of prostatic hyperplasia and prostate cancer. MENT does not undergo 5alpha-reduction in the prostate; therefore, its

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action is not amplified in this organ. Hence, MENT can be used at doses that can adequately maintain muscle mass, potency, and libido without overstimulating the prostate. In the studies proposed here, we will initially determine the biological and toxicological actions of MENT in animals and then conduct Phase 1 and 2 clinical trials in men. We will study the pharmacologic profile of MENT to determine whether, apart from its androgenic actions, MENT has residual estrogenic, progestogenic, or corticosteroid-like actions. In addition, we will study the distribution and disposition of MENT in rats. Provided that no adverse effects are seen in animal studies, pharmacokinetic studies to determine the metabolic clearance rate and bioavailability of MENT in men following intravenous and subdermal injection will be performed. In addition, MENT and testosterone will be compared for their anti- gonadotropic actions in men. One of our aims is to develop and manufacture MENT implants that would deliver a pre-determined dose in a sustained fashion for at least one year and conduct Phase 2 studies. Chronic toxicity studies will be done in rabbits and monkeys to determine the long- term safety of MENT so that the MENT implant method of androgen supplementation can proceed to large-scale clinical trials. Development of a MENT implant would not only be an important component of a male contraceptive, but such a contraceptive could be viewed as health promoting with respect to the development of prostatic disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANDROGEN RECEPTOR EXPRESSION IN DEVELOPING RAT FOREBRAIN Principal Investigator & Institution: Doncarlos, Lydia L.; Professor; Cell Bio & Neurobio & Anatomy; Loyola University Chicago Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: The overall goal of this research is to elucidate the mechanisms underlying the impact of testosterone on the developing mammalian nervous system. Testosterone sculpts the developing nervous system, insuring that the sexual phenotype of the brain matches that of the gonads. In rodents, testosterone exposure during the perinatal period permanently masculinizes not only the morphology, connectivity, and chemistry of the central nervous system but also behavioral and neuroendocrine functions. The prominent role of both estrogenic metabolites of testosterone and estrogen receptors in the process of forebrain masculinization is undisputed. Compelling accumulated data, however, have led us to hypothesize that androgen receptors are an integral component of the organizational effects of testosterone on the nervous system, and that spatial and temporal shifts in androgen receptor expression and regulation contribute to specific actions of androgens in modulation of brain development. An integrated molecular and anatomical approach will be used to examine the development and hormonal regulation of androgen receptor expression in seven functionally relevant regions of the rat brain. These studies will form the basis for behavioral experiments that will test whether androgen receptor activation during development modifies the development of sexually differentiated behaviors. Four specific hypotheses will be tested: I. The anatomical substrate for testosterone action via androgen receptors exists prenatally in the forebrain; II. Prenatal testosterone masculinizes androgen receptor mRNA and protein levels during later development; III. Hormonal regulation of androgen receptor expression is specific to the developmental stage; IV. Androgen exposure masculinizes behaviors via androgen receptor dependent mechanisms. Rats will be treated with specific steroid receptor ligands or antagonists, and androgen receptor mRNA and protein expression will be assessed using in situ hybridization, immunocytochemistry

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and western blots, or behaviors will be analyzed using standard measures of adult behavioral responses to hormones. These studies will determine when androgen receptor mRNA and protein expression begins, the cellular phenotype of androgen receptor protein expressing cells through development, whether pre or postnatal androgen modifies subsequent androgen receptor expression, and when adult patterns of androgen receptor regulation arise, and finally, whether alterations in androgen receptor expression and regulation affect sensitivity to subsequent hormone exposure and play a role in maturation of adult sexual behaviors. The studies proposed will provide data essential to dissecting the complex mechanisms underlying the process of sexual differentiation of the brain, and contribute to an understanding of developmental stage-specific responses to hormones. Further, these studies will shed light on the etiology of neurologic and mental disorders that are more prevalent in men vs. women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANDROGENS AND APOE4 INDUCED COGNITIVE IMPAIRMENTS Principal Investigator & Institution: Raber, Jacob; Behavioral Neuroscience; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (provided by the applicant): The three major human apolipoprotein (apo) E isoforms are encoded by distinct alleles (E2, e3, and c4). Compared with c2 and F3, F4 increases the risk of cognitive impairments and of developing Alzheimer's disease (AD). ApoE4 interacts with female gender, resulting in an even greater risk of developing AD. Understanding apoE-gender interactions is important for developing AD treatments. To assess how interactions between gender and apoE isoforms affect cognition, we study transgenic mice expressing human apoE isoforms in the brain and lacking mouse apoE (apoe-/-). As they age, female, but not male, apoE4 mice develop progressive impairments in spatial learning and memory in the water maze, compared with ageand sex-matched wild-type, apoe-/- or apoE3 mice. This could be relevant to cognitive impairments in human 4 carriers. Spatial memory is impaired in AD. Because the cognitive impairments are observed in female apoE4 mice that express apoE4 in neurons or astrocytes, they are independent of the cellular source of apoE. Adult female mice that express both apoE3 and apoB4 do not show cognitive deficits in the water maze, indicating that apoE3 antagonizes the effects of apoE4 on cognition. We hypothesize that sex steroids contribute to the gender-dependent behavioral alterations in apoE4 mice and that androgens antagonize the apoE4-induced behavioral alterations. Our preliminary data show that testosterone and dihydrotestosterone antagonize the memory retention deficits of adult apoE4 female mice in the water maze. We further hypothesize that androgen receptors (ARs) mediate protection against apoE4-induced cognitive impairments. ApoE4 male mice, which do not show cognitive deficits in the water maze, developed cognitive impairments after blockade of androgen receptors, whereas apoE3 male mice did not. The Specific Aims are: (1) To determine whether apoE4 has gender-specific effects on performance in hippocampus dependent tests and whether sex steroids contribute to these effects; (2) To determine whether ARs protect against apoE4-induced cognitive impairments; (3) To determine whether gender- and isoform-specific effects of apoE on AR function in the hippocampus contribute to cognitive impairments; and (4) To determine whether apoE3 antagonizes the effects of apoE4 on cognitive function. The proposed study will help to elucidate the roles of apoE isoforms in the brain and their interactions with sex steroids in cognition. This is important for our understanding of cognitive function in health as well as in diseases

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characterized by cognitive impairments and will likely advance the development of therapeutic intervention to prevent or even reverse cognitive impairments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTI-ANDROGENIC MECHANISM OF A NEW COMPOUND Principal Investigator & Institution: Shih, Charles C.; Androscience Corporation 11175 Flintkote Ave, Ste F San Diego, Ca 92121 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2003 Summary: (provided by applicant): Androgen blockage therapy may relieve the symptom of an advanced, localized prostate tumor; however, once the tumor evolves into a hormone-refractory stage, there is no effective treatment. A continuous activation of AR by antiandrogens (used in androgen blockage therapy) or other "nonconventional" agonists may contribute to prostate cancer progression in patients after androgen deprivation. Conceptually, pharmacological agents blocking AR function evoked by not only testicular androgens but also other agonists would have a superior capacity to decrease prostate cancer incidence at both the androgen-sensitive and insensitive stages. We recently found that a derivative of diferuloylmethane (Compound 4) inhibited dihydrotestosterone-induced androgen receptor transactivation in human prostate cancer cells. This agent also suppressed dihydrotestosterone-induced LNCaP cell growth. Furthermore, Compound 4 was effective in decreasing LNCaP cell growth and AR transactivation stimulated by hydroxyflutamide, a widely used antiandrogen. Based upon these preliminary data, we propose in this study to: (1) Further test whether Compound 4 abolishes AR function elicited by cyproterone acetate, estradiol, dehydroepiandrosterone, and androstenediol. These antiandrogen or steroid hormones have been documented to have residual AR agonist activity and may exist in significant amounts in patients after androgen blockage therapy. (2) Explore the mechanisms of action of Compound 4 to antagonize the AR. Compound 4 may disrupt the AR pathway at multiple steps. In this preliminary study, we will examine the most likely mechanisms- whether Compound 4 blocks androgen-induced biological response via a down-regulation of AR expression, or via a competitive suppression of testicular androgens' binding to the receptor. The discovery of a novel antiandrogen capable of preventing both androgen-dependent and androgen-independent prostate cancer may have a direct impact in clinical application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOLOGICALLY ACTIVE STEROID ANALOGS Principal Investigator & Institution: Hochberg, Richard B.; Professor; Obstetrics Gynecology & Reprod Scis; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-AUG-1984; Project End 31-JAN-2006 Summary: (Adapted from the Investigator's Abstract): Aim 1 is to synthesize 18F-labeled androgens for Positron Emission Tomography (PET) imaging of prostate cancer. The steroids include an active androgen as well as prohormones that are metabolically protected to maximize the biological signal. These steroids, labeled at C-7alpha with 18F, will be synthesized and tested for androgen receptor mediated concentration in the prostate of rats and rabbits. Aim 2 is to synthesize 18F and 123I labeled pyridyl and pyrimidyl N-substituted pyrazolo steroids based on the active glucorcorticoid, cortivazol. These steroids, containing N-activated leaving groups in their heterocyclic ring system, are designed specifically for isotope exchange reactions. The steroids are

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intended as PET or Single Photon Emission Tomography (SPECT) agents for imaging the glucocorticoid receptor rich region of the brain, the hippocampus. Aim 3 is to synthesize and test analogs of E2 that are potent estrogens and yet enzymatically labile which cause them to be converted rapidly into inactive metabolites. They are designed for use as local estrogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITION, ANDROGENS AND SEXUAL DIMORPHISM Principal Investigator & Institution: Imperato-Mcginley, Julianne L.; Chief, Division of Endocrinology; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): It is known that prenatal androgens are greatly responsible for phenotypic sexual dimorphism between the sexes by their influence on male sexual differentiation. Without androgens prenatally, the external genitalia will develop as female. However, evidence that prenatal and/or perinatal androgen exposure influences cognitive function is controversial, and the regional changes within the brain that may underlie such influences are not well understood. Our studies, using functional magnetic resonance imaging (fMRI), are designed to test the hypothesis that androgen exposure of the brain present in normal males during critical periods of differentiation and development leads to sexual dimorphism in brain function. We hypothesize that androgen exposure alters brain organization, and is responsible for sexual dimorphism between the sexes in areas of brain activation, resulting in sex differences in the performance of certain cognitive tasks as demonstrated by fMRI. The proposed studies will extend previous work on brain function organization in humans. They will address, for the first time, the issue of the androgen control of brain sexual dimorphism by studying control males and females as well as subjects with inherited disorders of androgen action, who have been characterized by molecular genetic analyses and biochemical studies. The two unique inherited conditions to be studies are complete androgen insensitivity and 5alpha-reductase deficiency. Our laboratory has been evaluating subjects with these inherited abnormalities for over twenty years. Thus, we are uniquely poised to do this study. The contrast of subjects with these conditions with each other, and with control males and females is particularly suited to dissecting out androgen effects on neurocognition. The fMRI activation methods and tasks employed have demonstrated significant sex differences in our pilot studies and will allow the more specific androgen-related hypotheses to be tested in these subject groups. These tasks include the Shepard Metzler Mental Rotation task (a visuo-spatial task), and a neutral and emotional word task, which demonstrate significant sexual dimorphism (see preliminary data). These unique studies will provide evidence for the androgen dependency of the sexually dimorphic organizational patterns of activity during the performance of certain cognitive tasks. Our studies are performed with the full fMRI resources and expertise of the Functional Neuroimaging Laboratory at Cornell, our molecular genetics laboratory, the expertise of the PI, and an experimental psychologist who has collaborated with us in the past. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORONARY REACTIVITY AND THROMBOXANE RECEPTOR EXPRESSION Principal Investigator & Institution: Hermsmeyer, R Kent.; Dimera, Inc. Suite 311 Portland, or 97210

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Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (Verbatim from the application): Coronary artery reactivity modulation is a rarely recognized, but important, consequence of gonadal steroid actions on blood vessels of primates, and thus this factor has profound significance for aging in menopausal women. This project addresses coronary hyperreactivity as an aspect of increased heart disease that is relatively overlooked. The major increase in risk of heart disease with age in women during menopause is strongly correlated with falling levels of estrogens (E), and more profoundly of progesterone (P), in the presence of continued non-ovarian E and testosterone (T) production. The androgen path, particularly dihydrotestosterone (DHT), appears to be important. The imbalance of E & P & T, the 3 ovarian steroids, is hypothesized to lead to loss of a protected state. Previously, we showed that return of even subphysiological levels of estrogen and progesterone restores normal coronary reactivity in ovariectomized primates. In this project, surgically menopausal monkeys will be treated for 2 weeks with E and/or P with controlled levels of DHT, or with 2 week increases or decreases in DHT during controlled E and P, to further probe the coronary roles of these 3 steroid hormones and their balance. E, P, and DHT appear to physiologically regulate coronary reactivity and thromboxane A2 (TxA2) receptors. DHT, the most potent known inducer of TxA2 receptors is formed locally in coronary arteries, more than is E from 1, when there is a deficiency of P. Without P, the balance favors conversion of T to DHT rather than to E. P also directly suppresses TxA2 receptor expression. Less than threshold P is thus hypothesized to be a triple adverse influence. Studies of E, P, and TxA2 receptor distribution in the coronary artery wall by immunocytochemistry, TxA2 receptor binding by Scatchard analysis, blood levels of E, P, and DHT, coronary diameter, blood pressure, and cellular studies of Ca2+ and protein kinase C will be made to probe these pathophysiological mechanisms of coronary hyperreactivity with multiple manipulations of E, P, and DHT. In vivo catheterization laboratory studies will be combined with gross and histopathological examination of coronary arteries to determine correlations with hyperreactivity and TxA2 receptor expression. Tests of E, P, and DHT effects on cellular factors underlying vasodilator and vasoconstrictor changes in primate coronary arteries are important for understanding how to protect against coronary artery risks during the post-menopausal aging process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENTAL REGULATION OF BRAIN AND BEHAVIOR Principal Investigator & Institution: Wade, Juli S.; Associate Professor; Psychology; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 01-JUN-1996; Project End 31-MAY-2006 Summary: (applicant's abstract): The proposed studies will elucidate genes and their products (proteins) that are important for the development of brain and behavior. They focus on sexual differentiation of the structure and function of the song control system and associated regions in the telencephalon of zebra finches. Only males sing, and the brain areas and muscles that control song are larger in males than in females. In many vertebrates, the development of these types of male-biased differences in behavior and morphology is regulated by gonadal steroids. In zebra finches, some masculinization can be induced with estrogen treatment, but recent data suggest that at least the forebrain song control regions differentiate independent of gonadal secretions. Therefore, a screen will be conducted to discover genes that are expressed in a sexually dimorphic pattern in the telencephalon during development of the brain regions and singing behavior. Then, proteins regulating cytoarchitecture and/or specific functions

12

Dihydrotestosterone

(e.g., learning) will be targeted for more detailed investigation. Using this strategy, female-specific transcripts for neurocalcin, a calcium binding protein, were discovered. Experiments will clarify its role and that of calcium regulation in neural development. Other studies target the role of the estrogen-sensitive protein, brain derived neurotrophic factor (BDNF), in development of the song control nuclei and regions directly associated with them that are involved in song perception. The receptors for BDNF, which supports neuronal migration and survival, are present in these regions in both sexes when males are learning to sing, and perhaps females are learning the qualities of a good song. These studies will clarify the role of learning and the brain regions that are active during song perception in females (detailed information is already available for males), and will then test the hypothesis that BDNF modulates the development of these telencephalic structures and song-related functions in both sexes. The last set of studies examines whether mechanisms regulating development in the forebrain may apply to the motor nucleus and vocal organ muscles, and whether sexual differentiation is regulated by gonadal steroids in the hindbrain and periphery, similar to other dimorphic model systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENTAL TOXICITY OF ENVIRONMENTAL CHEMICALS Principal Investigator & Institution: Vom Saal, Frederick S.; Professor; Biological Sciences; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 04-AUG-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The goal of the proposed research is to investigate mechanisms mediating disruption by bisphenol A (BPA) of cellular signalling systems during prostate and seminal vesicle development. BPA leaches from plastic resulting in significant fetal exposure in humans. Exposure of fetal mice to low doses of BPA results in a permanent increase in prostate gland number, overall size and androgen receptors (AR), while a permanent decrease in seminal vesicle size occurs; preliminary evidence suggests this is due to a decrease in the enzyme 5a-reductase, required for dihydrotestosterone (DHT) formation. Our first hypothesis is that the effects of low, environmentally relevant doses of BPA (and low doses of diethylstilbestrol, DES, as a positive control) in the fetal mouse prostate occur via binding to estrogen receptor alpha (ERa), induction of EGF and, subsequently, also IGF-1 gene activity (and synthesis of these growth factors), leading to a permanent increase in AR gene expression and AR protein. Our second hypothesis is that much higher doses of DES, but not BPA, will result in the opposite outcome and interfere with prostate development via competing with DHT for binding to AR. In the seminal vesicles, we predict that there will be a dose-dependent inhibition of EGF and IGF-1, resulting in a permanent dose-related down-regulation of 5a-reductase activity. To test these hypotheses our first specific aim is to conduct in vivo studies in which pregnant CD-1 mice are administered environmentally relevant doses of BPA (and also DES). Our second specific aim is to conduct in vivo studies with high doses of BPA and DES, up to the maximum tolerated dose. Our third specific aim involves removing the fetal urogenital sinus and Wolffian ducts for studies in primary culture to answer specific mechanistic questions by administering very low through sub-lethal doses of DES and BPA. We will also determine whether EGF and IGF-l mimic effects of DES and BPA, and if administering antibodies to these proteins inhibits effects. The fourth specific aim is to determine whether high doses of DES, but not BPA, compete with DHT for binding to AR, thus producing an antiandrogenic effect. In these studies the prostate and seminal vesicles will be examined on gestation day 18, postnatal day 3 and in adult offspring. We will

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initially focus on AR, ERa, ERB, 5a-reductase, EGF and IGF-1, and measure both mRNA levels by RT-PCR and protein levels by western blot analysis. Organ morphology will be determined by 3-D computer reconstruction from histological sections, coupled with in situ hybridization and immunocytochemistry for the above mRNAs and corresponding proteins, including markers for cell types, proliferation and apoptosis. 5a-reductase activity will be determined by radiometric assay. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIAGNOSTIC CENTER Principal Investigator & Institution: Lucia, M S.; Pathology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-MAR-2005 Summary: This competing renewal application (Diagnostic Center) is for a UO1 grant in response to RFA DK94-18. The investigators describe the widespread economic and medical problems associated with benign prostatic hyperplasia. The overall goal of the study is to test the effectiveness of pharmacological intervention in benign prostatic hyperplasia (BPH) with the hope that pharmacological intervention may prove to be superior to surgery for some patients. The goal of the project under consideration from the University of Colorado is to establish the requested Diagnostic Center for the fullscale trial. The Diagnostic Center will perform assays on peripheral blood with materials sent from several clinical centers; these assays will include prostate specific antigen, luteinizing hormone, testosterone, and dihydrotestosterone. Blood chemistries will be carried out initially and annually for the duration of the trial (described in Appendix F of the protocol). The Diagnostic Center will receive four fixed and two frozen, 18-gauge needle biopsies from each patient entered into the study. A series of slides made from the paraffin-embedded fixed needle biopsies and from the frozen needle biopsies will be examined. These slides will be examined for diagnostic purposes by the principal investigator and an unidentified fellow who will be appointed in the second year of support. Sets of slides will also be made available to the departments of pathology from the hospitals from which the biopsies are obtained. The pathology analyzed in the Diagnostic Center in Denver will be recorded on a standard form that is displayed in the material sent with the application. Additional sections of paraffin-embedded needle biopsies and the remaining materials from frozen needle biopsies will be stored for research in the future. Biopsies will be carried out at the beginning of the study, after one year, and at the end of the study. In addition to the above, immunohistochemical studies will be carried out to assess the expression of prostate specific antigen and the MIB-1 nuclear proliferation antigen. Apoptosis will be evaluated with the TUNEL immunohistochemical technique. Morphometric evaluations will be carried out "using a semiautomated image analysis approach such as that described by Shapiro et al (44)." The step by step methods of staining are listed. The investigators state that conditions stipulated in the pilot study that was carried out in their center made in "impossible.to have any information about the expected ranges of variation for each of the variables with respect to any measures of treatment outcome.From the published literature, however, it is expected that data on 280 patients will be sufficient to produce meaningful results." They state that a ".subset of approximately 280 cases will have detailed analyses performed." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Dihydrotestosterone

Project Title: DIHYDROTESTOSTERONE HYPOGONADAL MEN

(DHT)

GEL

FOR

ELDERLY

Principal Investigator & Institution: Spark, Richard; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIHYDROTESTOSTERONE IN ELDERLY HYPOGONADAL MEN Principal Investigator & Institution: Swerdloff, Ronald S.; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 905022052 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF AGING ON THE ANDROGEN SENSITIVITY OF SEX ACCESSORY TISSUES Principal Investigator & Institution: Brown, Terry R.; Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: Prostatic cell hyperplasia occurs in the dorsal and lateral lobes, but not the ventral lobe, of the aging Brown Norway rat. These findings suggest that androgen sensitivity of the Brown Norway rat prostate is lobe-specific and age-dependent. Therefore, we propose to investigate age-specific changes in the regulation of growth and differentiated cell structure and function in aging Brown Norway rats to elucidate the mechanisms of prostatic hyperplasia. The specific aims of this proposal are: 1) we will measure serum and tissue concentrations of testosterone (T), and its active metabolites dihydrotestosterone (DHT) and estradiol (E2) and determine whether changes in androgen or estrogen receptors, 5alpha- reductase or aromatase activities occur within each lobe; 2) we will determine whether age-associated intrinsic changes occur within each lobe to affect androgen sensitivity. We will pharmacologically alter androgen receptor binding, 5alpha-reductase activity and DHT levels or aromatase activity and E2 levels in young and old rats and determine whether cell specific structure and function is affected; 3) we will determine whether age-dependent and lobe-specific differences occur in cell death and cell proliferation following castration alone or when androgen is replaced; and 4) we will determine whether lobe-specific cellular hyperplasia is related to age-dependent changes in the magnitude or temporal pattern of testicular testosterone production. Growth within the ventral, lateral and dorsal prostate lobes will be assessed by tissue weight; cell structure by microscopic examination of call morphology and stereologic analysis of cell number within epithelial and stromal compartments; and function by Northern blots of specific mRNAs and Western blots of specific proteins for androgen receptor and 5alpha-reductase in all tissues, for prostate in, dorsal protein I and probasin in the ventral, dorsal and lateral prostate lobes, respectively. Growth factors and their receptors will be related to changes in androgen sensitivity and in cellular morphology. Immunocytochemistry and in situ RNA hybridization will be used to localize cell-specific expression of gene products. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF ANDROGENS ON HANTAVIRUS INFECTION Principal Investigator & Institution: Klein, Sabra L.; Molecular Microbiol and Immun; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 16-FEB-2002 Summary: Males are more susceptible to many parasite infections than females. The goal of this research proposal is to determine whether males are more susceptible to viruses, specifically hantaviruses, because androgens suppress immune function or because males engage in more androgen- dependent behaviors (e.g., aggression) that influence susceptibility to hantavirus. These studies are based on field observations of many species that report a high proportion of males being infected with hantavirus. The goal of this proposal will be met by examining: the role of sex steroid hormones in sex differences in immune responses to hantavirus infection; 2) how androgen metabolites influence the course of hantavirus infection; 3) when during ontogeny hormones influence adult susceptibility to infection; 4) whether aggressive males are more susceptible to hantavirus infection than less aggressive males. These studies represent a thorough examination of potential mechanisms that underlie population variation in hantavirus infection and serve to expand our knowledge of disease processes in general and, specifically, factors that affect susceptibility to hantavirus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF ETIOCHOLANEDIONE ON HEPATIC METABOLISM & INSULIN RESISTANC Principal Investigator & Institution: Christiansen, Mark P.; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FEMALE SEXUALITY: MODULATION BY ESTROGEN AND ANDROGEN Principal Investigator & Institution: Wallen, Kim; Dobbs Professor of Psychology and Behavi; Psychology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The hypothesis is investigated that female sexual interest is stimulated by the neural actions of ovarian estrogens and that androgens regulate the bioavailability of these estrogens through interactions with sex hormone binding globulin (SHBG). Three projects, using a rhesus monkey model of endocrine function and behavior, investigate the hormonal basis of female sexual initiation. Project I investigates sexual initiation in females across the menstrual cycle, comparing the occurrence of female sexual initiation in a social group context during normal cycles treated with an androgen receptor blocker (flutamide) or an estrogen receptor blocker (tamoxifen). This will clarify whether androgens or estrogens act neurally to modulate female sexual motivation. Project II tests the novel hypothesis that SHBG regulates bioavailable estrogens and androgens through these steroids' different affinities for SHBG. This project uses a monkey model of hormonal replacement therapy for reproductively prime females after surgical removal of their ovaries and tests the hypothesis that chronic estradiol (E2) ceases to effectively stimulate female sexual interest as estrogen is sequestered by SHBG. It further investigates whether an

16

Dihydrotestosterone

androgen, 5a-dihydrotestosterone (DHT), with a markedly higher affinity for SHBG than estradiol can acutely and rapidly reinstate female sexual interest by increasing free estradiol by displacing SHBG-bound estradiol. Ovariectomized females receiving chronic estradiol treatment mimicking mid-follicular estradiol levels will be observed for sexual initiation during chronic E2 treatment alone and following chronic E2 and an injection of DHT or E2. Concurrent administration of flutamide or tamoxifen with the estrogen or DHT will discriminate between behavioral changes resulting from the activation of neural androgen or estrogen receptors. The effects of these treatments on neuroendocrine function will also be investigated. Project III investigates whether common human hormonal replacement therapies of chronic estrogen, or chronic estrogen plus testosterone with or without concurrent progestin, can reinstate female sexual interest in reproductively prime ovariectomized female monkeys. The hypothesis will be tested that chronic progestin therapy reduces or eliminates the effectiveness of therapies that reinstate female sexual interest without progestin. These therapies will also be compared on their effects on neuroendocrine function. These studies will markedly increase our understanding of the role that ovarian steroids play in modulating women's sexuality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION OF CAR, A NEW ORPHAN NUCLEAR HORMONE RECEPTOR Principal Investigator & Institution: Moore, David D.; Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-FEB-1995; Project End 31-JAN-2003 Summary: The nuclear hormone receptor superfamily currently includes approximately 20 orphan members that do not have known ligands. The prediction that the ligands for these orphans would prove to be important new regulatory compounds has been supported by several recently described orphan - ligand matchups. PPARgamma, for example, has been found to be a receptor for thiazolidinediones, pharmacologically significant antidiabetic agents. We have identified a novel class of ligands for the orphan receptor CAR, which is a constitutive transactivator in the absence of ligand. Strikingly, this constitutive transactivation is shut off by two naturally occurring androstanes, androstanol and androstenol. We propose that these androstanes, or their metabolites, are CAR ligands, and that their mechanism of action is opposite to that of ligands for conventional receptors. Like other nuclear receptor ligands, however, we predict that the CAR ligands will have important biological functions. We propose four specific aims to determine the mechanism of their unexpected inhibitory actions, and to define the functional role of CAR and its ligands. The first aim is to test the specific hypothesis that the CAR AF-2 activation helix is displaced from an active position in the absence of ligand to an inactive position upon ligand binding. The second aim is to screen further androstanes or related compounds for similar inhibitory effects, and to identify true CAR ligands. Since the DNA binding specificity of CAR is very similar to that of the retinoic acid receptor (RAR), the third aim is to test the hypothesis that CAR ligands should affect retinoid signaling pathways. The fourth aim is to determine the consequences of knocking out the CAR gene. Our studies with CAR have already yielded a novel mechanism of action for a nuclear hormone receptor, and we believe that the new information on the actions of its steroid ligands should prove to be equally interesting and important. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONAL ANALYSIS OF THE SULFOTRANSFERASE, SULT2B1 Principal Investigator & Institution: Geese, William J.; Institute for Cancer Research Philadelphia, Pa 191112434 Timing: Fiscal Year 2002; Project Start 11-MAR-2002; Project End 08-NOV-2002 Summary: Sulfate conjugation (sulfonation) is an important pathway in the biotransformation of steroid hormones. These reactions are catalyzed by a superfamily of cytosolic sulfotransferase (SULT) enzymes. In humans, the SULT2B1 gene encodes two isoforms, SULT2B1a and SULT2B1b, that catalyze the sulfonation of steroid hormones including dehydroepiepiandrosterone and dihydrotestosterone. SULT2B1 is expressed in steroid hormone-responsive tissues including prostate and breast. The goal of this research proposal seeks to elucidate a novel regulatory pathway, catalyzed by SULT2B1, that abrogates steroid- hormone dependent cellular processes. The proposed studies will evaluate the proliferative and transcriptional responses of cells expressing SULT2B1 and naturally occurring polymorphic SULT2B1 alloenzymes toward androgens. In complementary work, the functional significance of an evolutionarily acquired, novel proline-rich domain in SULT2B1 will be evaluated for its contribution to protein-protein interactions. Finally, the functional significance of common genetic SULT2B1 polymorphisms will be evaluated. Together these studies have the potential to elucidate a novel regulatory pathway, catalyzed by SULT2B1, that abrogates steroid hormone-dependent cellular processes in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENDER DIFFERENCES IN STROKE Principal Investigator & Institution: Hurn, Patricia D.; Professor and Vice Chairman for Research; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: Our previous work emphasizes that tissue outcome from experimental stroke is gender-dependent and influenced by cellular and molecular actions of female and male sex steroids. We have shown that estrogen provides protection from cerebral injury in rodents of both sexes, even in the presence of complicating stroke risk factors such as hypertension and diabetes and in aging animals. The overall purpose of this project is to further examine inherent sex-linked injury mechanisms with emphasis on the role of 17-beta estradiol and on the principal active androgens, testosterone and dihydrotestosterone. Estrogen' s mechanisms of protection are clearly multifactorial and involve both brain and cerebral vessels. Aim 1 will further evaluate the role of estrogen receptor (ER) subtype alpha vs beta in mediating estradiol's neuroprotective mechanisms. Our preliminary data that estradiol treatment can only partially protect ER alpha deficient mice (alphaERKO) from ischemic injury. We will test the hypothesis that estradiol does not protect alphaERKO from middle cerebral artery occlusion (MCAO) as compared to wild type or ER beta deficient (betaERKO) mice. In aim 2, we will evaluate the importance of estrogen's known activation of the PI3-Akt kinase signaling to the steroid' s neuroprotective properties in experimental stroke. The hypothesis is that estradiol treatment reduces delayed damage after MCAO through enhancement of the PI3-Akt pathway activation that ordinarily occurs after ischemia. Aim 3 will determine the contribution of estradiol aromatized from testosterone in brain to neuroprotection from focal cerebral ischemia and examine mice genetically deficient in cytochrome P450 estrogen aromatase vs treated with local brain aromatase inhibitors. Most research aimed at understanding gender differences in experimental or clinical stroke has focused on the potential value of female sex steroids. An equally important issue

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remains understudied, i.e. if and how androgens alter incidence and outcome from cerebrovascular disease. Aim 4 will determine if testosterone and dihydrotestosterone (DHT) play an important role in outcome from MCAO in adult and middle-aged male animals. Our preliminary data suggest that potent androgens enhance damage in young males but provide protection in middle age-stroke. The importance of androgens to stroke is virtually uncharted territory. These findings will have broad application to patients with brain injury from stroke or reperfusion injury after invasive neurosurgical procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENDER-DIFFERENCES REPOLARIZATION/ARRHYTHMIAS

IN

CARDIAC

Principal Investigator & Institution: Salama, Guy; Professor; Cell Biology and Physiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 20-JUL-2002; Project End 30-JUN-2006 Summary: The long-term goal is to elucidate gender differences in the expression and spatial distribution of cardiac ionic channels and their functional consequences on the electrical and intracellular free Ca2+ (Cai) handling properties of the heart. Clinical studies have shown that women have longer corrected QT intervals (QTc), a greater propensity to drug-induced long QT syndrome (LQTS) and a higher incidence of sudden cardiac death than men. Differences in APD diminish after menopause implicating a modulation of ion channels by estrogen and/or testosterone. The effect of estrogen-replacement in post- menopausal women on arrhythmia vulnerability remains unknown. Female rabbits have longer APDs and QT intervals than males and a greater vulnerability to LQT-related arrhythmias. Differences in the expression and spatial distribution of IKr, IKs and/or ICa most likely account for differences in repolarization sequence, QT prolongation and enhanced susceptibility of females to arrhythmias. To characterize gender differences in Cai handling and dispersion of repolarization (DR), we propose to apply imaging techniques at high spatial and temporal resolution to simultaneously map voltage and intracellular Ca2+ transients from perfused rabbit hearts. Optical maps of APs and Cai transients q selective blockers for IKr, IKs and ICa will elucidate gender differences in the spatial distribution of these channels and will be correlated with measurements of Ito, IKr, IKs and ICa, by voltage clamping of ventricular myocytes isolated from various regions of the heart. These data will also be correlated with distributions of mRNA and protein using selective probes and antibodies for individual ion channel subunits. The specific aims are: 1) To characterize gender differences in the spatial distribution of Ito, IKr, IKs, and ICa and their functional effects on APD, repolarization and Cai handling that can be attributed to gonadal hormones. Hearts from female (q ovariectomy (OVX)), and male (q orchiectomy (ORX)) rabbits will be optically mapped (approximately 1 month later) to obtain baseline values for electrical and Cai handling. Hearts will then be treated with an IKr, IKs, and/or ICa blockers to measure changes in APD, repolarization patterns, and susceptibility to arrhythmias. Optical maps will be correlated with the distribution of ionic currents, channel mRNA levels and channel protein distribution using voltage clamp, Northern and Western blot techniques. 2) To investigate the effects of hormone replacement on the dispersion of repolarization and arrhythmia susceptibility by treating OVX and ORX rabbits with 17-beta estradiol (EST), 5alpha-dihydroxy-testosterone (DHT) for 2-3 weeks. Hearts will be examined for altered electrical and Cai handling properties, which will be correlated with changes in the distribution of ion channel currents, mRNA and protein

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levels. 3) To study gender differences in response to ischemic injury by determining the effects of acute and chronic ischemia (rabbit infarct model) on dispersion of repolarization and arrhythmias on males (q ORX) compared to females (q OVX). 4) To determine possible protective effects of estrogen replacement on ischemic injury. Changes in APD, dispersion of repolarization and arrhythmia susceptibility will be measured in an acute and chronic infarct model using rabbit hearts from OVX females with or without estrogen replacement. Such an investigation will analyze the functional effects of cardiac repolarization, a parameter that has been implicated in an underlying mechanism for the initiation and maintenance of arrhythmias and thus, will address a fundamental problem in women's health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE EXPRESSION IN PROSTATE CANCER Principal Investigator & Institution: Russell, David W.; Mcdermott Distinguished Professor; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002 Summary: (Adapted from the application) The overall objective of this application is to gain insight into gene expression in prostate disease. Research in the last project period revealed an oxidative 3alpha-hydroxysteroid dehydrogenase that converts 5alphaandrostanediol into the active prostatic, androgen dihydrotestosterone. Additionally, a nuclear transcription factor termed EPAS1, that is selectively expressed in endothelial cells and that activates endothelial cell-specific genes was isolated. We now propose to characterize the roles of these genes in the prostate and to isolate additional cDNAs encoding androgen metabolizing enzymes. In Specific Aim 1, cDNAs encoding androgen metabolizing enzymes will be isolated from prostate libraries by expression cloning in mammalian cells. The isolated cDNAs will be characterized with respect to DNA sequence, chromosomal location, tissue and cell type distribution, developmental expression patterns in the urogenital tract, and the biochemical parameters of the encoded enzyme. In Aim 2, the expression of these cDNAs, the oxidative 3alphahydroxysteroid dehydrogenase, and EPAS1, will be determined in prostate disease. Biochemical, immunochemical and molecular assays will be used to measure target protein and mRNA levels in BPH and prostatic cancer specimens provided by the Tissue Core Facility of this O?Brien Center. In Aim 3, the consequences of EPAS1 gene disruption in mice will be determined. As detailed in Preliminary Results, targeted gene disruption produced mice heterozygous for a null mutation at the Epas1 locus. Animals that are homozygous for the mutation will be characterized with respect to formation of the vasculature and angiogenesis. The Epas1 mutation will be crossed into nude mice and its effects on the propagation of prostatic tumor xenografts will be determined. Androgen metabolism and angiogenesis are crucial for the development and growth of the normal and pathologic prostate and we believe that the proposed studies will provide novel insight into these processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC AGGRESSIVENESS

EPIDEMIOLOGY

OF

PROSTATE

CANCER

Principal Investigator & Institution: Witte, John S.; Professor; Epidemiology and Biostatistics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005

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Summary: (Adapted from applicant's abstract): The aggressiveness of prostate cancer varies widely; some tumors progress to invasive, potentially life-threatening disease whereas others stay latent for an individual's remaining lifetime. Furthermore, tumor aggressiveness appears to differ between ethnic groups, with African-Americans exhibiting the highest morbidity and mortality rates of prostate cancer in the world. One promising explanation for this phenomenon is that genes influencing androgen metabolism--which drives the prostate's growth and differentiation--increase the risk of progressing to aggressive disease. Another possibility is that genes within chromosomal regions that have been identified from linkage analyses increase this risk. We propose investigating both of these possibilities with a case-control study of the relation between candidate genes/regions and the aggressiveness of prostate tumors, as outlined in the following specific aims. Specific Aim 1. We will investigate the impact on prostate tumor aggressiveness of four candidate genes involved with the androgen pathway. In this aim we will follow up on our promising data on a variant in CYP3A4, and evaluate polymorphisms in three other candidate genes that many affect dihydrotestosterone levels in the prostate. In particular, associations between aggressive prostate cancer and 1) the CYP3A4 variant;, and 2) polymorphisms in three other candidate genes potentially impacting dihydrotestosterone levels in the prostate (i.e., 5 alpha-reductase II, androgen receptor, and CYP17) will be investigated. Specific Aim 2. We will localize potential prostate tumor aggressiveness genes within candidate regions on chromosomes 5, 7, 10 and 19. Our recent work indicates that there exist relatively strong linkages between prostate tumor aggressiveness (as measured by Gleason score) and these genomic regions. This suggests that these candidate regions may contain genes that affect the progression to aggressive disease. We will undertake this aim with the complementary approaches of allelic association and loss of heterozygosity mapping. To fulfill our aims we will recruit 500 incident cases with aggressive prostate tumors, and 500 age and ethnicity matched controls from the major medical institutions in Cleveland, Ohio. We will extract DNA from case and control biospecimens, and analyze the candidate genes or markers in the chromosomal regions of interest. Then we will evaluate the relation between these genetic factors and aggressive prostate cancer--and potential effect modification by ethnicity. Detecting molecular markers for tumor aggressiveness may supply important insights into the underlying mechanism of disease, provide a valuable screening tool for non-diseased men, and help guide treatment for men diagnosed with prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GNRH GONADOTROPIN TRANSCRIPTION AND STEROID FEEDBACK Principal Investigator & Institution: Shupnik, Margaret A.; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 23-APR-2003; Project End 31-MAR-2008 Summary: GnRH pulses and sex steroids act on the pituitary to regulate the synthesis and secretion of LH and FSH. In the past funding period, we cloned the rat alphasubunit promoter, identified GnRH-responsive DNA elements and transcription factors for rat LHbeta and alpha-subunit promoters, and characterized intracellular signaling pathways mediating GnRH responses. The LHbeta promoter requires pulsatile GnRH stimulation in vivo, and has two cooperating complex DNA elements, a distal element with overlapping Sp1 and CArG box sites, and a proximal element with two bipartite sites for SF-1 and Egr-1. Both elements bind Sp1 family zinc finger proteins that could differentially affect transcription. Relative roles of these transcription factors in GnRH

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stimulation will be assessed by DNA-protein binding, chromatin immunoprecipitation (CHIP) and real-time RT-PCR, and transfection ot deletion/mutation luciferase constructs in LbetaT2 ceils. Preliminary data show that steroids both enhance (17betaestradiol (E) or pM dihydrotestosterone, DHT) and suppress (nM DHT) the GnRH transcriptional response, without steroid receptor binding to DNA. Coactivator/integrator proteins SNURF and CBP will be tested in cotransfection and protein-protein binding studies for modulation of the GnRH response. Parallel biochemical and functional strategies will be used to investigate both stimulatory and suppressive effects of steroids in normal gonadotropes and LbetaT2 cells. These include tests of altered promoter occupancy by Sp1/Egr- 1 family members in ChIP assays, rescue of suppression by overexpression of transcription factors, and alteration of gene expression by focused microarray analysis and real-time RT-PCR. Promoter regions and transcription factors mediating steroid responses will be defined. Nuclear receptor requirements will be tested with steroid antagonists, and the Tfm androgen receptor mutant mouse. Non-genomic steroid effects on intracellular signaling pathways will be measured in the absence or presence of GnRH. These studies will further our understanding of GnRH regulation of the gonadotropins, and steroid modulation of this response. This research has important implications for understanding fertility disorders such as PCOS, in which elevated circulating androgens are accompanied by altered GnRH and LH secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONAL AGENTS, ERYTHROPOIESIS, AND THE NEONATES Principal Investigator & Institution: Carmichael, Robert; Morgan State University Baltimore, Md 21251 Timing: Fiscal Year 2002 Summary: Erythropoietin (Ep), is a glycoprotein hormone produced by the kidney and has been unequivocally proven to be the prime regulator of erythropoiesis in the adult mammalian species. Experiments have been designed to test in greater detail, the hypothesis that Ep produced by anemic lactating rats is transmitted to the newborn via the maternal milk and subsequently transported from the intestine to the circulation thereby stimulating erythropoiesis in these animals. Hyper transfused and normal neonatal rats will be used in these experiments. Milk and blood plasma from anemic lactating rats will be assayed for erythropoiesis stimulating activity. Detailed morphological studies of splenic and bone marrow erythroid cells in the neonate, as well as peripheral blood, will be made to assess the response of these cells to Ep. The effects of anti-Ep and neuraminidase, substance which inactivate Ep and decrease erythropoiesis in the adult rodent will be examined to test the hypothesis that in newborn rats regulation of red cell production differs, in some respects, from that observed in the adult. In addition to the studies with Ep, other experiments are planned with some hormones of the adenohypophyseal-target endocrine organ axis. These will include adenohypophyseal growth hormone (GH), adrenocorticotrophin (ACTH), triodothyronine (T3), testosterone, 5alpha-dihydrotestosterone and estradiol. Both parenteral and oral routes of administration will be included and both peripheral blood and blood-forming organs erythropoietic parameters (described above for Ep) will be utilized to determine the effectiveness of these hormones. These experiments will provide needed information on neonatal erythropoiesis. They will be followed by studies which cyclic nucleotides in which experiments are designed to examine the effects of cyclic adenosine - 3'5' - monophosphate on erythropoiesis in neonatal rats. Minority undergraduate students will participate in all phases of this project. They will

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receive a high degree of training in biomedical research (hematological techniques), executing experiments, analysis and interpretation of scientific data, and in writing and presenting scientific papers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONAL CONTROL OF HUMAN TESTICULAR FUNCTION Principal Investigator & Institution: Bremner, William J.; Chief; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002 Summary: The general objective of this work is to define carefully the endocrine milieu that is required to maintain normal testicular function in men. In particular, we are concerned with the gonadotropin and steroid environment necessary to stimulate human spermatogenesis and steroidogenesis. We will be experimentally manipulating the hormonal environment of the testis in normal men and determining the resultant effects on spermatogenesis and steroid production. More specifically, the objectives of this work are to anser questions in four areas: 1. What are the physiological roles of follicle-stimulating hormone (FSH) in men? Is FSH required to maintain spermatogenesis in man? 2. What are the physiological roles of luteinizing hormone (LH) in men? Is LH required to maintain human pituitary stimulatory effect on testicular steroid secretion? 3. Is the conversion of testosterone (T) to dihydrotestosterone (DHT) i.e. 5alpha reduction, important in the stimulation of human spermatogenesis? What are the concentrations of T and DHT in the human testis in various experimental paradigms, and doses this information advance our understanding of the control of spermatogenesis. 4. Can the new gene array technology be applied successfully to studies of the human testis; if so, will this new technology yield additional insights into the genes controlling human spermatogenesis and steroidogenesis? This work will make use of new compounds, including recombinant human FSH and LH, a gonadotropin releasing hormone (GnRH) antagonist and a 5alpha reductase inhibitor, for exploring the normal physiologic control systems of human testicular function. Our studies are directly relevant to the development of safe, effective, reversible methods of male contraception and to the treatment of men disorders of spermatogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONAL CONTROL OF SBMA PATHOGENESIS Principal Investigator & Institution: Merry, Diane E.; Assistant Professor; Biochem & Molecular Pharmacol; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-APR-2008 Summary: (provided by applicant): Spinal and bulbar muscular atrophy (SBMA) is an adult-onset neurodegenerative disease affecting motor neurons of the anterior horn and brainstem and caused by the expansion of a polyglutamine tract within the androgen receptor (AR). Recent findings have shown that the disease is initiated by the binding of the AR to its ligand, testosterone or dihydrotestosterone, and its subsequent translocation to the nucleus. This result suggests that the manipulation of the AR ligand, and/or it's binding to the AR, is an important target for therapeutic intervention. Testosterone is metabolized to a more potent form, dihydrotestosterone (DHT), by the enzyme 5-alpha reductase. The neuronal cell type differences in the expression of this enzyme suggest that 5-alpha reductase expression in the motor neurons of the anterior

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hom and brainstem may contribute to the cell type specificity of SBMA. We propose to test the hypothesis that 5-alpha reductase expression contributes to disease pathogenesis and cell type specificity by modulating its function, using genetic and pharmacologic approaches. Lastly, recent studies indicate that the function of the AR in its normal capacity as a transcription factor is unnecessary for disease pathogenesis, suggesting that nuclear translocation alone is responsible for the onset of disease. We propose to test this hypothesis through the genetic manipulation of AR nuclear translocation in both cell and mouse models of SBMA. Since polyglutamine expansion has been shown to alter the catabolism of the mutant AR, the effect of subcellular localization on AR catabolism of the AR, as well as on its phosphorylation state will be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONAL REGULATION OF ETHANOL METABOLISM Principal Investigator & Institution: Mezey, Esteban; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUN-1977; Project End 31-MAY-2005 Summary: The objectives of the proposed studies are two-fold: 1) To investigate the mechanisms of the effects of hormones on the regulation of rat class I alcohol dehydrogenase. These studies include characterization of trans-acting factors that regulate expression of the gene, and determination of the mechanisms whereby hormones affect transcription of the gene. 2) To study mechanisms whereby acetaldehyde, the product of ethanol oxidation by alcohol dehydrogenase, stimulates fibrogenesis. These studies are focused on identifying trans-acting factors that regulate expression of the type I collagen genes, and determining whether the effect of acetaldehyde is mediated by modification of the amounts or binding affinity of these trans-acting factors to the collagen genes. Growth hormone (GH) increases alcohol dehydrogenase by increasing its synthesis at the level of transcription, while dihydrotestosterone decreases alcohol dehydrogenase by increasing its rate of degradation. It will now be determined whether the effect of GH in enhancing transcription (STAT) proteins. The pathway for degradation of alcohol dehydrogenase will be defined by determining if specific inhibitors of various pathways prevent the effect of dihydrotestosterone in increasing degradation of the enzyme. Mechanisms for the effects of acetaldehyde in enhancing collagen formation will be studied in cultured hepatic stellate cells. The role of retinoic acid (RA), retinoic acid receptors and their binding to RA-responsive elements (RARE) in the (1(I) collagen promoters will be assessed as mediators for the acetaldehyde. The role of C/EBP-beta for basal activity and for the activation of the alpha1 (I) collagen promoter by acetaldehyde will be determined in transfection experiments with the wild type and promoter mutated at the C/EBP-beta binding site and with co-transfection with a C/EBP-beta expression vector. The mechanism whereby acetaldehyde increases nuclear C/EBP-beta protein and binding to the collagen promoter will be determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONE NEUROTRANSMITTER INTERACTIONS IN THE BRAIN Principal Investigator & Institution: Hull, Elaine M.; Professor; Psychology; State University of New York at Buffalo Suite 211 Ub Commons Buffalo, Ny 14228 Timing: Fiscal Year 2002; Project Start 01-AUG-1988; Project End 30-APR-2006

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Summary: Dopamine (DA) is released in the medial preoptic area (MPOA) of male rats in the presence of a receptive female, and it facilitates their copulation. Precopulatory DA release is highly predictive of copulatory ability. Testosterone (T) increases basal and female-stimulated DA release by up-regulating nitric oxide synthase (NOS), which produces nitric oxide (NO), which in turn increases DA release. We will now determine the hormonal and cellular factors that regulate DA release in the MPOA and will also determine the consequences of MPOA DA release on amino acid neurotransmitters. Aim 1 will determine whether T metabolites applied directly to the MPOA can maintain copulation, DA release, NOS immunoreactivity and DA receptors. We will also test whether androgen receptor-containing neurons in the MPOA are also immunoreactive for subtypes of DA receptors and whether castration affects those receptors. Aim 2 will determine the cellular factors that regulate the release of dopamine in the MPOA and the immediate consequences of DA release. Interactions with cGMP, glutamate, and GABA will be studied with both microdialysis and immunocytochemistry. Aim 3 will test mechanism(s) by which sexual experience may facilitate copulation. We will test whether basal or female-stimulated MPOA DA levels are higher in experienced than in naive males and whether injection of an NMDA antagonist into the MPOA prevents the facilitative effects of repeated exposures to a female. Aim 4 will determine the nature and functional significance of a major input to the MPOA. Lesions of the medial amygdala (MeA) blocked the MPOA DA response to a female and impaired copulation. Microinjection of a DA agonist into the MPOA restored copulatory ability in males with MeA lesions. We will now test whether electrical stimulation of the MeA increases DA, glutamate, and/or GABA release in the MPOA and whether axons from the MeA end near MPOA neurons that are immunoreactive for glutamate or GABA receptors or NOS. Two major clinical treatments for erectile disorder either prolong NO's peripheral and central effects or stimulate DA receptors; however, both have undesirable side effects. This research may lead to better treatments for sexual dysfunctions with fewer side effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE RECEPTOR ACTIONS ON MIDBRAIN DOPAMINE PATHWAYS Principal Investigator & Institution: Creutz, Lela M.; Neurobiology and Behavior; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2006 Summary: (provided by applicant): This proposal will evaluate roles of intracellular estrogen and androgen receptors in the differential hormone modulation of identified midbrain dopamine (DA) systems. Sex differences in the epidemiology of schizophrenia and Parkinson's disease, disorders with underlying DA pathology, as well as studies of hormone manipulations in rats and other mammals suggest that the mesostriatal and mesolimbic DA systems respond differently to androgen and estrogen stimulation. Although some effects may occur independently of intracellular receptors, these studies build on existing data indicating that midbrain DA systems are also subject to intracellular estrogen and androgen receptor-mediated actions. This proposal posits that these influences are anatomically segregated and differentially poised to influence DA neurons in mesostriatal verses mesolimhic pathways. To test this hypothesis, experiments will combine methods of tract-tracing, and single- double- and triple-label immunocytochemistry to localize hormone receptors to specific pathways, and will then use hormone manipulations to test the response of these pathways to receptor-mediated estrogen and androgen stimulation. These studies will concretely place hormone

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receptive machinery and endpoints of their stimulation in identified, non-endocrine DA pathways, and could identify novel and important neural substrates for the independent modulation of functionally and physiologically distinct DA systems that are differentially important to sensorimotor and cognitive function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOW DOES ANDROGEN INHIBIT FETAL LUNG MATURATION Principal Investigator & Institution: Nielsen, Heber C.; Professor of Pediatrics; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2002; Project Start 01-JUL-1986; Project End 30-JUN-2004 Summary: (Adapted from the applicant's abstract) The goal of this application is to develop better understanding of the mechanism of fibroblast-type II cell communication which regulate the development of surfactant synthesis. The investigators have shown that the epidermal growth factor and its receptor (EGFR) control the initiation of this communication, while dihydrotestosterone (DHT) and transforming growth factor beta (TGF beta) inhibit it. Dr. Nielsen has recently gained new insight to the elements of this process, showing that other members of the EGF family are important to this process. He proposes to identify the molecular mechanisms of fibroblast-type II cell communication, including their positive and negative regulation. He hypothesizes that EGFR activation in fetal lung fibroblasts stimulates production of neuregulin (NRG) which activates ErbB-2 receptors on type II cells to stimulate surfactant synthesis. Furthermore, DHT and TGF beta inhibit this pathway. The Specific Aims to be tested are that 1) the mechanisms of fibroblast-type II cell communication are controlled by specific ErbB receptor expression , dimerization and trafficking in fetal lung fibroblasts and type II cells during development and identify which dimers in fibroblasts induce fibroblast-type II cell communication, and which dimers in type II cells stimulate surfactant synthesis; 2) EGF-R activation positively regulates fibroblast-type II cell communication by stimulating fibroblasts to produce NRG, which then induces surfactant synthesis. They will study the effect of upregulation and inhibition of EGF-R activation on NRG production, and inhibit NRG production to test if this removes the ability of EGF-R activation to induce fibroblast-type II cell communication; 3) DHT and TGFbeta down regulate specific elements of ErbB receptor activation and NRG production, disrupting fibroblast-type II cell communication. They will study the effects of DHT and TGFbeta on ErbB receptor expression and activation in fibroblasts and type II cells, on NRG production by fetal lung fibroblasts, and stimulation of surfactant synthesis in type II cells. These studies are expected to provide significant new insights to the mechanisms regulating surfactant synthesis in the fetal lung and make important contributions towards developing new strategies for preventing and treating RDS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HOXA 13 REGULATION OF GENITOURINARY DEVELOPMENT Principal Investigator & Institution: Stadler, H Scott.; Assistant Professor; Molecular and Medical Genetics; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2004 Summary: (adapted from the application) Nonsense mutations in the transcription factor Hoxa 13 result in severe malformations of the genitourinary (GU) region. In humans, loss of Hoxa 13 function causes familial hand-foot-genital syndrome (HFGS), resulting in hypospadia. prostate, uterine, Mullerian duct, vaginal bladder, ureter. and rectal defects. In mice, these developmental pathways are conserved, as targeted

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disruption of' Hoxa 13 results in malformation or agenesis of the prostate, uterus, urethra, ureter, MuIlerian ducts, vagina, rectum, and bladder. What is intriguing about the development of these structures is that many of them form from condensations of undifferentiated mesenchyme. Recently, I demonstrated that Hoxa 13 regulates mesenchymal condensation in the limb and umbilical vasculature (UV) by controlling genes that-direct cell-cell adhesion, apoptosis, and identity. Because many of the structures affected in HFGS are derived from mesenchymal condensations. I hypothesize that the genetic pathways regulated by Hoxal13, to mediate limb and UV development also function to direct normal development of the GU region. To test this hypothesis, a Hoxa 13 mutant mouse with an in-frame GFP reporter will be used. The Hoxa 13 GFP allele produces a strong, Hoxa 13-specific signal in the affected GU regions. This signal facilitates the enrichment of homogeneous populations of cells by fluorescence-activated cell sorting (FACS) from dissected tissues expressing Hoxa 13. Mesenchyme cells purified by FACS from the affected regions of mutant and control embryos will be characterized in vitro for changes in gene expression, cell adhesion, apoptosis, and proliferation that could account for specific malformations. These FACS enriched cells will also be used as a resource for RNA-and cDNA-based gene discovery methodologies to identify additional genes regulated by Hoxa 13 that play a role in GU development. Once identified, the chromosomal localization of Hoxa 13 specific target genes will be determined using mouse/hamster radiation hybrid DNA panels. The map positions and embryonic expression patterns of any newly identified genes will be made available to the research community, providing a resource to identify unknown genetic components involved in benign prostate hyperplasias, malignancies, and GU malformations. The epistatic relationship between Hoxa 13, and dhydroxytestosterone will be determined using a Hoxa 13 GFP reporter cell line in conjunction with in vitro screen, to identify genes that activate Hoxa 13. This unique experimental design allows study of GU development from the, perspective of the cells and tissues most affected by loss of Hoxa 13 function. From this perspective, insight genetic and cellular mechanisms required for normal GU development will be gained. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN PROSTATIC 3A HYDROXYSTEROID DEHYDROGENASE Principal Investigator & Institution: Lin, Hsueh-Kung; Urology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 28-SEP-1998; Project End 31-JUL-2005 Summary: (Adapted from the Applicant's Abstract): In androgen target tissues 3ahydroxysteroid dehydrogenases (3a-HSDs) may regulate the occupancy of androgen receptor (AR) by interconverting 5a-dihydrotestosterone (5a-DHT, a potent androgen) with 5a-androstane-3a,17b-diol (3a-diol, a weak androgen). We have obtained type 2 and type 3 3a-HSD cDNAs expressed in human prostate and overexpressed the enzymes in E. coli. Kinetic studies of these recombinant enzymes show that type 3 3aHSD functions as both a 3a-and 17b-HSD to inactivate active androgens, whereas, type 3 3a-HSD interconverts 5a-DHT with 3a- diol. Levels of 3a-HSD mRNA were higher in primary cultures of prostatic epithelial cells than stromal cells; and elevated levels of 3aHSD mRNA were observed in primary cultures of epithelial cells derived from benign prostatic hyperplasia and prostatic carcinoma tissues. Expression of steady state levels of 3a-HSD mRNA is up-regulated by epidermal growth (EGF) in human prostatic cell lines, LNCaP (androgen sensitive) and PC3 (androgen insensitive). The focus of this proposal is to examine the physiological functions of type 2 and type 3 3a-HSD in regulating androgen metabolism and their activities in modulating prostatic cell

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proliferation will be investigated. This will be accomplished by stably transfecting type 2 and type 3 3a-HSD cDNAs into these cells. Second, levels of endogenous type 2 and type 3 3a-HSD transcripts will be examined in RNA extracted from the cell lines and normal prostate using ribonuclease protection assay (RPA). Third, EGF-regulated type 2 and type 3 3a-HSD mRNA levels will be examined using RPA. Changes in 3a-HSD expression mediated by EGF will be examined in cell lysates by immunotitration of the enzyme activity. Fourth, to understand the constitutive and EGF- regulated type 2 and type 3 3a-HSD expression in prostatic cells, the 5'-flanking regions of the 3a-HSD genes will be sequenced and cis-acting elements responsible for transcription regulation of two isoforms will be identified. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMAGING THE IN VIVO ANTI-TUMOR EFFECTS OF ANSAMYCINS Principal Investigator & Institution: Rosen, Neal; Sloan-Kettering Institute for Cancer Res New York, Ny 100216007 Timing: Fiscal Year 2002 Summary: The objective of this proposal is to image the responses of tumors to new chemotherapeutic drugs in animals, while they are undergoing experimental treatment, and to develop new noninvasive imaging methods to assess the molecular/biochemical effects on the pathways these drugs were designed to inhibit, at doses that are tolerable in animals. This proposal describes a pilot program for the achievement of these goals. We will specifically use animal models for breast and prostate cancer to study the antitumor effects of a drug derived from geldanamycin; namely, 17allylarninogeldanamycin (17-AAG). We will use PET scanning with [18F]fluorodeoxyglucose (FDG) and [124I]-iododeoxyuridine (IUdR) to image the tumor response to the drug, and [18F]-dihydrotestosterone (FDHT) to image changes in the androgen receptor. Effects on glucose utilization and tumor proliferation will be correlated with changes in the physical size and pathological markers of tumor response; in prostate xenografts (LNCaP), androgen receptor imaging with FDHT will also be performed. In collaboration with Project 1 of this P-50 application, we will attempt to image loss of HER2-SHC interactions and inhibition of Ras-dependent signaling by the drug. These results will be correlated with direct measurements of HER2, steroid receptor and Raf degradation and downregulation of D cyclin expression in pathologic specimens. A second objective is to evaluate the use of imaging in determining drug response and to develop methodologies to image inhibition of specific signaling pathways. If successful, these techniques will become an integral component of the preclinical development of the drugs we are studying. It is important to note that the animal imaging studies in Aims 1 and 3 of this proposal are complementary to the imaging studies that will be performed on patients with advanced metastatic prostate cancer, as proposed in Project 4 of this P-50 application. In both projects, one objective is to obtain metabolic (phenotypic) images in order to assess and better understand the progression and response of cancer to new molecular-based treatment modalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNOLOGICAL ASPECTS OF HEMORRHAGE Principal Investigator & Institution: Chaudry, Irshad H.; Professor, Professor, Vice Chairman & Di; Surgery; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-APR-1988; Project End 31-MAR-2007

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Summary: (provided by applicant): A major feature of trauma is immune depression. Studies demonstrate immune depression is severe in aged and ovariectomized (OVX) females and adult males, as opposed to maintained immune functions in proestrus females, after trauma-hemorrhage and resuscitation (T-H). Administration of 17betaestradiol (E2) in OVX females and males, or prolactin or steroid enzyme activity modulators (SEAM) in males after T-H restores immune functions. Moreover, survival rate of proestrus females subjected to sepsis after T-H is significantly higher than agematched males or OVX females. Studies also show that increased 5alphadihydrotestosterone synthesis in T cells is the likely cause for immune depression in males, while continued E2 synthesis maintains immune functions in proestrus females, following T-H. Similarly, hypoxemia also causes immune depression in mice. Recent studies show that in males, (a) pattern recognition receptors TREM 1, 2 and 3 are expressed in CD11b+ macrophages from bone marrow, PBMC, spleen and liver, in the absence of LPS stimulation, and their expressions are enhanced following T-H, and (b) there is a Th1 to Th2 shift in T cell cytokine release following T-H, implying that the depression in immune function may be due phenotypic changes in MPh and T cells. Since immune response following T-H is gender-dimorphic, phenotypic changes occurring in the immune cells early following T-H may be different in males and proestrus females. Therefore, the hypothesis is that the sex steroid hormonal milieu prevailing at the time of injury induces phenotypic changes in macrophages and T cells whose altered functions, evidenced in the release of mediators, lead to either depression or maintenance of immune functions after T-H. Since macrophages and T cells express receptors for sex steroids, and T cells synthesize active steroids in situ, it is also hypothesized that modulation of immune functions early following T-H with sex steroid receptor-specific antagonists/agonists or SEAM will lead to restoration and maintenance of immune functions and decrease mortality from subsequent sepsis in both genders. The specific aims are to: characterize phenotypic changes in macrophages and dendritic and T cells in the inflammatory microenvironment early following T-H; delineate the mechanism(s) for the release of inflammatory mediators by immune and endothelial cells; determine the contribution of hypophysis-pituitary-adrenal-gonad axis to immune depression; and evaluate the effects of steroidogenic enzyme and sex steroid receptor-specific modulators for restoring immune functions in males and estrus cyclespecific females after T-H or hypoxemia. Detailed analysis of phenotypic changes in immune cells and understanding their functions in T-H induced milieu, using recent cellular/molecular biological techniques, delineating sex steroid immune functions and assessing how they can be modulated by exogenous steroidal/ nonsteroidal modulators to improve immune responses should lead to innovative approaches for preventing immune depression and reducing mortality from sepsis in trauma victims with low E2 levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPACT OF PUBERTY ON THE KIDNEY IN DIABETES Principal Investigator & Institution: Lane, Pascale H.; Associate Professor; Pediatrics; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The prepubertal years of type 1 diabetes (DM) appear to be protected from expression of nephropathy and other microvascular complications. Only post-pubertal male rats given the diabetogenic agent streptozocin (STZ) develop renal and glomerular hypertrophy associated with increased expression and activity of transforming growth factor b (TGFb). Prepubertal rats do not develop

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hypertrophy or upregulation of the TGF system. Given clinical differences in the prevalence and rate of progression between the sexes, gonadal steroids seem likely to be involved in these processes. Overall hypothesis: Androgen synthesis that accompanies puberty contributes to the development of diabetic nephropathy via changes in the renal transforming growth factor (TGF(3) system. Specific Aims: I) What are the roles of androgens in diabetic kidney disease? 1)Examine sex differences in the renal reponse to STZ DM; 2)Examine the effects of gonadectomy on the post-pubertal renal response to STZ DM; 3)Determine the effect of testosterone treatment on the renal response to STZ DM; 4)Determine the role of the androgen receptor in the renal response to DM; and 5)Determine whether conversion to dihydrotestosterone is necessary for the postpubertal renal response to STZ DM. II) What is the mechanism through which puberty promotes TGFfi expression/activation? 1 )Examine the renin-angiotensin system in response to pre- and post-pubertal states and hormonal manipulation; 2)Examine the protein kinase C system in response to pre- and post-pubertal states and hormonal manipulation; 3)Examine the oxidative stress system in response to pre- and postpubertal states and hormonal manipulation; 4)Define the direct effects of sex steroids in vitro on the oxidative stress pathway; and 5)Define the direct effects of sex steroids in vitro on the PKC pathway. Methods: Rats will be given STZ DM pre- or post-puberty for 6 weeks, a duration of DM which increases TGFI3 expression and renal weight in adults. Groups will include males and females with and without earlier gonadectomy. Some groups will also receive treatment with testosterone, flutamide, an androgen receptor blocker, or finasteride, which blocks conversion of testosterone to dihydrotestosterone. in vitro studies will involve kidney slice cultures from 10 week old castrated male rats, with or without prior induction of OM. Media will include normal or high glucose conditions, as well as variable amounts of testosterone or estrogen. Measurements will include TGFJ3 proteins by ELISA and nitric oxide synthase isoforms, angiotensin II receptor, and protein kinase C isoforms by immunoblotting; superoxide generation; nitric oxide synthase activity; protein kinase C activity; mRNA for TGFb, nitric oxide synthases, and TGFb inducible gene-H3 by RT-PCR; plasma and renal levels of angiotensin II; and blood levels of sex steroids by RIA. Health implications: New treatments to prevent diabetic kidney disease, the most important cause of kidney failure in the US, may emerge from a better understanding of a naturally protected state such as the prepubertal animal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INDUCTION OF AR TRANSACTIVATION BY DHT AND E2 Principal Investigator & Institution: Chang, Chawnshang; Professor; Pathology and Lab Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (Provided by the applicant) Androgens, acting through the androgen receptor (AR), mediate a wide spectrum of developmental and physiological processes, including the development and maintenance of the prostate. However, it has recently been shown that AR can be transcriptionally activated in vitro by 17(3-estradiol (E2) in the presence of the AR coregulator ARA70. In rodent models, neonatal exposure to exogenous estrogen results in a dose dependent alteration of adult prostate size and histology. However, targeted disruption of the estrogen receptors (ER) a and P in mice do not conclusively show a role for either ER in prostate development, potentially indicating that exogenous estrogens may be acting at least in part through AR to influence prostate growth. Estrogens and androgens are structurally similar with the major difference occurring at the C-3 position of the steroidal A-ring where

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dihydroxytestosterone (DHT) carries a keto group and E2 carries a phenolic hydroxyl. To investigate the amino acid residues of AR that mediate the ability of E2 to induce AR transcription, and the mechanism through which coregulators differentiate between DHT- and E2-bound AR, we propose in Specific Aim I to isolate mutations of AR that transcriptionally respond to DHT but not E2. In Specific Aim 2, we will isolate AR mutants the preferentially respond to E2. In Specific Aim 3, we will isolate specific coregulators that differentially interact with DHT- or E2-bound AR. In Specific Aim 4, we will determine the mechanism of DHT or E2 induced transcription of AR in the presence of AR coregulators. Finally, in Specific Aim 5 we will determine the effect of E2 induction of AR transcription in prostate cells. The success of this proposal will not only allow us to understand how E2 regulates AR transcription, but will also provide information on transcription by AR in response to different ligands, which may ultimately lead to novel therapeutic approaches to prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHIBITORS OF 5ALPHA-REDUCTASE FOR ACNE THERAPY Principal Investigator & Institution: Li, Lingna; Anticancer, Inc. 7917 Ostrow St San Diego, Ca 92111 Timing: Fiscal Year 2002; Project Start 20-JUN-2002; Project End 31-MAY-2003 Summary: This application addresses the need for selective non-toxic for acne. Excessive 5alpha-reductase activity is found in acne vulgaris as well as androgenic alopecia (male pattern baldness). Numerous side effects occur from current treatments of these diseases both of which originate in the pilosebaceous unit. We have developed a selective, effective, topically applied 5alpha-reductase inhibitor to modify pathological processes in the pilosebaceous unit. For example, toward this goal, we have previously developed a selective topical liposome hair follicle targeting technology fo r genes and other large and small molecules. The present application will focus on our recent observation that the 5-alpha- reductase inhibitor N, N-diethyl-4-methyl-3-oxo-4-aza-5alpha- androstane17beta-carboxamide (4-MA) incorporated into liposomes selectively induces apoptosis and inhibits growth of the dihydrotestosterone (DHT)-dependent hamster flank organ sebaceous gland. With regard to selectivity, when non-liposomal 4-MA was topically applied, the selective efficacy was lost resulting in the on- targeted contralateral gland being affected. With regards to safety, liposome 4-MA did not significantly affect prostate weight, T/DHT ratios or body weight gain compared to controls indicating safety as well as efficacy of topical application of liposome 4-MA. We proposed here to develop topical liposomal 4-MAS as an anti-acne agent. The Specific Aims of this application are as follows: 1) Optimize efficacy of topical liposomal 4-MA to selectively induce apoptosis of sebaceous glands of male hamsters; 2) Determine pharmacokinetics of topical liposomal 4- MA to hair follicles of human scalp grafted into SCID mice and in the hamster sebaceous gland; 5) Determine safety of effective doses of liposomal-4-MA by detection of changes in DHT/T blood ratios in treated animals. In Phase II, selective efficacy and safety studies will be conducted on larger animals in order to enable liposomal 4-MA to enter the clinic as an anti-acne therapeutic. PROPOSED COMMERCIAL APPLICATIONS: Liposomal 4-MA will be developed as a topical selectively targeted therapeutic for acne for which they should be a very market. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INSULIN RESISTANCE IN CHILDHOOD Principal Investigator & Institution: Arslanian, Silva A.; Professor; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 152132583

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Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 30-APR-2005 Summary: (Adapted from the Applicant's Description) This application is for a Midcareer Investigator Award in Patient-Oriented Research for Silva Arsianian, M.D., Associate Professor of Pediatrics University of Pittsburgh, Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Children s Hospital of Pittsburgh. The award will serve two purposes: (1) to assist the principal investigator to further develop her research endeavors in investigating insulin resistance in childhood; and (2) more importantly, to provide her with protected time to mentor the future generation of clinician- scientists in patient-oriented research (POR) by providing state-of-the-art clinical research in the multiple aspects of pediatric metabolism and diabetes. Cardiovascular disease is the leading cause of death in the United States. A growing body of evidence points to insulin resistance and the cardiovascular dysmetabolic syndrome (hyperglycemia, hyperinsulinemia, hyperlipidemia and hypertension) as a major risk factor. Dr. Arsianian's research has focused on investigating insulin resistance in childhood with the objective of early intervention/prevention to improve overall health outcome in adulthood. The principal investigator's POR is to investigate hormonal, metabolic, nutritional and environmental causes of insulin resistance in children. For the K24 award the focus of research will be: (1) to continue to investigate racial (Black/White) differences in insulin sensitivity and metabolic partitioning of fat in an effort to determine childhood risk factors for the higher rates of obesity, Type 2 diabetes and CVD in African-Americans; (2) to assess, longitudinally, the effects of dihydrotestosterone (DHT), a nonaromatizable androgen in prepubertal boys to determine the role of androgen vs growth hormone in insulin resistance of puberty; and (3) to investigate the relationship of hyperinsulinemia and hyperandrogenenua, crosssectionally and longitudinally, in female children with hyperandrogenisnt The clinical research tools include insulin-glucose clamp experiments, stable isotope methodologies, indirect calorimetry, assessment of body composition and body fat topography, assessment of physical fitness and activity and assessment of free-living energy expenditure. Future directions in POR include: (1) Family- based behavioral lifestyle treatment of pediatric obesity; (2) multi center investigation of the emerging epidemic of obesity-related Type 2 diabetes in children, especially African-American and Latino; (3) development of noninvasive methods, p31 NMR spectroscopy to study muscle energy metabolism in children; (4) intervention/prevention strategies for childhood obesity. Early identification in childhood of precursors of adult morbidity will form the basis to fulfill the objectives of "Healthy People 2000." The mentoring component of this award will insure that the new generation of clinician- scientists will be fully prepared for an academic/investigative career in POR in pediatrics to carry to the next millennium Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANDROGENS

MALE

PSEUDOHERMAPHRODITISM--THE

BIOLOGY

OF

Principal Investigator & Institution: Imperato, Julianne; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MALE REPRODUCTIVE EFFECTS FROM EXPOSURE TO BORON Principal Investigator & Institution: Robbins, Wendie A.; Assistant Professor; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 29-SEP-2006 Summary: This is an epidemiologic study that will investigate the relationship between workplace exposure to boron containing compounds (including boric acid, borax) and adverse male reproductive effects. Boric acid has been identified as one of the highest priority chemicals for human field study by Moorman et al. (2000) in their review of 43 National Toxicology Program reproductive toxicants. Prioritization was based on the strength of animal data, estimated numbers of humans exposed in the workplace, and lack of adequate reproductive health effects data for the human. Animal studies show boric acid has effects on male reproduction at comparatively lower doses than other known reproductive toxicants, reproductive system sensitivity over other toxicities, and a probable threshold for adverse effects. Three human studies have published results on reproductive effects of occupational boron exposure. Two found no effect on fertility or development and one found testicular atrophy and sterility. All three have been criticized for study design issues or lack of adequate exposure assessment. A need still exists for a definitive human reproductive study. Therefore, the specific aims of this research are to: (1) Describe the relationship between boron exposure and direct measures of toxicity on male reproduction: total sperm count, sperm density, viability, motility, morphology, and sperm X:Y chromosome ratios sperm chromatin integrity measured by sperm chromatin structure assay (SCSA), COMET, TUNEL, protamine 1 (P1), protamines 2-4 (HP2-4), and protamine 2 precursor proteins (HPI1-2, HPS1-2) in ejaculated sperm cells; blood and urine steroid hormone markers including testosterone, free testosterone, serum hormone binding globulin, dihydrotestosterone, LH, FSH, estrone, estradiol, estriol; (2) describe the relationship between boron exposure and indirect measures of toxicity on male reproduction: fertility history and physical exam data; and (3) describe the relationship between workplace, environmental, and dietary sources of boron with biomarkers of exposure and reproductive effect. The goal is to contribute critical information on the exposure level at which boron causes adverse effects on human male reproduction. The information could then be used to inform workplace practices and policies to protect the reproductive health of the hundreds of thousands of men estimated to be exposed to boric acid and other boron containing compounds in the workplace. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF ANDROGEN-MEDIATED INHIBITION OF ADIPOGENESIS Principal Investigator & Institution: Singh, Rajan; Charles R. Drew University of Med & Sci 1731 East 120Th Street Los Angeles, Ca 900593025 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: The overall objective of this pilot project is to investigate the role of androgens during adipogenic differentiation using in-vitro as well as in vivo models of adipogenesis, and understand the possible mechanisms by which androgens may regulate the fat cell formation. Android obesity, an important risk factor for cardiovascular diseases occurring at disproportionately high rates in racial/ethnic minorities, is characterized by excessive accumulation of adipose tissue in abdominal and visceral regions. Clinical studies using Testosterone (T) has suggested its beneficial

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role in men, with a significant increase in fat-free mass. However, the mechanisms by which T or its metabolite dihydrotestosterone (DHT) inhibit fat cell formation is largely unknown. In this project, we will study the adipogenic differentiation of pluripotent and preadipocyte cell lines and the possible roll of androgens in modulating the common differentiation pathway of these cells into adipogenic lineage. We will test the presence of androgen receptors in our cell system and focus our studies on the effects of androgen on the key transcription factors C/EBPalpha and PPARgamma2, which are necessary and sufficient to induce adipogenesis. We will examine the mRNA and protein expression of these factors using RT-PCR, western blot and immunohistochemistry. The fat cell formation will be quantitated using Oil-Red O staining. The possible intermediate role of Wnt signaling pathway, a molecular switch that governs adipogenesis, will be investigated during androgen mediated inhibition of adipogenesis. We will test whether inhibition of Wnt signaling using pharmacological as well as retroviral approaches blocks the anti-adipogenic potential of androgens. We will generate an in vivo model of adipogenesis by injecting 3T3-F442 preadipocyte cell line in athymic mice and study the effect of different doses of T and DHT on the formation of fat pads. The expression of adipose specific mRNAs and proteins like C/EBPalpha, PPARgamma2 and 422/aP2 will be quantitated and analyzed to examine the antiadipogenic role of androgens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF INCONTINENCE FOLLOWING VAGINAL DISTENSION Principal Investigator & Institution: Damaser, Margot S.; Research Biomedical Engineer; Urology; Loyola University Chicago Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 05-APR-2000; Project End 31-MAR-2005 Summary: (Adapted from Applicant's Description): One of the most common symptoms of pelvic floor dysfunction is Stress Urinary Incontinence (SUL), the leakage of urine with increased stress, such as during laughing or coughing. The epidemiologic factors most strongly associated with the development of SUI are vaginal delivery and advanced age. In addition to other contributing factors, there is clinical evidence that the pudendal nerve is damaged during vaginal delivery and that women with SUI have greater nerve damage. Decrease in concentrations of circulating gonadal steroid hormones may be a precipitating factor for post-menopausal development of SUL. The long term goal of this project is to develop novel clinical methods for enhancing recovery of patients with SUL. Specifically, the neuro-anatomical and functional effects of vaginal distension will be investigated as well as the role of steroid hormones in enhancing recovery from incontinence. The hypotheses to be tested are 1. Vaginal distension causes traumatic injuries, including injury to the distal pudendal nerve, and leads to development of SUI, and 2. Treatment with gonadal steroid hormones will accelerate pudendal nerve regeneration and will lead to accelerated functional recovery of SUI after vaginal distension. These hypotheses will be tested by 4 Specific Aims: SAl. Demonstration that vaginal distension leads to incontinence symptoms followed by recovery, SA2. Demonstration that the SUI and recovery that results from vaginal distension is associated with a specific pattern of neural damage and regeneration, SA3. Determination if treatment with estrogen reduces the severity of and/or accelerates recovery from incontinence symptoms and nerve damage after vaginal distension, and SA4. Determination if treatment with dihydrotestosterone reduces the severity of and/or accelerates recovery from incontinence symptoms and nerve damage after vaginal distension. These Specific Aims will be tested in an established animal model of

34

Dihydrotestosterone

vaginal distension by urodynamic testing, histological evidence, and 3u tubulin mRNA levels in pudendal motoneurons determined using in situ hybridization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF SEX-DETERMINED RESISTANCE TO L. MEXICANA Principal Investigator & Institution: Satoskar, Abhay R.; Assistant Professor; Microbiology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: Sex hormones have been shown to have a profound influence on modulation of immune responses and the outcome of various diseases in males and females. We have found that female mice are relatively more resistant visceral and cutaneous leishmaniasis than the male mice. In the L. mexicana model, we found that female DBA/2 mice mount an efficient Th1-like response and develop smaller lesions than the male mice that develop large, non-healing lesions. Moreover, we also found that ovactomized female DBA/2 mice treated with dihydrotestosterone (DHT); a derivative of testosterone that can not be converted to estradiol, become susceptible to L. mexicana whereas castrated male mice treated with 17-beta-estradiol become resistant. These findings suggest that while estrogen plays a critical role in induction of protective immunity against L. mexicana, testosterone may be detrimental. Despite these findings it is not clear how sex hormones (estrogen and testosterone) regulate immune responses during L. mexicana infection. Our long term goal is to understand the immunological mechanisms responsible for gender dimorphism in susceptibility of mice to different Leishmania species. In this project, we propose to determine how these sex hormones (estrogen and testosterone) regulate in vivo immune responses and influence the outcome of cutaneous leishmaniasis caused by L. mexicana. The first specific aim would determine how estrogen induces the development of protective immunity against L. mexicana. The studies proposed in the second specific aim would determine how testosterone prevents development of protective immune response and mediates susceptibility to L. mexicana. The third specific aim will focus on studies using bone marrow chimeras to determine whether endogenous sex hormones regulate functional development of T cells in vivo and affects their ability to differentiate into Th1 or Th2 subsets The experiments proposed in this project are designed to investigate several potential mechanisms of the protective effects of estrogen (17-beta-estradiol) and the susceptibility-inducing effects of testosterone. We hypothesize that each hormone will act through a subset of the proposed mechanisms. We hope to identify immune mechanisms that are specifically modulated by each. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: METABOLIC EFFECTS OF STEROID HORMONES IN OBESE MEN Principal Investigator & Institution: Herbst, Karen L.; Assistant Professor; Internal Medicine; Charles R. Drew University of Med & Sci 1731 East 120Th Street Los Angeles, Ca 900593025 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2008 Summary: (provided by applicant): Obese men have comorbid conditions including insulin resistance, dyslipidemia and cardiovascular disease. They also have lower testosterone (T) levels than non-obese men. Administration of T to abdominally obese men with low-normal T levels by one group increased insulin sensitivity and decreased visceral fat. Cardioprotective high-density lipoprotein cholesterol (HDL-C) however,

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decreased, suggesting that developing selective androgen receptor modulators (SARMs) that are neutral to, or improve the lipid profile are required if T is to be considered a treatment for obesity. This is a prospective, randomized, double-blind trial to determine the effects of T and its metabolites, estradiol (E2) and 5alpha-dihydrotestosterone (DHT) on insulin sensitivity, body composition and lipid metabolism in obese men with low or low-normal T levels. Men between the ages of 21 and 50 years with a body mass index greater than 30 kg/m2, waist measurement greater than 100cm and a waist-to-hip ratio greater than 1.0 will have T clamped within the normal range using a gonadotropin releasing-hormone (GnRH) antagonist and exogenous T except in the placebo group. Sixty subjects will be randomized into one of 4 groups: 1) Placebo group; 2) T alone group- GnRH antagonist + exogenous T + oral placebo; 3) Aromatase inhibitor groupGnRH antagonist + T + anastrazole; and 4) 5alpha-reductase inhibitor group - GnRH antagonist + T + dutasteride. Group 3 will examine outcomes in the absence of E2 while group 4 will examine outcomes in the absence of DHT. Insulin sensitivity by the frequently-sampled intravenous glucose tolerance test, total fat by dual-energy X-ray absorptiometry, regional fat including subcutaneous, visceral and intermuscular fat by magnetic resonance imaging, and intramyocellular fat by 1H-nuclear magnetic resonance spectroscopy will be examined before and after treatment. Fat and muscle biopsies will be obtained before and after treatment to examine tissue-specific insulin sensitivity and to begin an analysis of altered gene expression as it pertains to insulin sensitivity. Lipid metabolism will be examined in detail before and after treatment to include HDL-C, lowdensity lipoprotein size and activities of hepatic lipase, lipoprotein lipase, cholesteryl ester transfer protein and phospholipid transfer protein. These outcomes should begin to describe steroid hormone effects on important metabolic outcomes important for the development of SARMs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS OF SEX STEROID ACTION IN PROSTATE CANCER Principal Investigator & Institution: Zhu, Yuan-Shan; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2006 Summary: (provided by applicant): Prostate cancer is a leading cause of cancer death in American males. The major medical therapy for metastasized prostate cancer includes various regimens of androgen ablation. Androgens especially dihydrotestosterone (DHT) play a critical role in prostate development, growth and pathogenesis of benign prostate hyperplasia and prostate cancer. In the prostate, the action of androgen can be modulated by estrogen. Both androgens and estrogens display their action via their corresponding androgen receptor (AR) and estrogen receptors (ERs), respectively. Currently, one AR and two ERs, ERalpha and ERbeta, have been identified. The two ERs may possess differential effects in mediating estrogen actions. In pilot studies, we have found that DHT was the major androgen to induce prostate growth and prostate specific antigen gene expression. Interestingly, DHT action was modulated by estrogen in a receptor-isoform and ligand specific manner. 17alpha-estradiol was anti-androgenic and anti-growth in prostate tumor cells. Thus, we'll further explore in greater detail the effects of estrogen analogs on the modulation of DHT actions and prostatic tumor cell growth using in vitro and in vivo models to test the hypothesis that the effects of estrogens are ER-isofrom and ER-ligand specific, and 17alpha-estradiol is a potential agent for prostate cancer therapy. The ER-isoform specificity of estrogen action on modulating DHT-induced PSA gene expression will be determined in prostatic tumor

36

Dihydrotestosterone

LAPC-4 cells, and the effects of different ER-ligands compared. The ERisoform specificity will be further analyzed in ERalpha and ERbeta knockout animals, and in prostatic tumor LAPC-4 cells using antisense technology. By comparing the effects of various ER-ligands on regulating prostate cancer cell growth and proliferation in cell culture and in animal models, the ligand specificity of estrogen action will be determined. The anti-androgenic and antitumor effects of 17alpha-estradiol will be further explored in cell culture and in a xenograft animal model of prostate cancer. Elucidation of receptor-isoform and ligand specificity of estrogen-androgen interaction will facilitate our understanding of sex-steroid interaction in prostate physiology and pathogenesis, and the development of specific ER-ligands for the treatment of androgendependent and androgen-independent prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR DETERMINANTS OF ANDROGEN RECEPTOR PHARMACOLOGY Principal Investigator & Institution: Mcdonnell, Donald P.; Professor; Pharmacology and Cancer Biology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Until recently the molecular pharmacology of the human androgen receptor (hAR) was considered to be relatively simple. Compounds like dihydrotestosterone (DHT) functioned as agonists by binding to and inducing a change in receptor structure. This activating conformational change initiated a series of events that led to the interaction of the receptor with specific DNA sequences within target genes. In the DNA bound state the receptor was able to couple with the proteins and processes required for its transcriptional regulatory activities. In these established models of AR action, antagonists were believed to function solely by competitively inhibiting the interaction of agonists with the receptor. However, as with other receptors, notably the estrogen, progesterone and glucocorticoid receptors, the pharmacology of AR is now believed to be more complex and in general appears to be a function of (a) the expression level of the receptor, (b) the effect of the bound ligand on receptor structure, (c) the ability of differently conformed ligand-receptor pairs to engage coactivators and corepressors and (d) the relative expression level of coactivators and corepressors in different cells. In this grant we propose a series of studies with the objective of defining how information flows from an AR ligand to its receptor and subsequently to target genes. This will be accomplished in a study with three specific aims; (1) Identification of surfaces exposed on AR in the presence of different ligands (2) Definition of the functional significance of the surfaces on AR implicated by the peptide binding studies and (3) Identification of the proteins that interact with functionally important surfaces on AR. It is anticipated that at the conclusion of these studies we will have a better understanding of the molecular mechanism of action of the currently available AR agonists and antagonists. In addition these studies may suggest ways to exploit the complexity of the AR signaling pathways for the development of Selective Androgen Receptor Modulators (SARMs) for use in the treatment of a variety of androgenopathies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PH II & III: (DHT) GEL FOR HORMONAL REPLACEMENT HYPOGONADAL MEN Principal Investigator & Institution: Weber, Thomas J.; Duke University Durham, Nc 27710

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Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SECRETION

PROGESTERONE

MODULATION

OF

PULSATILE

GNRH

Principal Investigator & Institution: Mccartney, Christopher R.; Center for Res in Reproduction; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): This Research Career Award will support the development of Christopher R. McCartney, M.D., of the University of Virginia (UVa) as he continues to train in patient-oriented research under the mentorship of John C. Marshall, M.D., Ph.D., a renowned researcher in the fields of reproductive neuroendocrinology and the polycystic ovary syndrome (PCOS). This training will allow Dr. McCartney to acquire the knowledge and skills needed by an independent clinical researcher. To this end, the application outlines a career development plan that includes comprehensive instruction in clinical trials methodology, biostatistics, epidemiology, research ethics, assay methodology, and hormone pulse analysis; this will occur in part through the Master of Science Program in the UVa Dept. of Health Evaluation Sciences. Dr. McCartney's research proposal is designed to enhance understanding of the etiology of neuroendocrine abnormalities in PCOS, a very common but enigmatic disorder marked by hyperandrogenism, ovulatory dysfunction, and decreased fertility. Although the etiology of PCOS is unknown, relative gonadotropin-releasing hormone (GnRH) pulse generator resistance to negative feedback by progesterone (P) and estradiol (E2) contributes to a persistently rapid luteinizing hormone (LH) pulse frequency, ovulatory dysfunction, and hyperandrogenemia. GnRH pulse generator resistance to negative feedback may also be present in adolescents with hyperandrogenemia, felt to be a forerunner of adult PCOS; this would, in part, explain the pubertal genesis of abnormal LH secretion in adolescents destined to develop PCOS. The specific goals of this research are to delineate the relative roles of P and E2 in the regulation of the GnRH pulse generator throughout ovulatory menstrual cycles; to elucidate the potential role of P in directing diurnal changes of LH (and by inference GnRH) pulsatility in peripubertal adolescent girls; and to define abnormalities of gonadal steroid feedback on the GnRH pulse generator in hyperandrogenemic adolescents and in adults with PCOS. The research will be performed in a state-of-the-art General Clinical Research Center at UVa and, in conjunction with didactic training in scientific inquiry and data analysis, will permit Dr. McCartney's development into an independent patient-oriented investigator in the field of reproductive endocrinology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSTATE CANCER PREVENTION TRIAL Principal Investigator & Institution: Paskett, Electra D.; Professor and Associate Director of Popu; Wake Forest University 1834 Wake Forest Road Winston-Salem, Nc 27106 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PUBERTAL ORGANIZATION OF BRAIN AND BEHAVIOR Principal Investigator & Institution: Sisk, Cheryl L.; Professor and Director; Microbiology and Public Health; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): During human adolescence the brain undergoes a profound remodeling that is both sculpted by gonadal steroid hormones and associated with the emergence of sex-biased psychopathologics such as anorexia nervosa, depression, and schizophrenia. Because puberty is a period of extraordinarily rapid change in the nervous system, the brain may be particularly vulnerable to perturbations in the timing of interactions between hormones and developmental trajectory. The normal timing of these interactions in human adolescents is altered by anabolic steroid use, by the increasingly earlier onset of gonadal puberty in girls, and by the delay in gonadal maturation induced by eating disorders, extreme exercise, or disease. The overall goal of this research is to determine how the timing of interactions between the rapidly developing adolescent brain and gonadal steroid hormones influences individual differences adult behavior and nervous system structure. Using a rodent model, we've found that the absence of gonadal hormones during pubertal brain development adversely affects the expression of male social behaviors in adulthood. These behavioral compromises are long-lasting, and are not reversed by testosterone replacement in adulthood, indicating that the timing of exposure to steroid hormones determines adult responses to hormonal and sensory stimuli. The specific aims of the proposed work are to 1) test the hypothesis that capacity for testosterone-dependent organization of reproductive behavior varies over prepubertal, pubertal, and postpubertal development; 2) discover whether androgenic or estrogenic actions of testosterone mediate testosterone-dependent organization of neural circuits and behavior during puberty; and 3) test the hypothesis that steroid-dependent pubertal organization of male reproductive behavior is associated with enduring structural modifications within the neural circuit mediating the behavior. The strategy will be to vary the postnatal age at which male hamsters are exposed to a three week period of androgen or estrogen (either before, during, or after puberty), and then assess behavior and structural characteristics in adulthood. This research integrates neuroanatomy, endocrinology, and behavior, and will establish new and fundamental principles of developmental neurobiology and psychobiology that are directly relevant to human development and mental health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF A PROSTATE SPECIFIC GENE: UGT2B17 Principal Investigator & Institution: Grant, Delores J.; North Carolina Central University 160 Alexander-Dunn Bidg. Durham, Nc 27707 Timing: Fiscal Year 2002; Project Start 01-JUN-1977; Project End 31-DEC-2005 Summary: The health and normal survival of steroid target tissues is dependent on exposure to adequate levels of steroid hormones. Thus, normal function of the prostate, a steroid target tissue, is dependent on exposure of that organ to adequate levels of male specific steroids, hormones or androgens. Conversely, exposure to extremely high levels of androgens is believed to contribute to malignant transformation of prostate tissue, already the leading cause of cancer-related deaths in the United States. Androgen levels within steroid hormone target tissues such as the prostate are thought to be regulated at least in part by the catabolism of that steroid by UDP-Glucuronosyltransferase 2B17

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(UGTB17). Evidence supporting this hypothesis comes from numerous studies demonstrating that the UGT2B17 enzyme reacts with or glucuronidates androgens such as testosterone, dihydrotestosterone, and androsterone. Thus, the UGT2B17 enzyme is important to the catabolism and elimination of androgens by glucuronidation and consequently impacts the levels of circulating steroid in target tissue such as the prostate. The overall aim of this research is to test the hypothesis that aberrant expression of this gene may alter the risk for prostate cancer and that the gene may ultimately be a genetic susceptibility marker for prostate cancer. Towards that goal, it is proposed that the alterations in the gene expression of the UGT2B17 gene by DNA methylation and single nucleotide polymorphisms (SNPs) subsequently impact the normal function and structural integrity of androgen-dependent tissue. Towards that goal, it is proposed that the alterations in the gene expression of the UGT2B17 gene by DNA methylation and single nucleotide polymorphisms (SNPs) subsequently impact the normal function and structural integrity of androgen-dependent tissue. The experiments in this proposal will determine if DNA methylation is 1) altered in the gene promoter of the UGT2B17 gene expressed in a human prostatic carcinoma cell line, LNCaP, in the presence of growth factors that are normally present in the prostate microenvironment 2) altered in other cells of various tissue origin and 3) impacted by the presence of SNPs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF ANDROGEN RECEPTOR ACTIVITY IN THE PROSTATE Principal Investigator & Institution: Garabedian, Michael J.; Microbiology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from the application) Our broad, long term objective is to characterize the molecular mechanisms by which the androgen receptor (AR) regulates transcriptional activation through its N-terminus. The AR is a hormone- dependent transcription factor involved in the regulation of both normal and malignant prostate cell growth. Although androgen hormones, such as dihydrotestosterone (DHT), act as the primary signal in activating AR's transcriptional regulatory functions, AR-mediated transcriptional activity is also controlled by associations with, as yet, unidentified regulatory cofactors involved in transcription. The N-terminus of AR contain several transcriptional activation functions, including AF-1a and AF-1b, and mutations in these domains reduce AR-dependent transcriptional activity. We propose that these domains provide surfaces that permit protein-protein contacts between the AR N-terminus and cofactors involved in transcriptional regulation. We propose that these domains provide surfaces that permit protein-protein contacts between the AR N-terminus and cofactors involved in transcriptional regulation. We will identify proteins that interact with the AR N-terminal activation domains using a modified yeast two-hybrid approach that is capable. Of isolating proteins that interact with transcriptional activators. We will also define the effect of these AR-interact with transcriptional activators. We will also define the effect of these AR-interacting proteins on AR- transcriptional activity using a transient transfection proteins on AR- transcriptional activity using a transient transfection system designed to monitor AR-dependent transcriptional activation in cultured mammalian cells. Conceivably, alterations in the level of these AR N-terminal interacting proteins modulate AR activity., thereby, contributing to malignant ARdependent prostate growth if altered in cancer. To test this hypothesis we will determine if the concentration of specific AR- interacting proteins varies in models of

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Dihydrotestosterone

benign and malignant prostate growth using antibody and nucleic acid probes. Understanding of the communication between AR and the proteins that associate with the AR N-terminal transcriptional activation domain is fundamental to understanding the mechanism of AR-regulated gene expression and may reveal novel points of intervention to be exploited in the development of new therapies for AR-dependent malignancies, such as prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF HUMAN PROSTATE EPITHELIAL CELL GROWTH Principal Investigator & Institution: Ware, Joy L.; Professor; Pathology; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 18-MAY-1998; Project End 28-FEB-2006 Summary: (provided by applicant): Two diseases of the prostatic epithelium, benign prostatic hyperplasia (BPH) and prostate cancer, are among the major health problems faced by American men. Deregulation of prostatic epithelial cell proliferation is a central event in both benign and malignant prostatic disease about The objective of this application is to determine the mechanism(s) by which insulin-like growth factor (IGF) and epithelial growth factor (EGF) regulate the growth of human prostate epithelial cells, with emphasis on interactions between the IGF receptor, EGF receptor and the androgen receptor (AR) networks. The hypothesis to be tested is that androgen-induced genes also inducible by IGF or EGF provide an alternate mechanism for control of prostate epithelial cell proliferation and behavor. We will use a novel, well characterized family of SV40TAg immortalized human prostate epithelial cells, both androgen receptor negative (M12AR-) and androgen receptor positive (M12AR+) to achieve these specific aims: (1) To identify key genes induced in common in androgen receptor positive Ml2 cells by both androgen (DHT) and IGF or EGF by applying cDNA microarray analysis; (2) To determine the mechanism(s) by which IGF and EGF regulate prostate cell growth in vitro and in vivo. Candidate genes will be either over expressed or reduced in expression in the appropriate cell line by transfection or introduction of morpholino antisense oligonucleotides or antisense constructs. Proliferation, apoptosis, and differentiation will be assessed in vitro and in vivo by orthotopic injection into athymic nude mice; (3) To determine the expression patterns of the IGF, EGF, and androgen regulated genes identified in Aim 1 among human benign and malignant prostatic tissues. Prostate tissue arrays will be prepared from 400 prostate cancers and screened by immunohistochemistry or in situ hybridization, to confirm expression and assess the frequency of expression of the genes evaluated in our experimental system. These studies will provide comprehensive and unique insights into the mechanisms by which peptide growth factors provide alternate pathways to control prostate epithelial cell proliferation in benign and malignant states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: REGULATION OF SLO SPLICING IN THE UROGENITAL SYSTEM Principal Investigator & Institution: Davies, Kevin P.; Urology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2004; Project Start 10-APR-2004; Project End 31-MAR-2007 Summary: (provided by applicant): Dr. Kevin Davies has several years of experience as a molecular biologist. He has recently entered a new field of study, Urology. This K01 application will allow him to gain experience in the basic concepts of urogenital

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physiology. He will then be in an ideal position to apply the techniques of molecular biology to fundamental problems in the filed of Urology as an independent researcher. The Dept. of Urology at Albert Einstein College of Medicine is an excellent environment to gain experience in urogenital physiology. It has an active multi-disciplinary research group, which includes leaders in the filed of Urology, such as Dr, Arnold Melman and Dr. George Christ. The Dept conducts both clinical and basic research, and is active in translating this work from the laboratory to clinical therapies. In order to gain experience in urogenital physiology this research project will investigate the effect of hormones on splicing of the Slo gene in urogenital smooth muscle tissue in vivo and in vitro. Our working hypothesis is that SIo isoform expression in smooth muscle myocytes is modulated by hormones, and moreover, that these changes in isoform expression are relevant to urogenital physiology/dysfunction. Specifically we will look at the effects of hormones (stress axis hormones and sex hormones on the splicing of the Slo gene in female rats in vivo. Changes in the splicing of the Slo gene will be monitored in the smooth muscle tissue of these animals (aorta, colon, bladder and vagina). The different splice forms of the Slo gene will be characterized for their cellular and physiological function. In addition, a reporter construct will be developed which will allow real time analysis of splicing in cultured rat smooth muscle cells (aorta, colon, bladder and vagina). The ability of hormones to effect splicing in this in vitro system will be analyzed, as well as investigations into the signaling pathways that determine Slo splicing. This research project will allow Dr. Davies to develop a thorough understanding of urogenital physiology, while at the same time allowing him to utilize his experience in molecular biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SAW PALMETTO USE AND RISK OF PROSTATE CANCER Principal Investigator & Institution: Lee, I-Min; Assistant Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Apart from non-melanoma skin cancer, prostate cancer is the most commonly diagnosed cancer among men in the United States today. In spite of its importance, few modifiable predictors of this disease have been established. Well-established risk factors for prostate cancer (e.g., age) are not amenable to modification and, hence, have limited utility as targets of primary prevention strategies. There is a need to identify other risk factors that can be controlled. 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone, has been proposed to play a key role in the etiology of prostate cancer; thus, the NCI is currently testing finasteride, a 5-alpha reductase inhibitor, in the prevention of prostate cancer in an ongoing, randomized clinical trial. No information is available on other agents capable of inhibiting 5-alpha reductase and prostate cancer risk in men. Saw palmetto, derived from the berry of the American palm tree, can inhibit 5-alpha reductase activity. Saw palmetto has been shown to be as effective as finasteride in the treatment of urinary symptoms from benign prostatic hyperplasia. No data are available regarding its association with prostate cancer incidence in men; however, in vitro studies show inhibition of growth of prostate cancer cell lines. Therefore, we propose to conduct a retrospective cohort study among 16,700 physicians (mean age 67 years) to test the hypothesis that saw palmetto use reduces the risk of developing prostate cancer. These men currently are being followed as part of two other funded studies, the Physicians' Health Study I and II. Information on the development of prostate cancer is being collected in these two studies, as is a whole host of other information on health habits

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Dihydrotestosterone

and medical history. In this application, we propose to retrospectively collect details on the use of saw palmetto (when started and stopped, dose, brand) by adding questions to the scheduled 72-month follow-up questionnaire in these two other studies. During the proposed period of study, we anticipate that 790 cases of prostate cancer will develop. Power calculations show adequate power to detect a 45% reduction in risk of prostate cancer associated with saw palmetto use. At little additional cost, the data from this study will contribute to the knowledge infrastructure regarding whether large scale, informative trials on saw palmetto use and prostate cancer risk should be supported in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SHORT CHAIN DEHYDROGENASES IN RETINOL/STEROL METABOLISM Principal Investigator & Institution: Kedishvili, Natalia Y.; Molecular Biology and Biochem; University of Missouri Kansas City Kansas City, Mo 64110 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Retinoid and steroid hormones regulate a variety of physiological processes from morphogenesis to reproduction. Biosynthesis of both types of hormones involves oxidation and reduction of their corresponding precursors to the biologically active forms. Recent data from this and other laboratories suggest that mammalian tissues contain a group of elated enzymes capable of utilizing in vitro both retinoid and steroid alcohols and aldehydes as substrates. These enzymes share more than 40 percent sequence identity and belong to the superfamily of short-chain dehydrogenases/reductases. The main hypotheses of this proposal are that: (1) this group of structurally related enzymes is involved in biosynthesis of both retinoid and steroid hormones in vivo; (2) individual retinol/sterol dehydrogenases exhibit different tissue-specific expression patterns in human tissues, which determines their contribution to each metabolic pathway; and (3) the active site of these microsomal dehydrogenases faces the cytosol, where the NAD+-dependent enzymes function in the oxidative direction, and the NADP+-dependent enzymes function in the reductive direction. The existence of common enzymes should provide the means for joint regulation of retinoid and steroid signaling pathways. This hypothesis is consistent with the observations that retinoic acid significantly decreases serum levels of dihydrotestosterone and that the levels of retinoic acid are decreased in prostate carcinoma tissue. The overall objective of this proposal is to determine the role of the human microsomal retinol/sterol dehydrogenases, recently identified by this laboratory, in retinoid and steroid metabolism in the cells. The specific aims of this proposal are to: (1) develop a procedure for preparation of catalytically active purified recombinant retinol/sterol dehydrogenases; (2) characterize the substrate specificity and catalytic properties of the human retinol/sterol dehydrogenases; (3) determine the expression patterns of retinol/sterol dehydrogenases in human tissues; and 4) determine the topology of transmembrane insertion of human dehydrogenases in the microsomal membrane. Accomplishment of these objectives will allow us to gain understanding of the role of this new group of short-chain dehydrogenases in retinoid and steroid metabolism in health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: SMALL ANIMAL PET IMAGING OF RECEPTOR BASED AGENTS Principal Investigator & Institution: Rowland, Douglas J.; Radiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130

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Timing: Fiscal Year 2002; Project Start 25-SEP-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE/FUNCTION DEHYDROGENASE

OF

3A-HYDROXYSTEROID

Principal Investigator & Institution: Penning, Trevor M.; Professor; Pharmacology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-MAY-1994; Project End 30-APR-2003 Summary: Hydroxysteroid dehydrogenases (HSDs) play pivotal roles in the biosynthesis and inactivation of all steroid hormones. In target tissues they regulate occupancy of nuclear receptors by interconverting potent steroid hormones with their cognate inactive metabolites. HSDs belong to two protein superfamilies the short-chain dehydrogenase/ reductases (SDRs) and the aldo-keto reductases (AKRs). Rat liver 3alpha-HSD is the most thoroughly characterized HSD that is an AKR. Crystal structures of the apoenzyme [E], its binary complex [E NADP+] and ternary complex with a competitive inhibitor [E NADP+ testosterone] are described. Structure-function studies on 3alpha-HSD will provide unique insight into catalysis and ligand recognition in all steroid metabolizing AKRs (e.g., 3alpha-, 17beta-, and 20alpha-HSDs, and delta 4-3 ketosteriod 5beta-reductase). X-ray crystal structures of recombinant rat liver 3alphaHSD (rr3alpha- HSD) containing either 5alpha-dihydrotestosterone (5alpha-DHT) or 5beta- DHT are now sought. In these structures the 3-ketosteroid substrate is either planar (A/B trans-ring fusion) or significantly bent (A/B cis- ring fusion) and will identify the catalytic acid. The structure of recombinant human type 2 3alpha-HSD NADP+ 4-androstene-3, 17-dione complex is also sought. This AKR has both 3alphaand 17beta-HSD activity, may regulate prostate androgen receptor occupancy, yet binds steroids backwards (D ring instead of A ring first) and upside down (alpha-face in the beta-face orientation). Using rr3alpha-HSD, stopped- flow fluorescence spectroscopy, primary deuterium (4R-NAD(P)D), and solvent (D20) kinetic isotope effects will determine whether movement of a nucleotide-clamping loop is rate-limiting in the kinetic mechanism, and whether hydride transfer or proton donation is rate-limiting in the chemical step. pH rate profiles using mutants of the catalytic tetrad (Y55, H117, K84 and D50) will reveal the identity of the general acid by titration. Residues involved in cofactor binding will be mutated to either invert the stereochemistry of hydride transfer or change preference from NADPH to NADH. Knowledge of the steroid pocket will be exploited to alter specificity: (1) 5beta-reductase activity will be introduced by mutating tetrad residues; (2) 20alpha-HSD activity will be engineered by either mutating residues in the steroid pocket or by constructing 3alpha/20alpha-HSD chimeras in which loop regions of the pocket are swapped; and (4) the C-terminal loop (a major determinant of 3alpha- 17beta- and 20alpha-HSD specificity) will be randomly mutagenized by phagedisplay. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TESTOSTERONE DIFFERENTIATION

EFFECTS

ON

PLURIPOTENT

CELL

Principal Investigator & Institution: Gonzalez-Cadavid, Nestor F.; Charles R. Drew University of Med & Sci 1731 East 120Th Street Los Angeles, Ca 900593025 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008

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Dihydrotestosterone

Summary: Testosterone (T) administration increases skeletal muscle mass in men, causing hypertrophy of type I and II fibers, and increasing myonuclei and satellite cells, while reducing fat mass. We propose that these effects are due in part to the modulation of the conversion of pluripotent cells (PPC) residing in the skeletal muscle into myogenic and adipogenic lineages. Our hypothesis is that androgens stimulate through an androgen receptor (AR) mechanism: 1) the in vitro conversion of embryonic mesodermal PPC into the myogenic lineage, while inhibiting their adipogenic potential, and these effects can be replicated in cultures of non-embryonic PPC from mouse muscle; and 2) the conversion of non-embryonic PPC into satellite-like cells, which would donate their nuclei into pre-existing fibers, both in vitro and in vivo. Our Aim 1 is to determine in vitro whether: a) T and DHT modulate embryonic non-muscle PPC differentiation into myogenic or adipogenic lineages through an AR-dependent mechanism; and b) these effects can be replicated in primary cultures of PPC from mouse muscle. For a) we will characterize in the mouse C3H/10T1/2 cell line, the effects of increasing doses of T and DHT, without or with an AR antagonist, on: i) myogenesis, utilizing early, intermediate, and late markers; and ii) adipogenesis, utilizing early and late markers. Measurements will be performed by quantitative immunocytochemistry, western blot, and RT/PCR. For b) we will perform similar determinations on PPC cultures from young mouse muscle: the regenerating muscle fibroblasts (RMF) and/or the side-population (SP) cells. Our Aim 2 is to determine whether: a) androgen stimulation of myogenic conversion of the muscle PPC in vitro generates satellite-like cells that donate their nuclei to myotubes in an AR-dependent process; and b) whether this occurs in vivo in PPC explants into mouse skeletal muscle. For a) we will label the nuclei of muscle PPC, and incubate PPC with mouse C2C12 myoblasts or myotubes, to determine whether androgens stimulate MyoD expression and the fusion of the donor nuclei into myotubes, in an AR-dependent pathway. For b), the labeled PPC will be implanted in vivo into regenerating muscle, in intact and castrated nude mice treated or not with T, applying the same end-points as in vitro. These studies would provide novel insights on the mechanisms of androgen action and have implications for potential therapeutic uses of androgens for aging-related sarcopenia and other conditions associated with loss of muscle mass and function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TESTOSTERONE:PHYSICAL HEMODIALYSIS

FUNCTION

IN

MEN

ON

Principal Investigator & Institution: Bhasin, Shalender; Professor and Chief; Internal Medicine; Charles R. Drew University of Med & Sci 1731 East 120Th Street Los Angeles, Ca 900593025 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 30-JUN-2005 Summary: Malnutrition and loss of muscle mass (sarcopenia) are common in patients with end stage renal disease on hemodialysis and associated with increased mortality, impaired physical function, disability, and poor quality of life. Therefore, therapeutic interventions that can increase muscle mass and strength might improve physical function, general health perceptions, and reduce disability. Testosterone, when given in physiologic replacement doses, is an attractive anabolic intervention because it has been proven relatively safe, and effective in increasing muscle mass and strength in healthy hypogonadal men, older men with low testosterone levels, and HIV- infected men with weight loss. The primary objective of this study is to determine if testosterone replacement of men on maintenance hemodialysis who have low testosterone levels will increase their fat-free mass, muscle strength, physical function, and health-related

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quality of life. A second objective is to elucidate the mechanisms by which testosterone increases muscle mass. Men with end stage renal disease, 18-75 yrs of age, with serum testosterone less than 300 ng/dL, who are on maintenance hemodialysis, and free of acute illness, will be randomly assigned to receive either two placebo or two testosterone transdermal patches daily for 16 weeks. Two testosterone patches will nominally delivery 10 mg testosterone daily, and raise serum testosterone levels into the mid-range for healthy young men. Energy and protein intake, hemodialysis regimen, and erythropeitin dose will be standardized. The following outcomes will be measured at baseline and after 16 weeks: body composition by DEXA scan, deuterium oxide and sodium bromide dilution; thigh muscle volume by MRI scan; muscle performance by measurements of 5-repetition maximum strength, power, and endurance in the leg press exercise; and effort independent muscle performance by force:EMG relationship; physical function by stair climbing power, getting up from a chair, and walking speed; self-reported disability and kidney disease quality of life by validated instruments; fractional synthesis rates of mixed skeletal muscle protein and myosin heavy chain during a primed, continuous infusion of L-[1,213C]-leucine. Total and free testosterone and dihydrotestosterone levels will be measured as markers of androgen bioavailability, and LH, FSH, and SHBG as markers of androgen action. For safety, we will follow hemoglobin/hematocrit, AST and ALT, PSA, plasma lipids, apolipoproteins, and lipoprotein particles, and insulin sensitivity by the modified Bergman Minimal Model. Muscle biopsies will also be used for measurements of myostatin, IGF-1, and IGFBP-4 mRNA and protein concentrations by RT-PCR and Western blot analyses. A multi-disciplinary team of investigators, careful subject selection, access to a large patient pool, attention to potential confounding variables such as dialysis intensity, erythropoeitin dose, dietary intake and exercise stimulus, and power and effect size, and state-of-the-art methods should maximize the chances of detecting treatment effects and elucidating the mechanism of androgen action. Therefore, if successful, this study should help identify a therapeutic intervention that might improve physical function and reduce disability in men with end stage renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRIAL OF DHT GEL FOR HRT IN ELDERLY HYPOGONAL MEN Principal Investigator & Institution: Dobs, Adrian S.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: Male hypogonadism has been associated with signs and symptoms of sexual dysfunction, decreased body hair, and osteoporosis. At present, there are several androgen preparations available in the United States. These include injectable testosterone esters, two oral preparations, fluoxymesterone and methyl-testosterone, and two types of transdermal androgen patches presently available. However, each has its own disadvantages for testosterone supplementation. The most significant disadvantage involves the prostate. Testosterone can increase the prostate size leading to benign prostate hypertrophy (BPH), especially in older men. In looking for an improved androgen delivery system as well as an androgen that would be safer for elderly men, a testosterone derivative, dihydrotestosterone (DHT) 1% hydroalcholic gel (DHT-gel) has been developed to allow transdermal application over broad areas of skin in measured fashion without visible identifying patches. This method uses natural testosterone products and allows a measured dose to be dispensed, which then can be rubbed, on to a given area of skin by the user. The gel liquefies and the alcohol rapidly evaporate leaving an unrecognizable film of testosterone on the skin which is then

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Dihydrotestosterone

rapidly incorporated into the epidermal tissue. There is no sticky residue. Results from the phase I testing of DHT-gel indicate that the daily application of 64 grams of gel (100 mg T) to the upper arm/shoulder and trunk region yields stable DHT levels. No evidence of skin irritation was found in patients with T-gel in the phase I study. This study showed some very promising data that the size of prostate did not increase and some decrease in size. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UBIQUITINATION AND DEGRADATION IN CANCER THERAPY Principal Investigator & Institution: Sakamoto, Kathleen M.; Pediatrics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2004; Project Start 06-JUL-2004; Project End 30-JUN-2006 Summary: (provided by applicant): Prostate cancer is the most common type of cancer diagnosed in men and the second most common cause of death from cancer. Initial therapy for patients with androgen-dependent prostate cancer includes hormonal therapy to inhibit the biological effects of androgen receptor (AR) signaling. Recent evidence suggests that the AR is critical for tumor growth in androgen-refractory prostate cancer cells. The ubiquitin proteasome pathway is the primary pathway for protein turnover in all eukaryotic cells that involves the assembly of an ubiquitin chain on a substrate, which then targets the multi-ubiquitinated protein for degradation by the 26S proteasome. A protein complex known as, the SCF (S_kp1, Cullin, F-box, and Hrtl/Rbx) ubiquitin ligase specifically targets proteins for ubiquitination and subsequent degradation. We previously demonstrated that a bridging molecule or Protac (Proteolysis Targeting Chimeric molecule) promotes in vitro ubiquitination of a stable protein, Methionine Aminopeptidase-2, and an unstable protein, the estrogen receptor, by SCF(-TRCP. We have synthesized a Protac (Protac-3) consisting of the ligand of AR, dihydroxytestosterone (DHT), and the I(B(-phosphopeptide, which binds SCF(-TRCP. Our goal is to develop a new technology in which a Protac links the AR to SCF(-TRCP, resulting in ubiquitination and degradation of AR. The specific aims of this proposal are to: 1) Test the hypothesis that a phosphopeptide-DHT chimera (Protac-3) will link AR to SCF(-TRCP, and direct the ubiquitination and degradation of AR in vitro; 2) Test the hypothesis that a phosphopeptide-DHT chimera (Protac-3) will link AR to SCF(-TRCP, and increase the ubiquitination and degradation of AR in cells; and 3) Test the hypothesis that small non-peptidic ligands that bind a-TRCP can be used to generate testosterone-based Protacs that increase AR ubiquitination and degradation. We hypothesize that AR can be targeted to SCF(-TRCP resulting in increased turnover of AR in prostate cancer cells. Development of this technology will lead to novel approaches to treat androgen dependent and -independent disease in hopes of improving the survival of men with prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National

3

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

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Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “dihydrotestosterone” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for dihydrotestosterone in the PubMed Central database: •

Alteration in the metabolism of dihydrotestosterone in elderly men with prostate hyperplasia. by Morimoto I, Edmiston A, Horton R.; 1980 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371692

•

Antiestrogenic action of dihydrotestosterone in mouse breast. Competition with estradiol for binding to the estrogen receptor. by Casey RW, Wilson JD.; 1984 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=425420

•

Circulating dihydrotestosterone may not reflect peripheral formation. by Toscano V, Horton R.; 1987 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=424493

•

Concentration of Dihydrotestosterone and 3[alpha]-Androstanediol in Naturally Occurring and Androgen- Induced Prostatic Hyperplasia in the Dog. by Moore RJ, Gazak JM, Quebbeman JF, Wilson JD.; 1979 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372209

•

Dihydrotestosterone in Prostatic Hypertrophy. I. THE FORMATION AND CONTENT OF DIHYDROTESTOSTERONE IN THE HYPERTROPHIC PROSTATE OF MAN. by Siiteri PK, Wilson JD.; 1970 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322657

•

Dihydrotestosterone in Prostatic Hypertrophy. II. THE FORMATION AND CONTENT OF DIHYDROTESTOSTERONE IN THE HYPERTROPHIC CANINE PROSTATE AND THE EFFECT OF DIHYDROTESTOSTERONE ON PROSTATE GROWTH IN THE DOG. by Gloyna RE, Siiteri PK, Wilson JD.; 1970 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322658

•

Feed-forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5 alpha-reductase. by George FW, Russell DW, Wilson JD.; 1991 Sep 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52442

4

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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•

High efficiency covalent radiolabeling of the human androgen receptor. Studies in cultured fibroblasts using dihydrotestosterone 17 beta-bromoacetate. by Kovacs WJ, Turney MK.; 1988 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329576

•

Metabolic Clearance Rate and Blood Production Rate of Testosterone and Dihydrotestosterone in Normal Subjects, during Pregnancy, and in Hyperthyroidism. by Saez JM, Forest MG, Morera AM, Bertrand J.; 1972 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292254

•

Regulation of cytoplasmic dihydrotestosterone binding in dog prostate by 17 betaestradiol. by Moore RJ, Gazak JM, Wilson JD.; 1979 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371961

•

The Metabolic Clearance Rate and Origin of Plasma Dihydrotestosterone in Man and Its Conversion to the 5[alpha]-Androstanediols. by Mahoudeau JA, Bardin CW, Lipsett MB.; 1971 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292065

•

The Source of Plasma Dihydrotestosterone in Man. by Ito T, Horton R.; 1971 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=442061

•

Tissue content of dihydrotestosterone in human prostatic hyperplasis is not supranormal. by Walsh PC, Hutchins GM, Ewing LL.; 1983 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370466

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with dihydrotestosterone, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “dihydrotestosterone” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for dihydrotestosterone (hyperlinks lead to article summaries):

6

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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•

A comparison of the effects of neonatally administered testosterone, testosterone propionate and dihydrotestosterone on aggressive and sexual behaviour in the female golden hamster. Author(s): Payne AP. Source: The Journal of Endocrinology. 1976 April; 69(1): 23-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=944751

•

A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. Author(s): Ly LP, Jimenez M, Zhuang TN, Celermajer DS, Conway AJ, Handelsman DJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 September; 86(9): 4078-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549629

•

A model for the turnover of dihydrotestosterone in the presence of the irreversible 5 alpha-reductase inhibitors GI198745 and finasteride. Author(s): Gisleskog PO, Hermann D, Hammarlund-Udenaes M, Karlsson MO. Source: Clinical Pharmacology and Therapeutics. 1998 December; 64(6): 636-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9871428

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A paper chromatographic saturation analysis method for measuring estradiol, testosterone and 5alpha-dihydrotestosterone from the same sample. Author(s): Carstensen H, Backstrom T. Source: J Steroid Biochem. 1976 February; 7(2): 145-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1263503

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A rapid method for the determination of 5 alpha-dihydrotestosterone in Thai males receiving medroxyprogesterone acetate. Author(s): Werawatgoompa S, Dusitsin N, Sooksamiti P, Leepipatpaiboon S, Virutamasen P, Boonsiri B. Source: Contraception. 1982 May; 25(5): 523-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6213376

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A review of the formation and binding of 5 alpha-dihydrotestosterone in the mechanism of action of androgens in the prostate of the rat and other species. Author(s): Mainwaring WI. Source: Journal of Reproduction and Fertility. 1975 August; 44(2): 377-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=169350

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A simple radioimmunoassay for plasma testosterone plus 5alphadihydrotestosterone. Author(s): Wang C, Youatt G, O'Connor S, Dulmanis A, Hudson B. Source: J Steroid Biochem. 1974 October; 5(6): 551-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4427451

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A specific and rapid determination of human skin dihydrotestosterone cytosol receptor. Author(s): Evain D, Savage NO, Binet E. Source: The Journal of Clinical Endocrinology and Metabolism. 1977 August; 45(2): 3636. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=885998

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Abnormality of intracellular 5 alpha-dihydrotestosterone binding in simple hypospadias: studies on equilibrium steroid binding in sonicates of genital skin fibroblasts. Author(s): Keenan BS, McNeel RL, Gonzales ET. Source: Pediatric Research. 1984 February; 18(2): 216-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6701049

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Absorption of dihydrotestosterone (DHT) after its intramuscular administration. Author(s): Diaz-Sanchez V, Larrea F, Ulloa-Aguirre A, Garza-Flores J, Richards E, Veayra F. Source: Fertility and Sterility. 1989 March; 51(3): 493-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2920848

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Acute effects of testicular and adrenal cortical blockade on protein synthesis and dihydrotestosterone content of human prostate tissue. Author(s): Liu J, Geller J, Albert J, Kirshner M. Source: The Journal of Clinical Endocrinology and Metabolism. 1985 July; 61(1): 129-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2581988

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Administration of dihydrotestosterone to rhesus monkeys inhibits gonadotropinstimulated ovarian steroidogenesis. Author(s): Zeleznik AJ, Little-Ihrig L, Ramasawamy S. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 February; 89(2): 860-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14764806

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Age related changes in free plasma testosterone, dihydrotestosterone and oestradiol. Author(s): Pirke KM, Doerr P. Source: Acta Endocrinol (Copenh). 1975 September; 80(1): 171-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1173981

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Age-dependent change of serum 5alpha-dihydrotestosterone and its relation to testosterone in man. Author(s): Nawata H, Kato K, Ibayashi H. Source: Endocrinol Jpn. 1977 February; 24(1): 41-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=862570

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Age-related secretion of androstenedione, testosterone and dihydrotestosterone by the human testis. Author(s): Giusti G, Gonnelli P, Borrelli D, Fiorelli G, Forti G, Pazzagli M, Serio M. Source: Experimental Gerontology. 1975; 10(5): 241-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1204687

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Albumin possesses intrinsic enolase activity towards dihydrotestosterone which can differentiate benign from malignant breast tumors. Author(s): Drmanovic Z, Voyatzi S, Kouretas D, Sahpazidou D, Papageorgiou A, Antonoglou O. Source: Anticancer Res. 1999 September-October; 19(5B): 4113-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10628362

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Alteration in the metabolism of dihydrotestosterone in elderly men with prostate hyperplasia. Author(s): Morimoto I, Edmiston A, Horton R. Source: The Journal of Clinical Investigation. 1980 September; 66(3): 612-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6156957

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Androgen administration in middle-aged and ageing men: effects of oral testosterone undecanoate on dihydrotestosterone, oestradiol and prostate volume. Author(s): Pechersky AV, Mazurov VI, Semiglazov VF, Karpischenko AI, Mikhailichenko VV, Udintsev AV. Source: International Journal of Andrology. 2002 April; 25(2): 119-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903662

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Androgen receptor-mediated stimulation of 17 beta-hydroxysteroid dehydrogenase activity by dihydrotestosterone and medroxyprogesterone acetate in ZR-75-1 human breast cancer cells. Author(s): Couture P, Theriault C, Simard J, Labrie F. Source: Endocrinology. 1993 January; 132(1): 179-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8380373

52

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Androgen-induced prostate-specific antigen gene expression is mediated via dihydrotestosterone in LNCaP cells. Author(s): Zhu YS, Cai LQ, You X, Cordero JJ, Huang Y, Imperato-McGinley J. Source: Journal of Andrology. 2003 September-October; 24(5): 681-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954658

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Androgens in the feedback regulation of gonadotropin secretion in men: effects of administration of dihydrotestosterone to eugonadal and agonadal subjects and of spironolactone to eugonadal subjects. Author(s): Gooren LJ, van der Veen EA, van Kessel H, Harmsen-Louman W, Wiegel AR. Source: Andrologia. 1984 July-August; 16(4): 289-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6433746

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Androgen-stimulated pubertal growth: the effects of testosterone and dihydrotestosterone on growth hormone and insulin-like growth factor-I in the treatment of short stature and delayed puberty. Author(s): Keenan BS, Richards GE, Ponder SW, Dallas JS, Nagamani M, Smith ER. Source: The Journal of Clinical Endocrinology and Metabolism. 1993 April; 76(4): 9961001. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8473416

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Androstanediol and 5-androstenediol profiling for detecting exogenously administered dihydrotestosterone, epitestosterone, and dehydroepiandrosterone: potential use in gas chromatography isotope ratio mass spectrometry. Author(s): Shackleton CH, Roitman E, Phillips A, Chang T. Source: Steroids. 1997 October; 62(10): 665-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9381514

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Androstanediol glucuronide isomers in normal men and women and in men infused with labeled dihydrotestosterone. Author(s): Rittmaster RS, Thompson DL, Listwak S, Loriaux DL. Source: The Journal of Clinical Endocrinology and Metabolism. 1988 January; 66(1): 2126. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3335605

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Androstenedione is an important precursor of dihydrotestosterone in the genital skin of women and is metabolized via 5 alpha-androstanedione. Author(s): Stanczyk FZ, Matteri RK, Kaufman FR, Gentzschein E, Lobo RA. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1990 September; 37(1): 129-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2242346

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Androstenedione may be a more important precursor of tissue dihydrotestosterone than testosterone in women. Author(s): Silva PD, Gentzschein EE, Lobo RA. Source: Fertility and Sterility. 1987 September; 48(3): 419-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3622795

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Antiserum to 5alpha-dihydrotestosterone: production, characterization and use in radioimmunoassay. Author(s): Bauminger S, Kohen F, Lindner HR, Weinstein A. Source: Steroids. 1974 October; 24(4): 477-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4473080

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Application of a non-chromatographic radio-immunoassay to the measurement of plasma 5 alpha-dihydrotestosterone in females with idiopathic hirsutism. Author(s): Montalto J, Yong AB, Funder JW, Connelly JF. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1989 May; 49(3): 303-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2740825

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Association of testosterone and dihydrotestosterone with externalizing behavior in adolescent boys and girls. Author(s): Maras A, Laucht M, Gerdes D, Wilhelm C, Lewicka S, Haack D, Malisova L, Schmidt MH. Source: Psychoneuroendocrinology. 2003 October; 28(7): 932-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12892659

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Autoradiographic localization of tritium-labeled dihydrotestosterone in human vas deferens. Author(s): Beckman WC Jr, Fried FA, Stafford SJ, Mickey DD. Source: Journal of Andrology. 1986 May-June; 7(3): 197-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3722002

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Bcl-2 antagonizes the combined apoptotic effect of transforming growth factor-beta and dihydrotestosterone in prostate cancer cells. Author(s): Bruckheimer EM, Kyprianou N. Source: The Prostate. 2002 October 1; 53(2): 133-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12242728

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Behavioral characteristics of beef steers administered estradiol, testosterone and dihydrotestosterone. Author(s): Dykeman DA, Katz LS, Foote RH. Source: Journal of Animal Science. 1982 December; 55(6): 1303-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6891699

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Benign prostatic hyperplasia: dihydrotestosterone and 5 alpha-reductase inhibition therapy. Author(s): Imperato-McGinley J. Source: Prog Clin Biol Res. 1994; 386: 197-203. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7528387

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Binding analysis of 1alpha- and 17alpha-dihydrotestosterone derivatives to homodimeric sex hormone-binding globulin. Author(s): Metzger J, Schnitzbauer A, Meyer M, Soder M, Cuilleron CY, Hauptmann H, Huber E, Luppa PB. Source: Biochemistry. 2003 November 25; 42(46): 13735-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622020

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Binding of dihydrotestosterone, R 1881 and R 5020 in cytosols from normal, benign hypertrophic and cancerous human prostates. Author(s): Nozumi K, Sato R, Ito H, Maruoka M, Shimazaki J. Source: Urologia Internationalis. 1981; 36(2): 79-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6169181

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Biochemical markers in colon tumorigenesis: retinoic acid and dihydrotestosteronebinding proteins. Author(s): Sani BP, Banerjee CK, Brockman RW. Source: Cancer Detection and Prevention. 1981; 4(1-4): 223-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6299560

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Biological effects of androgens and identification of specific dihydrotestosteronebinding sites in cultured human fetal epiphyseal chondrocytes. Author(s): Carrascosa A, Audi L, Ferrandez MA, Ballabriga A. Source: The Journal of Clinical Endocrinology and Metabolism. 1990 January; 70(1): 13440. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2294127

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Blood production rate of dihydrotestosterone in the syndrome of male pseudohermaphroditism with testicular feminization. Author(s): Tremblay RR, Kowarski A, Park IJ, Migeon CJ. Source: The Journal of Clinical Endocrinology and Metabolism. 1972 July; 35(1): 101-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5032507

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Carrier detection in the testicular feminisation syndrome: deficient 5 alphadihydrotestosterone binding in cultured skin fibroblasts from the mothers of patients with complete androgen insensitivity. Author(s): Hodgins MB, Duke EM, Ring D. Source: Journal of Medical Genetics. 1984 June; 21(3): 178-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6748013

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Changes in gonadotropins (LH, FSH), prolactin, androgens (testosterone, dihydrotestosterone) and estrogens (estradiol and estrone) during male pubescence. Author(s): Villalpando S, Mondragon L, Arreola F, Perez-Pasten E, Castaneda G, Alonso R, Cortes-Gallegos V. Source: Arch Invest Med (Mex). 1983 October-December; 14(4): 343-9. English, Spanish. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6678556

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Changes in the metabolism of dihydrotestosterone in the hyperplastic human prostate. Author(s): Isaacs JT, Brendler CB, Walsh PC. Source: The Journal of Clinical Endocrinology and Metabolism. 1983 January; 56(1): 13946. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6183287

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Characteristics of the cytoplasmic and nuclear dihydrotestosterone receptors of human thymic tissue. Author(s): Grossman CJ, Sholiton LJ, Helmsworth JA. Source: Steroids. 1983 July; 42(1): 11-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6673176

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Characterization of a cloned human dihydrotestosterone/androstanediol UDPglucuronosyltransferase and its comparison to other steroid isoforms. Author(s): Chen F, Ritter JK, Wang MG, McBride OW, Lubet RA, Owens IS. Source: Biochemistry. 1993 October 12; 32(40): 10648-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8399210

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Circadian rhythms in plasma levels of cortisol, dehydroepiandrosterone, delta 4androstenedione, testosterone and dihydrotestosterone of healthy young men. Author(s): Guignard MM, Pesquies PC, Serrurier BD, Merino DB, Reinberg AE. Source: Acta Endocrinol (Copenh). 1980 August; 94(4): 536-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6449126

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Circulating dihydrotestosterone may not reflect peripheral formation. Author(s): Toscano V, Horton R. Source: The Journal of Clinical Investigation. 1987 June; 79(6): 1653-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3584464

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Clinical application of dihydrotestosterone (DHT) binding assay of cultured skin fibroblasts for the prospective differential diagnosis of testicular feminization syndrome (TFS). Author(s): Wakimoto H, Takayasu S, Kurachi H, Komura H, Miyake A, Aono T, Tanizawa O, Matsumoto K. Source: Asia Oceania J Obstet Gynaecol. 1985 September; 11(3): 411-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4084108

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Clinical relevance of testosterone and dihydrotestosterone metabolism in women. Author(s): Rittmaster RS. Source: The American Journal of Medicine. 1995 January 16; 98(1A): 17S-21S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7825635

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Cognitive changes associated with supplementation of testosterone or dihydrotestosterone in mildly hypogonadal men: a preliminary report. Author(s): Cherrier MM, Craft S, Matsumoto AH. Source: Journal of Andrology. 2003 July-August; 24(4): 568-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826696

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Combination of subcutaneous levonorgestrel implants and transdermal dihydrotestosterone gel for male hormonal contraception. Author(s): Pollanen P, Nikkanen V, Huhtaniemi I. Source: International Journal of Andrology. 2001 December; 24(6): 369-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11737418

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Comparative pharmacokinetics of three doses of percutaneous dihydrotestosterone gel in healthy elderly men--a clinical research center study. Author(s): Wang C, Iranmanesh A, Berman N, McDonald V, Steiner B, Ziel F, Faulkner SM, Dudley RE, Veldhuis JD, Swerdloff RS. Source: The Journal of Clinical Endocrinology and Metabolism. 1998 August; 83(8): 2749-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9709942

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Comparison of dihydrotestosterone levels in prostatic cancer metastases and primary prostate cancer. Author(s): Geller J, Candari CD. Source: The Prostate. 1989; 15(2): 171-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2798234

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Comparison of methyltrienolone and dihydrotestosterone binding and metabolism in human genital skin fibroblasts. Author(s): Brown TR, Rothwell SW, Migeon CJ. Source: J Steroid Biochem. 1981 October; 14(10): 1013-22. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6975397

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Comparison of prostatic cancer tissue dihydrotestosterone levels at the time of relapse following orchiectomy or estrogen therapy. Author(s): Geller J, Albert JD, Nachtsheim DA, Loza D. Source: The Journal of Urology. 1984 October; 132(4): 693-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6471215

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Comparison of testosterone, 5alpha-dihydrotestosterone and 5alpha-adrostane-3beta, 17beta-diol metabolisms in human normal and hyperplastic prostates. Author(s): Morfin RF, Di Stefano S, Bercovici JP, Floch HH. Source: J Steroid Biochem. 1978 March; 9(3): 245-52. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=77360

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Comparison of testosterone, dihydrotestosterone, luteinizing hormone, and folliclestimulating hormone in serum after injection of testosterone enanthate of testosterone cypionate. Author(s): Schulte-Beerbuhl M, Nieschlag E. Source: Fertility and Sterility. 1980 February; 33(2): 201-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7353699

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Competitive inhibition by danazol of progesterone and dihydrotestosterone binding to human uterine progestin and androgen receptors. Author(s): Punnonen R, Lukola A. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1982 March; 14(3): 167-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7068110

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Complete androgen insensitivity with a normal amount of 5 alphadihydrotestosterone-binding activity in labium majus skin fibroblasts. Author(s): Kaufman M, Pinsky L, Baird PA, McGillivray BC. Source: American Journal of Medical Genetics. 1979; 4(4): 401-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=575468

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Concentrations of unconjugated 5 alpha-androstane-3 alpha, 17 beta-diol and 5 alphaandrostane-3 beta, 17 beta-diol and their precursor in human testicular tissue. Comparison with testosterone, 5 alpha-dihydrotestosterone, estradiol-17 beta, and with steroid concentrations in human epididymis. Author(s): Tamm J, Volkwein U, Kurniawan E, Becker H. Source: J Steroid Biochem. 1987 March; 26(3): 345-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3586650

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Contribution of dihydrotestosterone to male sexual behaviour. Author(s): Mantzoros CS, Georgiadis EI, Trichopoulos D. Source: Bmj (Clinical Research Ed.). 1995 May 20; 310(6990): 1289-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7773040

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Control of human sebocyte proliferation in vitro by testosterone and 5-alphadihydrotestosterone is dependent on the localization of the sebaceous glands. Author(s): Akamatsu H, Zouboulis CC, Orfanos CE. Source: The Journal of Investigative Dermatology. 1992 October; 99(4): 509-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1402009

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Conversion of 3H-testosterone to dihydrotestosterone in human hypertrophic prostatic tissue. Author(s): Baranowska B, Zgliczynski S. Source: Nuklearmedizin. 1979; 18(6): 297-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=94161

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Conversion of 5-androstene-3 beta, 17 beta-diol into testosterone and 5 alphadihydrotestosterone in androgen-sensitive organs of the rat and in human skin. Author(s): Hodgins MB, Hay JB. Source: Biochemical Society Transactions. 1974; 2(4): 596-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4448283

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Conversion of dihydrotestosterone to androstanediol glucuronide by female sexual skin. Author(s): Pasupuleti V, Lobo R, Horton R. Source: Steroids. 1988 March-April; 51(3-4): 269-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3217954

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Coregulatory effects of epidermal growth factor, dihydrotestosterone, and prolactin on benign human prostatic hyperplasia tissue culture proliferation. Author(s): Janssen T, Petein M, van Velthoven R, De Decker R, Assenmacher C, Corbusier A, Pasteels JL, Kiss R, Schulman C. Source: The Prostate. 1997 January 1; 30(1): 47-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9018335

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Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone. Author(s): Sack JS, Kish KF, Wang C, Attar RM, Kiefer SE, An Y, Wu GY, Scheffler JE, Salvati ME, Krystek SR Jr, Weinmann R, Einspahr HM. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 April 24; 98(9): 4904-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11320241

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Cytoplasmic receptors for 17 beta-estradiol, 5 alpha-dihydrotestosterone and progesterone in normal and abnormal human uterine tissues. Author(s): Grilli S, Ferreri AM, Gola G, Rocchetta R, Orlandi C, Prodi G. Source: Cancer Letters. 1977 March; 2(4-5): 247-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=45727

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Decreased plasma dehydroepiandrosterone sulfate and dihydrotestosterone concentrations in young men after myocardial infarction. Author(s): Slowinska-Srzednicka J, Zgliczynski S, Ciswicka-Sznajderman M, Srzednicki M, Soszynski P, Biernacka M, Woroszylska M, Ruzyllo W, Sadowski Z. Source: Atherosclerosis. 1989 October; 79(2-3): 197-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2532016

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Dehydroepiandrosterone and dihydrotestosterone recognition by human estrogenic 17beta-hydroxysteroid dehydrogenase. C-18/c-19 steroid discrimination and enzymeinduced strain. Author(s): Han Q, Campbell RL, Gangloff A, Huang YW, Lin SX. Source: The Journal of Biological Chemistry. 2000 January 14; 275(2): 1105-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10625652

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Destabilization of tumor necrosis factor-alpha mRNA by 5-alpha dihydrotestosterone in Jurkat cells. Author(s): Takei S, Redford A, Katayama S, Toyoda H. Source: Life Sciences. 2000 April 7; 66(20): Pl277-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10821125

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Dihydrotestosterone (DHT) modulates the ability of NSAIDs to induce apoptosis of prostate cancer cells. Author(s): Andrews P, Krygier S, Djakiew D. Source: Cancer Chemotherapy and Pharmacology. 2002 March; 49(3): 179-86. Epub 2002 January 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11935209

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Dihydrotestosterone accumulation in genital skin fibroblasts derived from elderly men with prostatic hyperplasia. Author(s): Morimoto I, Eto S, Inoue S, Izumi M, Hara T, Saito Y, Nagataki S. Source: The Journal of Clinical Endocrinology and Metabolism. 1992 August; 75(2): 6325. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1379259

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Dihydrotestosterone and testosterone levels in men screened for prostate cancer: a study of a randomized population. Author(s): Gustafsson O, Norming U, Gustafsson S, Eneroth P, Astrom G, Nyman CR. Source: British Journal of Urology. 1996 March; 77(3): 433-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8814852

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Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia. Author(s): Bartsch G, Rittmaster RS, Klocker H. Source: World Journal of Urology. 2002 April; 19(6): 413-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022710

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Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia. Author(s): Bartsch G, Rittmaster RS, Klocker H. Source: European Urology. 2000 April; 37(4): 367-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10765065

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Dihydrotestosterone as a selective cellular/nuclear localization vector for anti-gene peptide nucleic acid in prostatic carcinoma cells. Author(s): Boffa LC, Scarfi S, Mariani MR, Damonte G, Allfrey VG, Benatti U, Morris PL. Source: Cancer Research. 2000 April 15; 60(8): 2258-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10786693

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Dihydrotestosterone enhances transforming growth factor-beta-induced apoptosis in hormone-sensitive prostate cancer cells. Author(s): Bruckheimer EM, Kyprianou N. Source: Endocrinology. 2001 June; 142(6): 2419-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11356690

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Dihydrotestosterone formation in cultured human fibroblasts. Comparison of cells from normal subjects and patients with familial incomplete male pseudohermaphroditism, Type 2. Author(s): Wilson JD. Source: The Journal of Biological Chemistry. 1975 May 10; 250(9): 3498-504. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1123350

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Dihydrotestosterone heptanoate: synthesis, pharmacokinetics, and effects on hypothalamic-pituitary-testicular function. Author(s): Keenan BS, Eberle AJ, Sparrow JT, Greger NG, Panko WB. Source: The Journal of Clinical Endocrinology and Metabolism. 1987 March; 64(3): 55762. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3546348

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Dihydrotestosterone inhibits fetal rabbit pulmonary surfactant production. Author(s): Nielsen HC, Zinman HM, Torday JS. Source: The Journal of Clinical Investigation. 1982 March; 69(3): 611-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6916770

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Dihydrotestosterone is a peripheral paracrine hormone. Author(s): Horton R. Source: Journal of Andrology. 1992 January-February; 13(1): 23-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1551803

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Dihydrotestosterone levels at midpregnancy and term: a comparison with testosterone concentrations. Author(s): Abramovich DR, Herriot R, Stott J. Source: British Journal of Obstetrics and Gynaecology. 1983 March; 90(3): 232-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6830731

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Dihydrotestosterone measured in core biopsies from prostatic tissues. Author(s): Bruun E, Frandsen H, Nielsen K, Rasmussen LB, Vinnergaard T, FrimodtMoller C. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 1988; 11 Suppl 2: S27-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2468272

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Dihydrotestosterone metabolism. Author(s): Toscano V. Source: Clin Endocrinol Metab. 1986 May; 15(2): 279-92. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3521956

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Dihydrotestosterone promotes fighting behavior of female mice. Author(s): Schechter D, Howard SM, Gandelman R. Source: Hormones and Behavior. 1981 September; 15(3): 233-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7197661

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Dihydrotestosterone promotes vascular cell adhesion molecule-1 expression in male human endothelial cells via a nuclear factor-kappaB-dependent pathway. Author(s): Death AK, McGrath KC, Sader MA, Nakhla S, Jessup W, Handelsman DJ, Celermajer DS. Source: Endocrinology. 2004 April; 145(4): 1889-97. Epub 2003 December 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684616

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Dihydrotestosterone receptors in the human prostate. I. Nuclear concentration in normal, benign, and malignant tissues. Author(s): Lehoux JG, Benard B, Elhilali M. Source: Archives of Andrology. 1980 November; 5(3): 237-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6159829

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Dihydrotestosterone receptors in the human prostate: characterization by chromatography, electrophoresis, and isoelectric focusing. Author(s): Lehoux JG, Benard B, Elhilali M. Source: Archives of Andrology. 1985; 15(1): 33-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4096573

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Dihydrotestosterone regulates plasma sex-hormone-binding globulin in prepubertal males. Author(s): el-Awady MK, Salam MA, Gad YZ, el-Saban J. Source: Clinical Endocrinology. 1989 March; 30(3): 279-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2591057

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Dihydrotestosterone regulation of semen in male pseudohermaphrodites with 5 alpha-reductase-2 deficiency. Author(s): Cai LQ, Fratianni CM, Gautier T, Imperato-McGinley J. Source: The Journal of Clinical Endocrinology and Metabolism. 1994 August; 79(2): 40914. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8045956

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Dihydrotestosterone stimulates 5 alpha-reductase activity in pubic skin fibroblasts. Author(s): Mowszowicz I, Melanitou E, Kirchhoffer MO, Mauvais-Jarvis P. Source: The Journal of Clinical Endocrinology and Metabolism. 1983 February; 56(2): 320-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6218182

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Dihydrotestosterone treatment in adolescents with delayed puberty: does it explain insulin resistance of puberty? Author(s): Saad RJ, Keenan BS, Danadian K, Lewy VD, Arslanian SA. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 October; 86(10): 4881-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11600557

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Dihydrotestosterone, stanozolol, androstenedione and dehydroepiandrosterone sulphate inhibit leptin secretion in female but not in male samples of omental adipose tissue in vitro: lack of effect of testosterone. Author(s): Pineiro V, Casabiell X, Peino R, Lage M, Camina JP, Menendez C, Baltar J, Dieguez C, Casanueva F. Source: The Journal of Endocrinology. 1999 March; 160(3): 425-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10076188

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Dihydrotestosterone: a rationale for its use as a non-aromatizable androgen replacement therapeutic agent. Author(s): Swerdloff RS, Wang C. Source: Baillieres Clin Endocrinol Metab. 1998 October; 12(3): 501-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10332569

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Direct conversion of testosterone to dihydrotestosterone glucuronide in man. Author(s): Ishimaru T, Edmiston A, Pages L, Horton R. Source: The Journal of Clinical Endocrinology and Metabolism. 1978 December; 47(6): 1282-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=263350

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Discovery of the role of dihydrotestosterone in androgen action. Author(s): Bruchovsky N, Wilson JD. Source: Steroids. 1999 November; 64(11): 753-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10577831

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Dissociation of the 5 alpha-reductase activity from the specific dihydrotestosterone binding activity in cultured human fibroblasts. Author(s): Ozasa H, Tominaga T, Nishimura T, Takeda T. Source: Endokrinologie. 1981 October; 78(1): 115-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7318772

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Early and late long-term effects of vasectomy on serum testosterone, dihydrotestosterone, luteinizing hormone and follicle-stimulating hormone levels. Author(s): Mo ZN, Huang X, Zhang SC, Yang JR. Source: The Journal of Urology. 1995 December; 154(6): 2065-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7500459

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Effect of 5-alpha dihydrotestosterone on T-cell proliferation of the female nonobese diabetic mouse. Author(s): Toyoda H, Takei S, Formby B. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1996 December; 213(3): 287-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8985314

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Effect of aging on endogenous level of 5 alpha-dihydrotestosterone, testosterone, estradiol, and estrone in epithelium and stroma of normal and hyperplastic human prostate. Author(s): Krieg M, Nass R, Tunn S. Source: The Journal of Clinical Endocrinology and Metabolism. 1993 August; 77(2): 37581. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7688377

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Effect of castration and subsequent substitution with testosterone, dihydrotestosterone and oestradiol on sexual preference behaviour in the male rat. Author(s): Merkx J. Source: Behavioural Brain Research. 1984 January; 11(1): 59-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6538089

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Effect of dihydrotestosterone on the rate of ethanol elimination in healthy men. Author(s): Vaubourdolle M, Guechot J, Chazouilleres O, Poupon RE, Giboudeau J. Source: Alcoholism, Clinical and Experimental Research. 1991 March; 15(2): 238-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1905499

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Effect of free fatty acids on the bioavailability of plasma testosterone and dihydrotestosterone. Author(s): Mooradian AD, Pamplona DM, Viosca SP, Korenman SG. Source: J Steroid Biochem. 1988 March; 29(3): 369-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3357342

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Effect of MK-386, a novel inhibitor of type 1 5 alpha-reductase, alone and in combination with finasteride, on serum dihydrotestosterone concentrations in men. Author(s): Schwartz JI, Van Hecken A, De Schepper PJ, De Lepeleire I, Lasseter KC, Shamblen EC, Winchell GA, Constanzer ML, Chavez CM, Wang DZ, Ebel DL, Justice SJ, Gertz BJ. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 August; 81(8): 2942-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8768856

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Effect of orchidectomy on serum concentrations of testosterone and dihydrotestosterone in patients with prostatic cancer. Author(s): Rohl HF, Beuke HP. Source: Scandinavian Journal of Urology and Nephrology. 1992; 26(1): 11-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1631501

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Effect of parathyroid hormone related protein, and dihydrotestosterone on proliferation and ornithine decarboxylase mRNA in human prostate cancer cell lines. Author(s): Asadi F, Faraj M, Malakouti S, Kukreja SC. Source: International Urology and Nephrology. 2001; 33(3): 417-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12230264

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Effect of tamoxifen pre-treatment on the retention of tritiated oestradiol and 5alphadihydrotestosterone and on glucose metabolism in human breast carcinomas. Author(s): Deshpande N, Mitchell I, Hughes D. Source: European Journal of Cancer (Oxford, England : 1990). 1978 May; 14(5): 473-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=148360

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Effect of zinc administration on plasma testosterone, dihydrotestosterone, and sperm count. Author(s): Netter A, Hartoma R, Nahoul K. Source: Archives of Andrology. 1981 August; 7(1): 69-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7271365

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Effects of 10 days administration of percutaneous dihydrotestosterone on the pituitary-testicular axis in normal men. Author(s): Kuhn JM, Rieu M, Laudat MH, Forest MG, Pugeat M, Bricaire H, Luton JP. Source: The Journal of Clinical Endocrinology and Metabolism. 1984 February; 58(2): 231-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6363434

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Effects of castration compared with total androgen blockade on tissue dihydrotestosterone (DHT) concentration in benign prostatic hyperplasia (BPH). Author(s): Geller J, Albert J. Source: Urological Research. 1987; 15(3): 151-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3629749

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Effects of dihydrotestosterone and hydroxyflutamide on androgen receptors in cultured human breast cancer cells (EVSA-T). Author(s): Marugo M, Bernasconi D, Miglietta L, Fazzuoli L, Ravera F, Cassulo S, Giordano G. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1992 June; 42(5): 547-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1616884

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Effects of dihydrotestosterone on LH release induced by LH-RH in men. Author(s): D'Agata R, Gulizia S, Ando S, Polosa P. Source: Acta Endocrinol (Copenh). 1975 May; 79(1): 1-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1093346

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Effects of dihydrotestosterone, 17 beta-estradiol and dexamethasone on mitogen--and allogeneic--induced lymphoblastogenesis. Author(s): Ow KT, Abandowitz HM, Sarfaty GA, Nash AR. Source: Endocrinol Exp. 1983 March; 17(1): 69-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6603351

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Effects of extracellular matrix components and dihydrotestosterone on the structure and function of human prostate cancer cells. Author(s): Murphy BC, Pienta KJ, Coffey DS. Source: The Prostate. 1992; 20(1): 29-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1371008

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Effects of pharmacological doses of testosterone and dihydrotestosterone on the hypothalamic-pituitary axis function of Klinefelter patients. Author(s): Forti G, Vannucchi PL, Borghi A, Giusti G, Fusi S, Serio M. Source: J Endocrinol Invest. 1983 August; 6(4): 297-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6417219

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Effects of tamoxifen on the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), 17 beta-oestradiol (E2), total and free testosterone (T) and total and free dihydrotestosterone (DHT) in blood of patients with benign prostatic hyperplasia. Author(s): Stahl F, Schnorr D, Rohde W, Poppe I, Geier T, Dorner G. Source: Exp Clin Endocrinol. 1983 July; 82(1): 21-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6193975

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Effects of testosterone, dihydrotestosterone and estradiol on growth of human hair outer root sheath keratinocytes in vitro. Author(s): Kiesewetter F, Arai A, Hintzenstern J, Schell H. Source: Archives of Dermatological Research. 1991; 283(7): 476-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1801659

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Effects of the testosterone metabolite dihydrotestosterone and 5 alpha-androstan-3 alpha,17 beta-diol on very long chain fatty acid metabolism in Xadrenoleukodystrophic fibroblasts. Author(s): Petroni A, Blasevich M, Uziel G. Source: Life Sciences. 2003 August 8; 73(12): 1567-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865096

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Effects of two different medical treatments on dihydrotestosterone content and androgen receptors in human benign prostatic hyperplasia. Author(s): Petrangeli E, Sciarra F, Di Silverio F, Toscano V, Lubrano C, Conti C, Concolino G. Source: J Steroid Biochem. 1988; 30(1-6): 395-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2455099

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Enzymatic conversion of dihydrotestosterone from 3-keto to 3-enol form in the rat prostate. Author(s): Kouretas D, Voyatzi S, Sahpazidou D, Lazopoulos K, Antonoglou O. Source: Anticancer Res. 1996 September-October; 16(5A): 2843-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8917395

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Epidermal keratinocytes: a source of 5 alpha-dihydrotestosterone production in human skin. Author(s): Milewich L, Kaimal V, Shaw CB, Sontheimer. Source: The Journal of Clinical Endocrinology and Metabolism. 1986 April; 62(4): 739-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3949953

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Estimating the contribution of the prostate to blood dihydrotestosterone. Author(s): Toorians AW, Kelleher S, Gooren LJ, Jimenez M, Handelsman DJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5207-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602751

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Estramustine-binding protein to dihydrotestosterone ratio in human prostatic carcinoma: a new marker for predicting disease progression. Author(s): Shiina H, Igawa M, Ishibe T. Source: British Journal of Urology. 1996 January; 77(1): 96-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8653325

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Estrogen-stimulated glucuronidation of dihydrotestosterone in MCF-7 human breast cancer cells. Author(s): Roy R, Dauvois S, Labrie F, Belanger A. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1992 March; 41(3-8): 579-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1562529

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Evidence for a specific dihydrotestosterone-binding cytosol receptor in the human prostate. Author(s): Geller J, Cantor T, Albert J. Source: The Journal of Clinical Endocrinology and Metabolism. 1975 November; 41(5): 854-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=52654

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Evidence for androgen receptor gene expression and growth inhibitory effect of dihydrotestosterone on human adrenocortical cells. Author(s): Rossi R, Zatelli MC, Valentini A, Cavazzini P, Fallo F, del Senno L, degli Uberti EC. Source: The Journal of Endocrinology. 1998 December; 159(3): 373-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9834454

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Evidence for receptor-dependent response to dihydrotestosterone in cultured human fibroblasts. Author(s): Ozasa H, Tominaga T, Nishimura T, Takeda T. Source: Endokrinologie. 1981 April; 77(2): 129-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7262037

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Familial external genital ambiguity due to a transformation defect of androgenreceptor complexes that is expressed with 5 alpha-dihydrotestosterone and the synthetic androgen methyltrienolone. Author(s): Kaufman M, Pinsky L, Bowin A, Au MW. Source: American Journal of Medical Genetics. 1984 July; 18(3): 493-507. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6332533

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Familial incomplete male pseudohermaphroditism, type 2. Decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. Author(s): Walsh PC, Madden JD, Harrod MJ, Goldstein JL, MacDonald PC, Wilson JD. Source: The New England Journal of Medicine. 1974 October 31; 291(18): 944-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4413434

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Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia. Author(s): McConnell JD, Wilson JD, George FW, Geller J, Pappas F, Stoner E. Source: The Journal of Clinical Endocrinology and Metabolism. 1992 March; 74(3): 505-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1371291

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Fluoroimmunoassay of 5alpha-dihydrotestosterone. Author(s): Exley D, Ekeke GI. Source: J Steroid Biochem. 1981 December; 14(12): 1297-302. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7329064

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Formation and degradation of dihydrotestosterone by recombinant members of the rat 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase family. Author(s): Sanchez R, de Launoit Y, Durocher F, Belanger A, Labrie F, Simard J. Source: Molecular and Cellular Endocrinology. 1994 July; 103(1-2): 29-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7958395

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Formation of dihydrotestosterone and other 5 alpha-reduced metabolites by isolated seminiferous tubules and suspension of interstitial cells in a human testis. Author(s): Payne AH, Kawano A, Jaffe RB. Source: The Journal of Clinical Endocrinology and Metabolism. 1973 September; 37(3): 448-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4150444

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Further studies on the effects of dihydrotestosterone on gonadotrophin release induced by LH-RH in men. Author(s): Ando S, Polosa P, D'Agata R. Source: Clinical Endocrinology. 1978 December; 9(6): 557-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=371861

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Gonadal and peripheral venous levels of dihydrotestosterone in a patient with testicular feminization. Author(s): Wieland RG, Chen JC, Zorn EM, Webster KD, Tang PH. Source: The Journal of Laboratory and Clinical Medicine. 1971 November; 78(5): 825. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5128868

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Heroin addiction: relationship between the plasma levels of testosterone, dihydrotestosterone, androstenedione, LH, FSH, and the plasma concentration of heroin. Author(s): Bolelli G, Lafisca S, Flamigni C, Lodi S, Franceschetti F, Filicori M, Mosca R. Source: Toxicology. 1979 December; 15(1): 19-29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=120622

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Heterogeneity in androgen receptor levels and growth response to dihydrotestosterone in sublines derived from human hepatocellular carcinoma line (KYN-1). Author(s): Yu L, Kubota H, Imai K, Yamaguchi M, Nagasue N. Source: Liver. 1997 February; 17(1): 35-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9062878

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High efficiency covalent radiolabeling of the human androgen receptor. Studies in cultured fibroblasts using dihydrotestosterone 17 beta-bromoacetate. Author(s): Kovacs WJ, Turney MK. Source: The Journal of Clinical Investigation. 1988 February; 81(2): 342-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3339123

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Hormonal consequences of orchidectomy for carcinoma of the prostate. With special reference to the measurement of free testosterone in saliva and prostatic dihydrotestosterone levels. Author(s): Boccon-Gibod L, Laudat MH, Guiban D, Steg A. Source: European Urology. 1988; 15(1-2): 99-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3215246

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Human complete androgen insensitivity with normal dihydrotestosterone receptor binding capacity in cultured genital skin fibroblasts: evidence for a qualitative abnormality of the receptor. Author(s): Brown TR, Maes M, Rothwell SW, Migeon CJ. Source: The Journal of Clinical Endocrinology and Metabolism. 1982 July; 55(1): 61-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7076808

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Human male sexual functions do not require aromatization of testosterone: a study using tamoxifen, testolactone, and dihydrotestosterone. Author(s): Gooren LJ. Source: Archives of Sexual Behavior. 1985 December; 14(6): 539-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4084053

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Human minimal androgen insensitivity with normal dihydrotestosterone-binding capacity in cultured genital skin fibroblasts: evidence for an androgen-selective qualitative abnormality of the receptor. Author(s): Pinsky L, Kaufman M, Killinger DW, Burko B, Shatz D, Volpe R. Source: American Journal of Human Genetics. 1984 September; 36(5): 965-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6333813

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71

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In vitro effects of testosterone, dihydrotestosterone and estradiol on cell growth of human hair bulb papilla cells and hair root sheath fibroblasts. Author(s): Arai A, von Hintzenstern J, Kiesewetter F, Schell H, Hornstein OP. Source: Acta Dermato-Venereologica. 1990; 70(4): 338-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1977261

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In vitro evaluation of 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)urea linked to 4acetoxy-bisdesmethyltamoxifen, estradiol and dihydrotestosterone. Author(s): Kaleagasioglu F, Berger MR, Schmahl D, Eisenbrand G. Source: Arzneimittel-Forschung. 1990 May; 40(5): 603-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2383304

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In vitro studies of testosterone and 5alpha-dihydrotestosterone binding in benign prostatic hypertrophy. Author(s): Steins P, Krieg M, Hollmann HJ, Voigt KD. Source: Acta Endocrinol (Copenh). 1974 April; 75(4): 773-84. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4136809

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In vitro uptake of 3H testosterone and its conversion to dihydrotestosterone by prostatic carcinoma and other tissues. Author(s): Prout GR Jr, Kliman B, Daly JJ, Maclaughlin RA, Griffin PP. Source: The Journal of Urology. 1976 November; 116(5): 603-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=62062

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In vivo uptake and metabolism of 3H-testosterone and 3H-5 -dihydrotestosterone by human benign prostatic hypertrophy. Author(s): Becker H, Kaufmann J, Klosterhalfen H, Voigt KD. Source: Acta Endocrinol (Copenh). 1972 November; 71(3): 589-99. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4117573

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Incomplete testicular feminization syndrome: studies of 17 beta-oestradiol-binding activity and aromatase activity in cultured genital fibroblasts showing impaired dihydrotestosterone-binding. Author(s): Imai A, Ohno T, Nakagawa M, Sawairi M, Tamaya T. Source: Annals of Clinical Biochemistry. 1992 March; 29 ( Pt 2): 153-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1626917

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Increased dihydrotestosterone receptor levels in high-stage renal adenocarcinoma. Author(s): Noronha RF, Rao BR. Source: Cancer. 1985 July 1; 56(1): 134-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4005782

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Indirect growth inhibition of the MDA-MB-231 hormone-independent breast cancer cell line by dihydrotestosterone. Author(s): Gatto V, Di Monaco M, Brignardello E, Leonardi L, Gallo M, Boccuzzi G. Source: Annals of the New York Academy of Sciences. 1996 April 30; 784: 439-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8651594

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Influence of dihydrotestosterone, epidermal growth factor, and basic fibroblast growth factor on the cell kinetics of the PC3, DU145, and LNCaP prostatic cancer cell lines: relationship with DNA ploidy level. Author(s): Janssen T, Kiss R, Dedecker R, Petein M, Pasteels JL, Schulman C. Source: The Prostate. 1995 November; 27(5): 277-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7479395

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Influences of dihydrotestosterone, testosterone, estradiol, progesterone, or prolactin on the cell kinetics of human hyperplastic prostatic tissue in organ culture. Author(s): de Launoit Y, Kiss R, Jossa V, Coibion M, Paridaens RJ, De Backer E, Danguy AJ, Pasteels JL. Source: The Prostate. 1988; 13(2): 143-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2459683

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Inhibition by various steroids on dihydrotestosterone binding to androphilic protein in human benign prostatic hypertrophy. Author(s): Kodama T, Honda S, Shimazaki J. Source: Endocrinol Jpn. 1978 October; 25(5): 453-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=84756

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Inhibition of 5 alpha-reductase activity and alteration of nuclear testosterone. Dihydrotestosterone ratio in human genital skin fibroblasts. Author(s): Berkovitz GD, Brown TR, Migeon CJ. Source: Journal of Andrology. 1984 May-June; 5(3): 171-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6746410

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Inhibition of NFkappaB activity through maintenance of IkappaBalpha levels contributes to dihydrotestosterone-mediated repression of the interleukin-6 promoter. Author(s): Keller ET, Chang C, Ershler WB. Source: The Journal of Biological Chemistry. 1996 October 18; 271(42): 26267-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8824277

Studies

73

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Inhibition of testosterone conversion to dihydrotestosterone in men treated percutaneously by progesterone. Author(s): Mauvais-Jarvis P, Kuttenn F, Baudot N. Source: The Journal of Clinical Endocrinology and Metabolism. 1974 January; 38(1): 1427. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4809637

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Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor. Author(s): Cheng S, Brzostek S, Lee SR, Hollenberg AN, Balk SP. Source: Molecular Endocrinology (Baltimore, Md.). 2002 July; 16(7): 1492-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12089345

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Inhibitory effect of dihydrotestosterone on human thyroid cell growth. Author(s): Rossi R, Zatelli MC, Franceschetti P, Maestri I, Magri E, Aguiari G, Cavazzini P, degli Uberti EC, del Senno L. Source: The Journal of Endocrinology. 1996 November; 151(2): 185-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8958778

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Insulin-like growth factor binding protein-3 is regulated by dihydrotestosterone and stimulates deoxyribonucleic acid synthesis and cell proliferation in LNCaP prostate carcinoma cells. Author(s): Martin JL, Pattison SL. Source: Endocrinology. 2000 July; 141(7): 2401-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10875240

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Interaction of delta-5-androstene-3beta, 17beta-diol with estradiol and dihydrotestosterone receptors in human myometrial and mammary cancer tissue. Author(s): Poortman J, Prenen JA, Schwarz F, Thijssen JH. Source: The Journal of Clinical Endocrinology and Metabolism. 1975 March; 40(3): 373-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=163841

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Interrelationships between sex hormone-binding globulin and 17 beta-estradiol, testosterone, 5 alpha-dihydrotestosterone, thyroxine, and triiodothyronine in prepubertal and pubertal girls. Author(s): Bartsch W, Horst HJ, Derwahl DM. Source: The Journal of Clinical Endocrinology and Metabolism. 1980 June; 50(6): 1053-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7189524

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Interrelationships between sex hormone-binding globulin and testosterone, 5 alphadihydrotestosterone and oestradiol-17 beta in blood of normal men. Author(s): Bartsch W. Source: Maturitas. 1980 July; 2(2): 109-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7193795

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Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. II. C18 and C19 steroids: estradiol, estriol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, delta 5-androstenediol, delta 4-androstenedione, testosterone, and dihydrotestosterone. Author(s): Buster JE, Chang RJ, Preston DL, Elashoff RM, Cousins LM, Abraham GE, Hobel CJ, Marshall JR. Source: The Journal of Clinical Endocrinology and Metabolism. 1979 January; 48(1): 13942. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=154525

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Intracellular localisation of 5alpha-dihydrotestosterone in human benign prostatic hypertrophy. Author(s): Ghanadian R, Chisholm GD, Fotherby K. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1976 December; 73(3): 521-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=63340

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Intramuscular administration of 5 alpha-dihydrotestosterone heptanoate: changes in urinary hormone profile. Author(s): Coutts SB, Kicman AT, Hurst DT, Cowan DA. Source: Clinical Chemistry. 1997 November; 43(11): 2091-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9365393

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Intrinsic regional differences in androgen receptors and dihydrotestosterone metabolism in human preadipocytes. Author(s): Joyner J, Hutley L, Cameron D. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2002 May; 34(5): 223-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12063633

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Investigations into the use of 77Br labelled 5alpha-dihydrotestosterone for scanning the prostate. Author(s): Ghanadian R, Waters SL, Chisholm GD. Source: European Journal of Nuclear Medicine. 1977 September 30; 2(3): 155-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=913428

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In-vitro contractility of human seminiferous tubules in response to testosterone, dihydrotestosterone and estradiol. Author(s): Yamamoto M, Nagai T, Takaba H, Hashimoto J, Miyake K. Source: Urological Research. 1989; 17(4): 265-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2773191

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In-vitro studies on testosterone and 5alpha-dihydrotestosterone binding in benign prostatic hypertrophy (BPH). Author(s): Steins P, Hollmann HJ, Schmidt H, Voigt KD. Source: Acta Endocrinol Suppl (Copenh). 1973; 173: 69. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4125280

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Involvement of p27Kip1 in G1 arrest by high dose 5 alpha-dihydrotestosterone in LNCaP human prostate cancer cells. Author(s): Tsihlias J, Zhang W, Bhattacharya N, Flanagan M, Klotz L, Slingerland J. Source: Oncogene. 2000 February 3; 19(5): 670-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10698512

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Is dihydrotestosterone a cause of follicular atresia? Author(s): Nandedkar TD. Source: Medical Hypotheses. 1981 June; 7(6): 801-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6792473

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Kinetics and effect of percutaneous administration of dihydrotestosterone in children. Author(s): Charmandari E, Dattani MT, Perry LA, Hindmarsh PC, Brook CG. Source: Hormone Research. 2001; 56(5-6): 177-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11910204

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Kinetics of 3H-5 -dihydrotestosterone metabolism in normal men and women and men with prostatic carcinoma; effects of estrogen administration in men. Author(s): Bird CE, Clark AF. Source: The Journal of Clinical Endocrinology and Metabolism. 1972 March; 34(3): 46772. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5011250

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Kinetics of 3H-testosterone and 3H-dihydrotestosterone metabolism in patients with benign prostatic hypertrophy. Effect of cyproterone acetate. Author(s): Hutschenreiter G, Sinterhauf K, Altwein JE. Source: European Urology. 1977; 3(2): 100-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=67948

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Lack of a synergistic effect between estradiol and dihydrotestosterone in the masculinization of the zebra finch song system. Author(s): Jacobs EC, Grisham W, Arnold AP. Source: Journal of Neurobiology. 1995 August; 27(4): 513-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7561830

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Lack of effect of topical finasteride suggests an endocrine role for dihydrotestosterone. Author(s): Price TM, Allen S, Pegram GV. Source: Fertility and Sterility. 2000 August; 74(2): 414-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10927075

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Life-long absence of sexual drive in a woman associated with 5-dihydrotestosterone deficiency. Author(s): Riley AJ. Source: Journal of Sex & Marital Therapy. 1999 January-March; 25(1): 73-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10081744

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Lignans interfering with 5 alpha-dihydrotestosterone binding to human sex hormonebinding globulin. Author(s): Schottner M, Spiteller G, Gansser D. Source: Journal of Natural Products. 1998 January; 61(1): 119-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9461660

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Locus on human X chromosome for dihydrotestosterone receptor and androgen insensitivity. Author(s): Meyer WJ 3rd, Migeon BR, Migeon CJ. Source: Proceedings of the National Academy of Sciences of the United States of America. 1975 April; 72(4): 1469-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=165510

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Long-term transdermal dihydrotestosterone therapy: effects on pituitary gonadal axis and plasma lipoproteins. Author(s): Vermeulen A, Deslypere JP. Source: Maturitas. 1985 September; 7(3): 281-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3935902

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Low dihydrotestosterone and weight loss in the AIDS wasting syndrome. Author(s): Sattler F, Briggs W, Antonipillai I, Allen J, Horton R. Source: Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association. 1998 July 1; 18(3): 246-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9665502

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Low serum testosterone/dihydrotestosterone ratio in patients with pancreatic carcinoma. Author(s): Robles-Diaz G, Diaz-Sanchez V, Mendez JP, Altamirano A, Wolpert E. Source: Pancreas. 1987; 2(6): 684-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3438305

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Luteinizing hormone pulsatility in subjects with 5-alpha-reductase deficiency and decreased dihydrotestosterone production. Author(s): Canovatchel WJ, Volquez D, Huang S, Wood E, Lesser ML, Gautier T, Imperato-McGinley J. Source: The Journal of Clinical Endocrinology and Metabolism. 1994 April; 78(4): 916-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8157721

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Luteinizing hormone, follicle-stimulating hormone, testosterone and dihydrotestosterone during testicular descent in the pig fetus. Author(s): Visser JH, Heyns CF. Source: Reproduction, Fertility, and Development. 1996; 8(7): 1115-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8916288

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Male pseudohermaphroditism presumably due to target organ unresponsiveness to androgens. Deficient 5alpha-dihydrotestosterone binding in cultured skin fibroblasts. Author(s): Kaufman M, Straisfeld C, Pinsky L. Source: The Journal of Clinical Investigation. 1976 August; 58(2): 345-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=182718

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Mass spectrometric identification of testosterone, androstenedione, dehydroepiandrosterone, dihydrotestosterone, and androstanediol in human peripheral plasma. Author(s): Ganjam VK, Murphy BE, Chan TH, Currie PA. Source: J Steroid Biochem. 1973 September; 4(5): 443-50. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4273817

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Measurement of plasma dihydrotestosterone by competitive protein-binding analysis. Author(s): Tremblay RR, Beitins IZ, Kowarski A, Migeon CJ. Source: Steroids. 1970 July; 16(1): 29-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5471534

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Measurement of unconjugated testosterone, 5alpha-dihydrotestosterone and oestradiol in human urine. Author(s): Kjeld JM, Puah CM, Joplin GF. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1977 October 15; 80(2): 271-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=562240

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Mechanisms of action of androgens and antiandrogens: effects of antiandrogens on translocation of cytoplasmic androgen receptor and nuclear abundance of dihydrotestosterone. Author(s): Callaway TW, Bruchovsky N, Rennie PS, Comeau T. Source: The Prostate. 1982; 3(6): 599-610. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7155992

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Metabolic clearance rate (MCR) of dehydroepiandrosterone sulfate (DS), its metabolism to dehydroepiandrosterone, androstenedione, testosterone, and dihydrotestosterone, and the effect of increased plasma DS concentration on DS MCR in normal women. Author(s): Haning RV Jr, Chabot M, Flood CA, Hackett R, Longcope C. Source: The Journal of Clinical Endocrinology and Metabolism. 1989 November; 69(5): 1047-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2529265

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Metabolic clearance rate and blood production rate of testosterone and dihydrotestosterone in normal subjects, during pregnancy, and in hyperthyroidism. Author(s): Saez JM, Forest MG, Morera AM, Bertrand J. Source: The Journal of Clinical Investigation. 1972 May; 51(5): 1226-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5020435

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Metabolic clearance rate of dehydroepiandrosterone sulfate, its metabolism to testosterone, and its intrafollicular metabolism to dehydroepiandrosterone, androstenedione, testosterone, and dihydrotestosterone in vivo. Author(s): Haning RV Jr, Flood CA, Hackett RJ, Loughlin JS, McClure N, Longcope C. Source: The Journal of Clinical Endocrinology and Metabolism. 1991 May; 72(5): 1088-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1827126

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Metabolism in vitro of dihydrotestosterone, 5alpha-androstane 3alpha, 17beta-diol and its 3beta-epimer, three metabolites of testosterone, by three of its target tissues, the anterior pituitary, the medial basal hypothalamus and the seminiferous tubules. Author(s): Kao LW, Lloret AP, Weisz J. Source: J Steroid Biochem. 1977 October; 8(10): 1109-15. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=916667

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Metabolism of 5alpha-dihydrotestosterone in human benign hyperplastic prostate. Author(s): Malathi K, Gurpide E. Source: J Steroid Biochem. 1977 February; 8(2): 141-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=68174

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Metabolism of dihydrotestosterone in human liver: importance of 3alpha- and 3betahydroxysteroid dehydrogenase. Author(s): Pirog EC, Collins DC. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 September; 84(9): 3217-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10487690

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Metabolism of dihydrotestosterone to 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide is greater in the peripheral compartment than in the splanchnic compartment. Author(s): Duffy DM, Legro RS, Chang L, Stanczyk FZ, Lobo RA. Source: Fertility and Sterility. 1995 October; 64(4): 736-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7672144

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Metabolism of testosterone and dihydrotestosterone in the hirsute female. Author(s): Concolino G, Marocchi A, Sciarra F, Sorcini G. Source: Folia Endocrinol. 1973 August; 26(4): 293-307. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4801004

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Microautoradiographic studies on distribution of 5 alpha-dihydrotestosterone, cyproterone acetate and oestradiol-17 beta in human prostatic hyperplasia tissue transplanted to juvenile rats. Author(s): Ruberg I, Senge T, Neumann F. Source: Acta Endocrinol (Copenh). 1982 September; 101(1): 144-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6181639

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MK-386, an inhibitor of 5alpha-reductase type 1, reduces dihydrotestosterone concentrations in serum and sebum without affecting dihydrotestosterone concentrations in semen. Author(s): Schwartz JI, Tanaka WK, Wang DZ, Ebel DL, Geissler LA, Dallob A, Hafkin B, Gertz BJ. Source: The Journal of Clinical Endocrinology and Metabolism. 1997 May; 82(5): 1373-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9141518

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Modulation of sensitivity to transforming growth factor-beta 1 (TGF-beta 1) and the level of type II TGF-beta receptor in LNCaP cells by dihydrotestosterone. Author(s): Kim IY, Zelner DJ, Sensibar JA, Ahn HJ, Park L, Kim JH, Lee C. Source: Experimental Cell Research. 1996 January 10; 222(1): 103-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8549651

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Molecular biology of androgen action: testosterone/dihydrotestosterone receptor and androgen 5 alpha-reductase in the human foreskin. Author(s): Herkner K, Swoboda W, Hoeller B, Goedl U. Source: J Steroid Biochem. 1986 January; 24(1): 239-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3702407

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Nitric oxide in the human hair follicle: constitutive and dihydrotestosterone-induced nitric oxide synthase expression and NO production in dermal papilla cells. Author(s): Wolf R, Schonfelder G, Paul M, Blume-Peytavi U. Source: Journal of Molecular Medicine (Berlin, Germany). 2003 February; 81(2): 110-7. Epub 2002 December 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12601527

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Non-chromatographic radioimmunoassays for testosterone and 5 alphadihydrotestosterone in adult female serum using antisera with low cross-reactivities. Author(s): Tateishi K, Hamaoka T, Hayashi C. Source: J Steroid Biochem. 1980 August; 13(8): 869-72. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7464133

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Oestradiol- and dihydrotestosterone receptors in normal and neoplastic human mammary tissue. Author(s): Wagner RK, Jungblut PW. Source: Acta Endocrinol (Copenh). 1976 May; 82(1): 105-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=178132

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On the role of dihydrotestosterone in regulating luteinizing hormone secretion in man. Author(s): Schaison G, Renoir M, Lagoguey M, Mowszowicz I. Source: The Journal of Clinical Endocrinology and Metabolism. 1980 November; 51(5): 1133-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6106650

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Osteoblast gene expression in rat long bones: effects of ovariectomy and dihydrotestosterone on mRNA levels. Author(s): Davey RA, Hahn CN, May BK, Morris HA. Source: Calcified Tissue International. 2000 July; 67(1): 75-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10908417

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Percutaneous absorption of 5 alpha-dihydrotestosterone in man. I. Plasma androgen and gonadotrophin levels in normal adult men after percutaneous administration of 5 alpha-dihydrotestosterone. Author(s): Fiet J, Morville R, Chemama D, Villette JM, Gourmel B, Brerault JL, Dreux C. Source: International Journal of Andrology. 1982 December; 5(6): 586-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6819234

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Percutaneous absorption of 5 alpha-dihydrotestosterone in man. II. Percutaneous administration of 5 alpha-dihydrotestosterone in hypogonadal men with idiopathic haemochromatosis; clinical, metabolic and hormonal effectiveness. Author(s): Chemana D, Morville R, Fiet J, Villette JM, Tabuteau F, Brerault JL, Passa P. Source: International Journal of Andrology. 1982 December; 5(6): 595-606. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7160922

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P-glycoprotein increases the efflux of the androgen dihydrotestosterone and reduces androgen responsive gene activity in prostate tumor cells. Author(s): Fedoruk MN, Gimenez-Bonafe P, Guns ES, Mayer LD, Nelson CC. Source: The Prostate. 2004 April 1; 59(1): 77-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991868

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Phenotypic variation in a family with partial androgen insensitivity syndrome explained by differences in 5alpha dihydrotestosterone availability. Author(s): Boehmer AL, Brinkmann AO, Nijman RM, Verleun-Mooijman MC, de Ruiter P, Niermeijer MF, Drop SL. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 March; 86(3): 12406. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11238515

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Plasma and salivary androstenedione and dihydrotestosterone in women with hyperandrogenism. Author(s): Baxendale PM, Jacobs HS, James VH. Source: Clinical Endocrinology. 1983 May; 18(5): 447-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6223726

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Plasma androgens in hirsute females. IV. Determination of blood testosterone androstenedione, dihydrotestosterone and delta5-androstenediol. Author(s): Sciarra F, Toscano V, Concolino G, Sorcini G, Conti C. Source: Folia Endocrinol. 1974 December; 27(6Pt2): 663-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4480664

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Plasma concentrations of testosterone and dihydrotestosterone during the mestrual cycle of women affected by simple hirsutism. II. Author(s): Sciarra F, Concolino G, Sorcini G, Toscano V. Source: Folia Endocrinol. 1973 August; 26(4): 288-92. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4801003

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Plasma dihydrotestosterone in normal adult males and its relation to testosterone. Author(s): Pirke KM, Doerr P. Source: Acta Endocrinol (Copenh). 1975 June; 79(2): 357-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1173494

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Plasma pregnenolone, progesterone, 17-hydroxyprogesterone, testosterone and 5alpha-dihydrotestosterone in different types of congenital adrenal hyperplasia. Author(s): Janne O, Perheentupa J, Viinikka L, Vihko R. Source: Clinical Endocrinology. 1975 January; 4(1): 39-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1122653

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Plasma testosterone and dihydrotestosterone in normal and abnormal pregnancy. Author(s): Tajic M, Gerencer M, Kastelan A. Source: Experientia. 1981 April 15; 37(4): 427-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7238834

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Plasma testosterone and dihydrotestosterone in ovulatory and anovulatory cycles. Author(s): Dawood MY, Saxena BB. Source: American Journal of Obstetrics and Gynecology. 1976 October 15; 126(4): 430-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=984104

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Plasma testosterone, sex hormone binding globulin binding capacity and per cent binding of testosterone and 5alpha-dihydrotestosterone in prepubertal, pubertal and adult males. Author(s): Horst HJ, Bartsch W, Dirksen-Thiedens I. Source: The Journal of Clinical Endocrinology and Metabolism. 1977 September; 45(3): 522-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=561806

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Polycaprolactone-b-poly(ethylene oxide) copolymer micelles as a delivery vehicle for dihydrotestosterone. Author(s): Allen C, Han J, Yu Y, Maysinger D, Eisenberg A. Source: Journal of Controlled Release : Official Journal of the Controlled Release Society. 2000 February 3; 63(3): 275-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10601723

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83

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Possible implications of the comparative dissociative behavior of testosterone- and 5 alpha-dihydrotestosterone-receptor complexes formed by human skin fibroblasts. Author(s): Kaufman M, Pinsky L, Schwartz A, Long-Simpson L. Source: J Steroid Biochem. 1983 July; 19(1B): 561-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6887884

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Possible indices for the detection of the administration of dihydrotestosterone to athletes. Author(s): Southan GJ, Brooks RV, Cowan DA, Kicman AT, Unnadkat N, Walker CJ. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1992 March; 42(1): 87-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1558821

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Preparation and antigenic properties of 5alpha-dihydrotestosterone-15alpha-bovine serum albumin conjugate. Author(s): Nambara T, Hosoda H, Tadano K, Yamashita K. Source: Chemical & Pharmaceutical Bulletin. 1978 December; 26(12): 3851-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=570888

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Preponderance of serum and intra-hepatic 5 alpha-dihydrotestosterone in males with hepatocellular carcinoma despite low circulating androgen levels. Author(s): Iqbal MJ, Wilkinson ML, Forbes A, Corbishley TP, Williams R. Source: Journal of Hepatology. 1986; 3(3): 304-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3031151

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Proceedings: Age-related changes in serum 5alpha-dihydrotestosterone and testosterone in normal men. Author(s): Lewis JG, Ghanadian R, Chisholm GD. Source: The Journal of Endocrinology. 1975 November; 67(2): 15P. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1206265

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Proceedings: Binding of 5 alpha-dihydrotestosterone in human prostatic cancer; examination by agar gel electrophoresis. Author(s): Nijs M, Hawkins EF, Coune A. Source: The Journal of Endocrinology. 1976 June; 69(3): 18P-19P. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=950511

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Proceedings: Influences of oestradiol benzoate given alone or in conjunction with dihydrotestosterone on isolation-induced fighting behaviour in castrated TO strain mice. Author(s): Brain PF, Poole AE. Source: The Journal of Endocrinology. 1975 June; 65(3): 37P-38P. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1171153

84

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Proceedings: Novel procedure for the simultaneous determination of testosterone and 5alpha-dihydrotestosterone concentrations in unpurified plasma extracts by radioimmunoassay. Author(s): Llewelyn DE, Read GF, Hillier SG. Source: The Journal of Endocrinology. 1975 November; 67(2): 7P-8P. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1206320

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Production and metabolism of dihydrotestosterone in peripheral tissues. Author(s): Longcope C, Fineberg SE. Source: J Steroid Biochem. 1985 October; 23(4): 415-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4068703

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Production and purification of histidine-tagged dihydrotestosterone-bound fulllength human androgen receptor. Author(s): Liao M, Wilson EM. Source: Methods in Molecular Biology (Clifton, N.J.). 2001; 176: 67-79. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11554339

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Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/dilution and mass spectrometry. Author(s): Vierhapper H, Nowotny P, Maier H, Waldhausl W. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 December; 86(12): 5762-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11739436

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Production rates of testosterone and of dihydrotestosterone in female pattern hair loss. Author(s): Vierhapper H, Maier H, Nowotny P, Waldhausl W. Source: Metabolism: Clinical and Experimental. 2003 July; 52(7): 927-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12870172

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Progesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone and androsterone concentrations in specific regions of the human brain. Author(s): Hammond GL, Hirvonen J, Vihko R. Source: J Steroid Biochem. 1983 February; 18(2): 185-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6843122

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85

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Prostate cancer and polymorphism D85Y in gene for dihydrotestosterone degrading enzyme UGT2B15: Frequency of DD homozygotes increases with Gleason Score. Author(s): Hajdinjak T, Zagradisnik B. Source: The Prostate. 2004 June 1; 59(4): 436-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15065092

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Protection of 5alpha-dihydrotestosterone against TGF-beta-induced apoptosis in FaO cells and induction of mitosis in HepG2 cells. Author(s): Lim IK, Joo HJ, Choi KS, Sueoka E, Lee MS, Ryu MS, Fujiki H. Source: International Journal of Cancer. Journal International Du Cancer. 1997 July 17; 72(2): 351-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9219845

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Purification and properties of the 5 alpha-dihydrotestosterone 3 alpha(beta)hydroxysteroid dehydrogenase from human prostatic cytosol. Author(s): Trapp T, Tunn S, Krieg M. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1992 May; 42(3-4): 321-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1606044

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Pyridine nucleotide levels under conditions of 5 alpha-dihydrotestosteronestimulated 17 beta-estradiol formation from estrone and pathway of nicotinamide adenine dinucleotide biosynthesis in placental villi in vitro. Author(s): Blomquist CH, Hakanson EY. Source: The Journal of Clinical Endocrinology and Metabolism. 1991 July; 73(1): 140-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1828470

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Radioautographic demonstration of dihydrotestosterone receptor in cultured human fibroblasts. Author(s): Ozasa H, Tominaga T, Nishimura T, Takeda T. Source: Experientia. 1980 October 15; 36(10): 1230-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7418816

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Radioimmunoassay of plasma dihydrotestosterone in normal and hypogonodal men. Author(s): Pazzagli M, Forti G, Cappellini A, Serio M. Source: Clinical Endocrinology. 1975 September; 4(5): 513-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1175312

86

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Rapid and reliable separation of 5 alpha-dihydrotestosterone from testosterone on silica gel microcolumns. Author(s): Hamalainen EK, Fotsis T, Adlercreutz H. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1984 May 30; 139(2): 173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6329556

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Rapid HPLC-electrospray tandem mass spectrometric assay for urinary testosterone and dihydrotestosterone glucuronides from patients with benign prostate hyperplasia. Author(s): Choi MH, Kim JN, Chung BC. Source: Clinical Chemistry. 2003 February; 49(2): 322-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12560362

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Re: Early and late long-term effects of vasectomy on serum testosterone, dihydrotestosterone, luteinizing hormone and follicle-stimulating hormone levels. Author(s): Kliesch S, Roth S, Hertle L. Source: The Journal of Urology. 1996 November; 156(5): 1784-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8863615

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Reduced affinity of the androgen receptor for 5 alpha-dihydrotestosterone but not methyltrienolone in a form of partial androgen resistance. Studies on cultured genital skin fibroblasts. Author(s): Pinsky L, Kaufman M, Chudley AE. Source: The Journal of Clinical Investigation. 1985 April; 75(4): 1291-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3872888

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Reduced production rates of testosterone and dihydrotestosterone in healthy men treated with rosiglitazone. Author(s): Vierhapper H, Nowotny P, Waldhausl W. Source: Metabolism: Clinical and Experimental. 2003 February; 52(2): 230-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12601638

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Reduction of testosterone to 5 alpha-dihydrotestosterone by human and rat uterine tissues. Author(s): Rose LI, Reddy VV, Biondi R. Source: The Journal of Clinical Endocrinology and Metabolism. 1978 May; 46(5): 766-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=262766

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Regional distribution of epidermal growth factor, testosterone and dihydrotestosterone in benign prostatic hyperplasia tissue. Author(s): Sciarra F, Monti S, Adamo MV, Palma E, Toscano V, d'Eramo G, di Silverio F. Source: Urological Research. 1995; 23(6): 387-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8788277

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Regulation of Bcl-2 expression by dihydrotestosterone in hormone sensitive LNCaPFGC prostate cancer cells. Author(s): Bruckheimer EM, Spurgers K, Weigel NL, Logothetis C, McDonnell TJ. Source: The Journal of Urology. 2003 April; 169(4): 1553-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12629413

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Regulation of gonadotropin-releasing hormone (GnRH) gene expression by 5alphadihydrotestosterone in GnRH-secreting GT1-7 hypothalamic neurons. Author(s): Belsham DD, Evangelou A, Roy D, Duc VL, Brown TJ. Source: Endocrinology. 1998 March; 139(3): 1108-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9492044

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Regulation of human placental 17 beta-hydroxysteroid oxidoreductase: mechanism of stimulation of 17 beta-estradiol formation from estrone by 5 alphadihydrotestosterone in homogenates and villi in vitro. Author(s): Blomquist CH, Hakanson EY. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1991 November; 39(5A): 735-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1659869

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Regulation of proliferation and production of prostate-specific antigen in androgensensitive prostatic cancer cells, LNCaP, by dihydrotestosterone. Author(s): Lee C, Sutkowski DM, Sensibar JA, Zelner D, Kim I, Amsel I, Shaw N, Prins GS, Kozlowski JM. Source: Endocrinology. 1995 February; 136(2): 796-803. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7530653

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Regulation of prostate-specific antigen gene expression in LNCaP human prostatic carcinoma cells by growth, dihydrotestosterone, and extracellular matrix. Author(s): Guo Y, Pili R, Passaniti A. Source: The Prostate. 1994; 24(1): 1-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7507237

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Relationship between human prostatic epithelial cell protein synthesis and tissue dihydrotestosterone level. Author(s): Geller J, Liu J, Albert J, Fay W, Berry CC, Weis P. Source: Clinical Endocrinology. 1987 February; 26(2): 155-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3665114

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Relationship between plasma testosterone and dihydrotestosterone concentrations and male facial hair growth. Author(s): Farthing MJ, Mattei AM, Edwards CR, Dawson AM. Source: The British Journal of Dermatology. 1982 November; 107(5): 559-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7126460

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Relationships between oestradiol-17 beta, testosterone, dihydrotestosterone and 5 alpha-androstane-3 alpha, 27 beta-diol in human benign hypertrophy and carcinoma of the prostate. Author(s): Ghanadian R, Puah CM. Source: The Journal of Endocrinology. 1981 February; 88(2): 255-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6162906

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Response to cyproterone acetate treatment in primary hepatocellular carcinoma is related to fall in free 5 alpha-dihydrotestosterone. Author(s): Forbes A, Wilkinson ML, Iqbal MJ, Johnson PJ, Williams R. Source: Eur J Cancer Clin Oncol. 1987 November; 23(11): 1659-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2828073

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Response to local dihydrotestosterone treatment in a patient with partial androgeninsensitivity syndrome due to a novel mutation in the androgen receptor gene. Author(s): Foresta C, Bettella A, Ferlin A, Garolla A, Moro E, Baldinotti F, Simi P, Dallapiccola B. Source: American Journal of Medical Genetics. 2002 January 22; 107(3): 259-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11807912

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Response-surface modeling of the effect of 5alpha-dihydrotestosterone and androgen receptor levels on the response to the androgen antagonist vinclozolin. Author(s): Euling SY, Gennings C, Wilson EM, Kemppainen JA, Kelce WR, Kimmel CA. Source: Toxicological Sciences : an Official Journal of the Society of Toxicology. 2002 October; 69(2): 332-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377982

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Responsiveness of Dupuytren's disease fibroblasts to 5 alpha-dihydrotestosterone. Author(s): Pagnotta A, Specchia N, Soccetti A, Manzotti S, Greco F. Source: The Journal of Hand Surgery. 2003 November; 28(6): 1029-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14642522

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Role of dihydrotestosterone in androgen action. Author(s): Wilson JD. Source: Prostate Suppl. 1996; 6: 88-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8630237

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Role of testosterone and dihydrotestosterone in spontaneous gynecomastia of adolescents. Author(s): Villalpando S, Mondragon L, Barron C, Perez-Pasten E, Castaneda G, AlonsoUriarte R, Cortes-Gallegos V. Source: Archives of Andrology. 1992 May-June; 28(3): 171-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1530365

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Semiautomated method for the quantitation of plasma or sera androstenedione, testosterone, and dihydrotestosterone in population studies. Author(s): Walker VR, Dombi GW, Gutai JP, Wade DD, Swartz KH, Liu H, Schroeder RR. Source: Analytical Biochemistry. 1996 February 15; 234(2): 194-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8714598

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Seminal plasma testosterone and dihydrotestosterone levels in men with varicoceles. Author(s): Hudson RW, Hayes KA, Crawford VA, McKay DE. Source: International Journal of Andrology. 1983 April; 6(2): 135-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6862670

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Serum androgen bioactivity during 5alpha-dihydrotestosterone treatment in elderly men. Author(s): Raivio T, Tapanainen JS, Kunelius P, Janne OA. Source: Journal of Andrology. 2002 November-December; 23(6): 919-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12399539

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Serum dihydrotestosterone and testosterone concentrations in human immunodeficiency virus-infected men with and without weight loss. Author(s): Arver S, Sinha-Hikim I, Beall G, Guerrero M, Shen R, Bhasin S. Source: Journal of Andrology. 1999 September-October; 20(5): 611-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10520573

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Serum testosterone:dihydrotestosterone ratio and CA 19-9 in the diagnosis of pancreatic cancer. Author(s): Robles-Diaz G, Diaz-Sanchez V, Fernandez-del Castillo C, Morales M, Aceves G, Galvan E, Altamirano A. Source: The American Journal of Gastroenterology. 1991 May; 86(5): 591-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2028950

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Should the nonaromatizable androgen dihydrotestosterone be considered as an alternative to testosterone in the treatment of the andropause? Author(s): Wang C, Swerdloff RS. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 April; 87(4): 1462-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11932265

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Similarities between 5alpha-dihydrotestosterone-receptor complexes from human and rat prostatic tissue: effects on RNA polymerase activity. Author(s): Davies P, Griffiths K. Source: Molecular and Cellular Endocrinology. 1975 August; 3(2): 143-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=170152

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Simultaneous determination of testosterone, dihydrotestosterone and 5 alphaandrostan-3 alpha,-17 beta-diol by isotopic dilution mass spectrometry in plasma and prostatic tissue of patients affected by benign prostatic hyperplasia. Effects of 3month treatment with a GnRH analog. Author(s): Salerno R, Moneti G, Forti G, Magini A, Natali A, Saltutti C, Di Cello V, Costantini A, Serio M. Source: Journal of Andrology. 1988 July-August; 9(4): 234-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2460425

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Simultaneous radio-immunoassay measurement of testosterone (T) and dihydrotestosterone (DHT) without chromatography. Author(s): Delbeke D, Lejeune-Lenain C. Source: Annales De Biologie Clinique. 1982; 40(5): 579-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7158852

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Specific 5 alpha-dihydrotestosterone receptor and 5 alpha-reductase activity in human amniotic fluid cells. Author(s): Sultan C, Emberger JM, Devillier C, Chavis C, Terraza A, Descomps B, Jean R. Source: American Journal of Obstetrics and Gynecology. 1984 December 15; 150(8): 95660. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6507533

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Specific regulatory actions of dihydrotestosterone and estradiol on the dynamics of FSH secretion and clearance in humans. Author(s): Urban RJ, Dahl KD, Padmanabhan V, Beitins IZ, Veldhuis JD. Source: Journal of Andrology. 1991 January-February; 12(1): 27-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1901308

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Spermatic and peripheral venous plasma concentrations of testosterone, 17hydroxyprogesterone, androstenedione, dehydroepiandrosterone, delta 5-androstene3 beta,17 beta-diol, dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, 5 alpha-androstane-3 beta,17 beta-diol, and estradiol in boys with idiopathic varicocele in different stages of puberty. Author(s): Forti G, Toscano V, Casilli D, Maroder M, Balducci R, Adamo MV, Santoro S, Grisolia GA, Pampaloni A, Serio M. Source: The Journal of Clinical Endocrinology and Metabolism. 1985 August; 61(2): 3227. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3159746

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Spironolactone directly inhibits proliferation of cultured human facial sebocytes and acts antagonistically to testosterone and 5 alpha-dihydrotestosterone in vitro. Author(s): Akamatsu H, Zouboulis CC, Orfanos CE. Source: The Journal of Investigative Dermatology. 1993 May; 100(5): 660-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8491989

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Stimulation of aromatase activity by dihydrotestosterone in human skin fibroblasts. Author(s): Chabab A, Sultan C, Fenart O, Descomps B. Source: J Steroid Biochem. 1986 July; 25(1): 165-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2943941

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Stimulation of estradiol production from estrone-3-sulfate by 5 alphadihydrotestosterone in cultured human placental explants. Author(s): Ling WY, Wrixon WW, Acorn TP. Source: J Steroid Biochem. 1984 December; 21(6): 653-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6527534

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Studies on the treatment of idiopathic gynaecomastia with percutaneous dihydrotestosterone. Author(s): Kuhn JM, Roca R, Laudat MH, Rieu M, Luton JP, Bricaire H. Source: Clinical Endocrinology. 1983 October; 19(4): 513-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6354523

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Successful percutaneous dihydrotestosterone treatment of gynecomastia occurring during highly active antiretroviral therapy: four cases and a review of the literature. Author(s): Benveniste O, Simon A, Herson S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 September 15; 33(6): 891-3. Epub 2001 August 10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11512095

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Syntheses and ligand-binding studies of 1 alpha- and 17 alpha-aminoalkyl dihydrotestosterone derivatives to human sex hormone-binding globulin. Author(s): Hauptmann H, Metzger J, Schnitzbauer A, Cuilleron CY, Mappus E, Luppa PB. Source: Steroids. 2003 September; 68(7-8): 629-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957668

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Synthesis and evaluation of 7 alpha-iodo-5 alpha-dihydrotestosterone as a potential radioligand for androgen receptor. Author(s): Hoyte RM, Borderon K, Bryson K, Allen R, Hochberg RB, Brown TJ. Source: Journal of Medicinal Chemistry. 1994 April 15; 37(8): 1224-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8164266

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Synthesis of (5-azido-2-nitrobenzoyl)amido, (4-azido-2-nitrophenyl)amino, and (5azido-2-nitro-3,4, 6-trifluorophenyl)amino derivatives of 17alpha-methylamino-, 17alpha-ethylamino-, and 17alpha-propylamino-5alpha-dihydrotestosterone as reagents of different linker lengths for the photoaffinity labeling of sex hormone binding globulins and androgen receptors. Author(s): Mappus E, Chambon C, Fenet B, Rolland de Ravel M, Grenot C, Cuilleron CY. Source: Steroids. 2000 August; 65(8): 459-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10936617

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Testosterone and 5 alpha-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines. Author(s): Ortmann J, Prifti S, Bohlmann MK, Rehberger-Schneider S, Strowitzki T, Rabe T. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 April; 16(2): 113-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12012621

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Testosterone, 5 alpha-dihydrotestosterone and cortisol in men with and without alcohol-related aggression. Author(s): von der PB, Sarkola T, Seppa K, Eriksson CJ. Source: J Stud Alcohol. 2002 September; 63(5): 518-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12380846

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Testosterone, androstenedione and dihydrotestosterone concentrations are elevated in female patients with major depression. Author(s): Weber B, Lewicka S, Deuschle M, Colla M, Heuser I. Source: Psychoneuroendocrinology. 2000 November; 25(8): 765-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10996472

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The androgen control of sebum production. Studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity. Author(s): Imperato-McGinley J, Gautier T, Cai LQ, Yee B, Epstein J, Pochi P. Source: The Journal of Clinical Endocrinology and Metabolism. 1993 February; 76(2): 524-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8381804

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The effect of dihydrotestosterone and culture conditions on proliferation of the human prostatic cancer cell line LNCaP. Author(s): Chen HZ, Kirschenbaum A, Mandeli J, Hollander VP. Source: Steroids. 1992 June; 57(6): 269-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1440697

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The effect of dihydrotestosterone on transcription of prostatic acid phosphatase mRNA in human hyperplastic gland. Author(s): Dulinska J, Laidler P, Ostrowski WS, Mrozicki S, Galka M. Source: Acta Biochimica Polonica. 1997; 44(4): 751-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9584855

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The effect of finasteride, a 5 alpha-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness. Author(s): Dallob AL, Sadick NS, Unger W, Lipert S, Geissler LA, Gregoire SL, Nguyen HH, Moore EC, Tanaka WK. Source: The Journal of Clinical Endocrinology and Metabolism. 1994 September; 79(3): 703-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8077349

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The effects of dihydrotestosterone on the expression of p185(erbB-2) and c-erbB-2 mRNA in the prostatic cell line LNCaP. Author(s): Myers RB, Oelschlager DK, Hockett RD, Rogers MD, Conway-Myers BA, Grizzle WE. Source: The Journal of Steroid Biochemistry and Molecular Biology. 1996 December; 59(5-6): 441-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9010349

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The effects of testosterone and dihydrotestosterone on hypothalamic regulation of growth hormone secretion. Author(s): Eakman GD, Dallas JS, Ponder SW, Keenan BS. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 March; 81(3): 121723. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8772602

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The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study. Author(s): Kunelius P, Lukkarinen O, Hannuksela ML, Itkonen O, Tapanainen JS. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 April; 87(4): 146772. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11932266

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The expression of the ADAMs proteases in prostate cancer cell lines and their regulation by dihydrotestosterone. Author(s): McCulloch DR, Harvey M, Herington AC. Source: Molecular and Cellular Endocrinology. 2000 September 25; 167(1-2): 11-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11000516

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The first homozygous mutation (S226I) in the highly-conserved WSXWS-like motif of the GH receptor causing Laron syndrome: supression of GH secretion by GnRH analogue therapy not restored by dihydrotestosterone administration. Author(s): Jorge AA, Souza SC, Arnhold IJ, Mendonca BB. Source: Clinical Endocrinology. 2004 January; 60(1): 36-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678285

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The proliferative effects of 5-androstene-3 beta,17 beta-diol and 5 alphadihydrotestosterone on cell cycle analysis and cell proliferation in MCF7, T47D and MDAMB231 breast cancer cell lines. Author(s): Aspinall SR, Stamp S, Davison A, Shenton BK, Lennard TW. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2004 January; 88(1): 37-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15026082

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The regulation of prostate cancer cell adhesion to human bone marrow endothelial cell monolayers by androgen dihydrotestosterone and cytokines. Author(s): Cooper CR, Bhatia JK, Muenchen HJ, McLean L, Hayasaka S, Taylor J, Poncza PJ, Pienta KJ. Source: Clinical & Experimental Metastasis. 2002; 19(1): 25-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11918080

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The role of dihydrotestosterone in benign prostatic hyperplasia. Author(s): Carson C 3rd, Rittmaster R. Source: Urology. 2003 April; 61(4 Suppl 1): 2-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12657354

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The synthesis of 5-alpha-dihydrotestosterone from androgens by human gingival tissues and fibroblasts in culture in response to TGF-beta and PDGF. Author(s): Kasasa SC, Soory M. Source: Journal of Periodontal Research. 1996 July; 31(5): 313-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8858535

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Transdermal dihydrotestosterone therapy and its effects on patients with microphallus. Author(s): Choi SK, Han SW, Kim DH, de Lignieres B. Source: The Journal of Urology. 1993 August; 150(2 Pt 2): 657-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8326617

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Transdermal dihydrotestosterone treatment of 'andropause'. Author(s): de Lignieres B. Source: Annals of Medicine. 1993 June; 25(3): 235-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7687444

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Treatment with non-hypercalcemic analogs of 1,25-dihydroxyvitamin D3 increases responsiveness to 17beta-estradiol, dihydrotestosterone or raloxifene in primary human osteoblasts. Author(s): Katzburg S, Hendel D, Waisman A, Posner GH, Kaye AM, Somjen D. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2004 February; 88(2): 213-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15084353

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Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer. Author(s): Larson SM, Morris M, Gunther I, Beattie B, Humm JL, Akhurst TA, Finn RD, Erdi Y, Pentlow K, Dyke J, Squire O, Bornmann W, McCarthy T, Welch M, Scher H. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2004 March; 45(3): 366-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001675

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Ultrafiltrable plasma testosterone and 5 alpha-dihydrotestosterone as measured across the human testes. Author(s): Tamm J, Volkwein U, Becker H. Source: J Steroid Biochem. 1984 October; 21(4): 471-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6492805

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Unconjugated 5 alpha-androstan-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol in normal and pathological human seminal plasma. Comparison with testosterone, 5 alpha-dihydrotestosterone and testosterone-glucosiduronate. Author(s): Kurniawan E, Tamm J, Volkwein U, Schirren C. Source: Andrologia. 1983 March-April; 15(2): 141-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6859560

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CHAPTER 2. NUTRITION AND DIHYDROTESTOSTERONE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and dihydrotestosterone.

Finding Nutrition Studies on Dihydrotestosterone The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “dihydrotestosterone” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “dihydrotestosterone” (or a synonym): •

Crystalline dihydrotestosterone implants in the lateral septum of male rats. A positive effect on LH and FSH. Author(s): Department of Clinical Biochemistry, S. Cecilio University Hospital, Granada, Spain. Source: Roca, G Torres, J M Ruiz, E Ortega, E Endocr-Res. 2001 Feb-May; 27(1-2): 35-40 0743-5800

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Effects of delivering different amounts of dihydrotestosterone by ceramic implants on the reproductive system of male rats. Source: Benghuzzi, H A Barbaro, R M Bajpai, P K Biomed-Sci-Instrum. 1989; 25179-89 0067-8856

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Genistein and daidzein downregulate prostate androgen-regulated transcript-1 (PART-1) gene expression induced by dihydrotestosterone in human prostate LNCaP cancer cells. Author(s): Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Source: Yu, L Blackburn, G L Zhou, J R J-Nutr. 2003 February; 133(2): 389-92 0022-3166

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Lack of effect of testosterone and dihydrotestosterone compared to 17beta-oestradiol in 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine-mice. Author(s): Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL and Faculty of Pharmacy, Laval University, Quebec, Canada. Source: Ekue, A Boulanger, J F Morissette, M Di Paolo, T J-Neuroendocrinol. 2002 September; 14(9): 731-6 0953-8194

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Microinjection of dihydrotestosterone into the medial preoptic area produces malelike pattern of growth hormone secretion in ovariectomized female rats. Author(s): Department of Bioregulation, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan. Source: Tokita, Reiko Kasagi, Yoko Nakata, Tomoko Sakae, Kensaku Imaki, Toshihiro Minami, Shiro Neuroendocrinology. 2002 June; 75(6): 384-91 0028-3835

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Pathophysiological evaluation associated with sustained delivery of danazol and dihydrotestosterone in adult male rodents. Author(s): University of Mississippi Medical Center, Jackson 39216. Source: Benghuzzi, H A Bajpai, P K England, B G Biomed-Sci-Instrum. 1994; 30197-204 0067-8856

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Suppression of spermatogenesis by means of continuous delivery of danazol in combination with dihydrotestosterone from ALCAP drug delivery devices. Author(s): Department of Biology, University of Dayton, Ohio. Source: Benghuzzi, H A Bajpai, P K England, B G Biomed-Sci-Instrum. 1990; 26141-9 0067-8856

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Treatment of metastatic lipid cell tumor of the ovary with BV-CAP and VAC chemotherapy, using serum testosterone and dihydrotestosterone as tumor markers. Author(s): Department of Obstetrics and Gynecology, School of Medicine, Sunny, Stony Brook, N.Y. Source: Patsner, B Piver, M S Eur-J-Gynaecol-Oncol. 1988; 9(6): 441-4 0392-2936

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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMD®Health: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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The following is a specific Web list relating to dihydrotestosterone; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Minerals Zinc Source: Prima Communications, Inc.www.personalhealthzone.com

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CHAPTER

3.

ALTERNATIVE MEDICINE DIHYDROTESTOSTERONE

AND

Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to dihydrotestosterone. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to dihydrotestosterone and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “dihydrotestosterone” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to dihydrotestosterone: •

5 alpha-reductase-catalyzed conversion of testosterone to dihydrotestosterone is increased in prostatic adenocarcinoma cells: suppression by 15-lipoxygenase metabolites of gamma-linolenic and eicosapentaenoic acids. Author(s): Pham H, Ziboh VA. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 November; 82(4-5): 393-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589947

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A direct, low-temperature 1-H, 13-C, and 19-F nuclear magnetic resonance study of boron trifluoride complexes with stigmasterol, androstanolone, androsterone, testosterone, nortestosterone, androstenedione, and progesterone-1,2. Author(s): Fratiello A, Stover CS.

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Source: The Journal of Organic Chemistry. 1975 May 2; 40(9): 1244-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1133643 •

A male specific hepatic estrogen binding protein: characteristics and binding properties. Author(s): Rogerson BJ, Eagon PK. Source: Archives of Biochemistry and Biophysics. 1986 October; 250(1): 70-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3767382

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A randomized, double-blind, placebo-controlled trial to determine the effectiveness of botanically derived inhibitors of 5-alpha-reductase in the treatment of androgenetic alopecia. Author(s): Prager N, Bickett K, French N, Marcovici G. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 2002 April; 8(2): 143-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006122

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Activation of Rb and decline in androgen receptor protein precede retinoic acidinduced apoptosis in androgen-dependent LNCaP cells and their androgenindependent derivative. Author(s): Gao M, Ossowski L, Ferrari AC. Source: Journal of Cellular Physiology. 1999 June; 179(3): 336-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10228952

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An unusual sex steroid-binding protein in mature male rat liver cytosol. Author(s): Dickson RB, Aten RF, Eisenfeld AJ. Source: Endocrinology. 1978 November; 103(5): 1636-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=107020

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Analysis of the nutritional supplement 1AD, its metabolites, and related endogenous hormones in biological matrices using liquid chromatography-tandem mass spectrometry. Author(s): Reilly CA, Crouch DJ. Source: Journal of Analytical Toxicology. 2004 January-February; 28(1): 1-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14987417

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Androgen and taxol cause cell type-specific alterations of centrosome and DNA organization in androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cells. Author(s): Schatten H, Ripple M, Balczon R, Weindruch R, Chakrabarti A, Taylor M, Hueser CN.

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Source: Journal of Cellular Biochemistry. 2000 January; 76(3): 463-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10649443 •

Androgen and the blocking of radiation-induced sensitization to Fas-mediated apoptosis through c-jun induction in prostate cancer cells. Author(s): Shimada K, Nakamura M, Ishida E, Kishi M, Konishi N. Source: International Journal of Radiation Biology. 2003 June; 79(6): 451-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12963547

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Androgen binding proteins in cock's tissues: properties of ear lobe protein and determination of binding sites in head appendages and other tissues. Author(s): Dube JY, Tremblay RR. Source: Endocrinology. 1974 October; 95(4): 1105-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4369781

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Androgen receptor binding to nuclear matrix in vitro and its inhibition by 8S androgen receptor promoting factor. Author(s): Colvard DS, Wilson EM. Source: Biochemistry. 1984 July 17; 23(15): 3479-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6466649

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Androgen receptor in rat liver: hormonal and developmental regulation of the cytoplasmic receptor and its correlation with the androgen-dependent synthesis of alpha2u-globulin. Author(s): Roy AK, Milin BS, McMinn DM. Source: Biochimica Et Biophysica Acta. 1974 July 4; 354(2): 213-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4135309

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Androgen treatment protects mouse liver chromatin from cleavage by endogenous nucleases during aging. Androgen and nuclease activity. Author(s): Mukherjee S, Asaithambi A, Thakur MK. Source: Molecular Biology Reports. 1995-96; 22(1): 59-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8858574

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Androgens induce resistance to bcl-2-mediated apoptosis in LNCaP prostate cancer cells. Author(s): Berchem GJ, Bosseler M, Sugars LY, Voeller HJ, Zeitlin S, Gelmann EP. Source: Cancer Research. 1995 February 15; 55(4): 735-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7850782

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Anti-androgenic action by red clover-derived dietary isoflavones reduces nonmalignant prostate enlargement in aromatase knockout (ArKo) mice. Author(s): Jarred RA, McPherson SJ, Jones ME, Simpson ER, Risbridger GP.

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Source: The Prostate. 2003 June 15; 56(1): 54-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746847 •

Antiandrogenic natural Diels--Alder-type adducts from Brosimum rubescens. Author(s): Shirota O, Takizawa K, Sekita S, Satake M, Hirayama Y, Hakamata Y, Hayashi T, Yanagawa T. Source: Journal of Natural Products. 1997 October; 60(10): 997-1002. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9358642

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Antiandrogenic phenolic constituents from Dalbergia cochinchinensis. Author(s): Pathak V, Shirota O, Sekita S, Hirayama Y, Hakamata Y, Hayashi T, Yanagawa T, Satake M. Source: Phytochemistry. 1997 December; 46(7): 1219-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9423292

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Anti-reproductive and other medicinal effects of Tropaeolum tuberosum. Author(s): Johns T, Kitts WD, Newsome F, Towers GH. Source: Journal of Ethnopharmacology. 1982 March; 5(2): 149-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7057655

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Antitumor agents. 217. Curcumin analogues as novel androgen receptor antagonists with potential as anti-prostate cancer agents. Author(s): Ohtsu H, Xiao Z, Ishida J, Nagai M, Wang HK, Itokawa H, Su CY, Shih C, Chiang T, Chang E, Lee Y, Tsai MY, Chang C, Lee KH. Source: Journal of Medicinal Chemistry. 2002 November 7; 45(23): 5037-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12408714

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Bicalutamide functions as an androgen receptor antagonist by assembly of a transcriptionally inactive receptor. Author(s): Masiello D, Cheng S, Bubley GJ, Lu ML, Balk SP. Source: The Journal of Biological Chemistry. 2002 July 19; 277(29): 26321-6. Epub 2002 May 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12015321

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Binding of Permixon, a new treatment for prostatic benign hyperplasia, to the cytosolic androgen receptor in the rat prostate. Author(s): Carilla E, Briley M, Fauran F, Sultan C, Duvilliers C. Source: J Steroid Biochem. 1984 January; 20(1): 521-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6200701

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Biosynthesis of ecdysteroid hormones by crustacean Y-organs: conversion of cholesterol to 7-dehydrocholesterol is suppressed by a steroid 5 alpha-reductase

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inhibitor. Author(s): Spaziani E, Wang WL. Source: Molecular and Cellular Endocrinology. 1993 September; 95(1-2): 111-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8243800 •

BMP-6-induced osteogenic differentiation of mesenchymal cell lines is not modulated by sex steroids and resveratrol. Author(s): Gruber R, Graninger W, Bobacz K, Watzek G, Erlacher L. Source: Cytokine. 2003 August 21-September 7; 23(4-5): 133-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12967649

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Ceramic systems for long-term delivery of chemicals and biologicals. Author(s): Bajpai PK, Benghuzzi HA. Source: Journal of Biomedical Materials Research. 1988 December; 22(12): 1245-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3235459

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Comparison of 3 alpha-hydroxysteroid dehydrogenase activities in the microsomal fractions of hyperplastic, malignant and normal human prostatic tissues. Author(s): Hudson RW. Source: J Steroid Biochem. 1984 April; 20(4A): 829-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6200705

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Comparison of finasteride (Proscar) and Serenoa repens (Permixon) in the inhibition of 5-alpha reductase in healthy male volunteers. Author(s): Strauch G, Perles P, Vergult G, Gabriel M, Gibelin B, Cummings S, Malbecq W, Malice MP. Source: European Urology. 1994; 26(3): 247-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7805711

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Comparison of nuclear 5 alpha-reductase activities in the stromal and epithelial fractions of human prostatic tissue. Author(s): Hudson RW. Source: J Steroid Biochem. 1987 March; 26(3): 349-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2438480

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Comparison of reporter gene assay and immature rat uterotrophic assay of twentythree chemicals. Author(s): Yamasaki K, Takeyoshi M, Yakabe Y, Sawaki M, Imatanaka N, Takatsuki M. Source: Toxicology. 2002 January 15; 170(1-2): 21-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750080

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Competitive binding of xenobiotic oestrogens to rat alpha-fetoprotein and to sex steroid binding proteins in human and rainbow trout (Oncorhynchus mykiss)

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plasma. Author(s): Milligan SR, Khan O, Nash M. Source: General and Comparative Endocrinology. 1998 October; 112(1): 89-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9748407 •

Correlation of clinical, endocrine and molecular abnormalities with in vivo responses to high-dose testosterone in patients with partial androgen insensitivity syndrome. Author(s): Tincello DG, Saunders PT, Hodgins MB, Simpson NB, Edwards CR, Hargreaves TB, Wu FC. Source: Clinical Endocrinology. 1997 April; 46(4): 497-506. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9196614

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Corticosteroids and lung surfactant levels in adult male rats. Author(s): Eik-Nes KB, Marthinsen AB, Lofthus R, Haug E. Source: J Steroid Biochem. 1987; 27(4-6): 1035-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2826897

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Current treatment of BPH. Author(s): Roylance P, Gibelin B, Espie J. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 1995; 49(7-8): 332-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8562858

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Cytosolic and nuclear androgen receptor activity in the cancer of the larynx. Author(s): Marugo M, Cordone G, Fazzuoli L, Rocchetti O, Bernasconi D, Laviosa C, Bessarione D, Giordano G. Source: J Endocrinol Invest. 1987 October; 10(5): 465-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3429787

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Effect of Pygeum africanum tadenan on micturition and prostate growth of the rat secondary to coadministered treatment and post-treatment with dihydrotestosterone. Author(s): Yoshimura Y, Yamaguchi O, Bellamy F, Constantinou CE. Source: Urology. 2003 February; 61(2): 474-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12597984

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Functional evaluation of Tadenan on micturition and experimental prostate growth induced with exogenous dihydrotestosterone. Author(s): Choo MS, Bellamy F, Constantinou CE. Source: Urology. 2000 February; 55(2): 292-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10688098

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Genistein and daidzein downregulate prostate androgen-regulated transcript-1 (PART-1) gene expression induced by dihydrotestosterone in human prostate LNCaP

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cancer cells. Author(s): Yu L, Blackburn GL, Zhou JR. Source: The Journal of Nutrition. 2003 February; 133(2): 389-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12566472 •

Pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosterone enanthate in non-human primates. Author(s): Weinbauer GF, Jackwerth B, Yoon YD, Behre HM, Yeung CH, Nieschlag E. Source: Acta Endocrinol (Copenh). 1990 April; 122(4): 432-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2333732

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Testosterone, dihydrotestosterone, trenbolone acetate, and zeranol alter the synthesis of cortisol in bovine adrenocortical cells. Author(s): Isaacson WK, Jones SJ, Krueger RJ. Source: Journal of Animal Science. 1993 July; 71(7): 1771-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8394304

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Treatment of metastatic lipid cell tumor of the ovary with BV-CAP and VAC chemotherapy, using serum testosterone and dihydrotestosterone as tumor markers. Author(s): Patsner B, Piver MS. Source: Eur J Gynaecol Oncol. 1988; 9(6): 441-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2466668

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMD®Health: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to dihydrotestosterone; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Benign Prostatic Hyperplasia Source: Healthnotes, Inc.; www.healthnotes.com Benign Prostatic Hyperplasia Source: Integrative Medicine Communications; www.drkoop.com BPH Source: Integrative Medicine Communications; www.drkoop.com Male Infertility Source: Prima Communications, Inc.www.personalhealthzone.com Prostate Enlargement Source: Integrative Medicine Communications; www.drkoop.com

•

Herbs and Supplements Saw Palmetto Alternative names: Serenoa serrulata, Serenoa repens, Sabal serrulata Source: Healthnotes, Inc.; www.healthnotes.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON DIHYDROTESTOSTERONE Overview In this chapter, we will give you a bibliography on recent dissertations relating to dihydrotestosterone. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “dihydrotestosterone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on dihydrotestosterone, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Dihydrotestosterone ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to dihydrotestosterone. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

In vivo and in vitro metabolism of dihydrotestosterone and androstanediol in rats by Van Doorn, Edward John; PhD from Queen's University at Kingston (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK21170

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. PATENTS ON DIHYDROTESTOSTERONE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “dihydrotestosterone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on dihydrotestosterone, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Dihydrotestosterone By performing a patent search focusing on dihydrotestosterone, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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The following is an example of the type of information that you can expect to obtain from a patent search on dihydrotestosterone: •

Biological methods utilizing dihydrotestosterone heptanoate Inventor(s): Keenan; Bruce S. (3639 Tartan, Houston, TX 77025), Sparrow; James T. (12119 Atwell, Houston, TX 77035) Assignee(s): none reported Patent Number: 4,956,357 Date filed: March 28, 1986 Abstract: Disclosed is synthesized dihydrotestosterone heptanoate, its method of synthesis, and its method of use as an androgenic hormone of male gynecomastia, as a hormonal probe, as well as other applications. Excerpt(s): The invention relates to dihydrotestosterone heptanoate, compositions including that compound, and methods of use thereof. Breast enlargement (gynecomastia) in adolescent males is a common phenomenon. Several methods of treatment have been tried. Treatment with the androgenic hormone testosterone has actually caused increased breast size (H. E. Carlson, Gynecomastia, 303 New Eng J. Med. 795-799 (1980)), I.robably because testosterone is converted to the female sex hormone estradiol in vivo by the aromatase enzyme. In another study, treatment was attempted with an alcoholic solution of Dihydrotestosterone (DHT) applied to the skin. J. M. Kuhn, R. Roca, M. H. Landot, M. Riev, J. P. Luton, Bricase, Studies in the Treatment of Idiopathic Gynaecomastia With Percutaneous Dihydrotestosterone, 520 Clinical Endocrinology 19:513 (1983). While in a majority of patients this was successful and systemic absorption: of DHT was indicated by elevations in its plasma levels, in about 1/5 of the subjects absorption was poor and there was no benefit. Also, in another 1/3 of the subjects, breast regression was incomplete. Another disadvantage of this technique is that the solution must be applied three to four times daily to be effective. This is inconvenient and esthetically objectionable. Web site: http://www.delphion.com/details?pn=US04956357__

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Composition for inhibiting production of dihydrotestosterone to treat benign prostate hyperplasia Inventor(s): Ahmed; Aftab J. (Marina Del Rey, CA), Braswell; A. Glenn (Atlanta, GA) Assignee(s): Braswell; Glenn A. (Miami, FL) Patent Number: 6,264,996 Date filed: December 11, 1997 Abstract: A pharmaceutical composition containing a dihydrotestosterone blocker of a 5.alpha.-reductase active site binding peptide, Serenoa repens, or mixtures thereof, encapsulated within liposomes, and a pharmaceutically acceptable carrier is described. The composition is preferably orally administered in amounts effective to block production of excessive amounts of dihydrotestosterone (DHT) in prostatic tissue. By doing so, the composition is able to prevent and treat disorders of the prostate, including benign prostate hyperplasia.

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Excerpt(s): This invention relates to a composition containing compounds which inhibit the reduction of testosterone to dihydrotestosterone (DHT) in prostate tissue. The composition is used to prevent excessive levels of DHT in prostate tissue, a major contributing cause of benign prostate hyperplasia (BPH). Benign prostate hyperplasia (BPH) in mammals, particularly human males, is known to result from prolonged accumulation of testosterone in the prostate. The testosterone is converted in prostatic tissue to a more potent metabolite dihydrotestosterone (DHT). DHT stimulates cellular proliferation in the prostatic tissue, causing enlargement of the prostate. In the prostate, DHT has a "normal" base level in mammals in order to properly stimulate cellular proliferation within the prostate and to undertake other reported physiological roles. When the DHT levels exceed the base level, excessive cellular proliferation begins, accompanied by prostate enlargement. Web site: http://www.delphion.com/details?pn=US06264996__ •

Compositions and treatments for reducing potential unwanted side effects associated with long-term administration of androgenic testosterone precursors Inventor(s): Bucci; Luke R. (West Valley City, UT) Assignee(s): Weider Nutrition International, Inc (Salt Lake City, UT) Patent Number: 6,117,429 Date filed: August 11, 1998 Abstract: A method for reducing potential adverse effects of androgenic testosterone precursors by interfering with production or action of testosterone and estrogen metabolites by nutrient combinations is described. Although androgenic testosterone precursors themselves have little or no toxicity, there is the potential for their metabolites, estradiol and dihydrotestosterone, to enhance or cause hormoneresponsive illnesses such as breast or prostatic cancer, benign prostatic hyperplasia, or hirsutism or acne in women. The use of the invented nutrient combinations reduces the formation or action of estradiol and dihydrotestosterone, thereby reducing potential adverse effects from increased production of these hormones following androgenic testosterone precursor administration. This may be accomplished without negating the effects of testosterone on muscle anabolism. The nutrient combinations include androstenedione, DHEA, pregnenolone, androstenediols, norandrostenedione and norandrostenediols, and natural products which reduce estrogen effects in the estrogenresponsive tissues, and substances to reduce formation of dihydrotestosterone from testosterone in prostate tissue. Excerpt(s): The invention relates to the use of nutrient combinations to prevent or reduce potential adverse effects from administration of androgenic testosterone precursors to humans and other mammals Specifically, the invention relates to coadministration of androgenic testosterone precursors such as pregnenolone, androstenediols, norandrostenediols, norandrostenedione, androstenedione or dehydroepiandrosterone in combination with natural products which inhibit estrogen effects in liver, adipose, prostate, ovarian, uterine, breast and other estrogen-responsive tissues, and substances which inhibit the production of dihydrotestosterone in prostate tissue. Androstenedione (.DELTA.sup.4 -androstene-3,17-dione) is an adrenal steroid hormone. Pregnenolone is a precursor for dehydroepiandrosterone. Dehydroepiandrosterone (DHEA) is a precursor of androstenedione. Androstenedione is a direct precursor of estrone and testosterone in target tissues that possess the appropriate receptors and enzymes. Androstenediols are direct precursors for

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testosterone after oral administration in adult humans (unpublished data). 19Norandrostenedione is a precursor for 19-nortestosterone, which has anabolic actions similar to testosterone, with less androgenic actions. 19-Norandrostenedione is a potential precursor for estrone. Testosterone is important for the development and maintenance of male sexual organs and characteristics, behavioral effects, anabolic (growth-promoting) actions, and metabolic effects for all tissues, especially muscles, liver and kidney. (Kutsky, R. J., Handbook of Vitamins, Minerals and Hormones, 2.sup.nd ed., Van Nostrand Reinhold Company, New York, 1981). Estrogens are essential for the development and maintenance of female reproductive organs and characteristics, pregnancy, and metabolic effects for all tissues (Kutsky, 1981). Androstenedione levels in tissues, including skeletal muscle, of men and women decrease significantly with age. (Deslypere, J. P. and Vermeulen, A., Influence of age on steroid concentrations in skin and striated muscle in women and in cardiac muscle and lung tissue in men, J. Clin. Endocrinol. Metab. 61:648-653 (1985)). Since muscle wasting is associated with aging, these findings suggest that the loss of androstenedione is involved in muscle wasting. The corollary that androstenedione administration would maintain muscle mass is enticing, but has not been studied yet. Nevertheless, the data support an anabolic effect of androstenedione on muscle tissue in both men and women, with more effectiveness in men. Web site: http://www.delphion.com/details?pn=US06117429__ •

Dihydrotestosterone for use in androgenotherapy Inventor(s): De Lignieres; Bruno (Draveil, FR) Assignee(s): Laboratoires Besins Iscovesco (Paris, FR) Patent Number: 5,648,350 Date filed: July 8, 1996 Abstract: The present invention is directed to the administration of dihydrotestosterone (DHT) for preventing prostate cancer in male patients more than 50 years old and of reducing levels of plasma-borne sex hormone binding globulins (SHBG) in male patients having elevated levels thereof. Excerpt(s): The present invention relates to forms of administration of dihydrotestosterone, DHT for short, whose therapeutic uses are many, and in particular the forms adapted for androgenotherapy, particularly in persons in danger of prostate hyperplasia, in particular benign hyperplasia. It has been suggested until now that the use of DHT could result in risks for the prostate of subjects more than 50 years old. Prostate cancer and benign prostate hypertrophy, BPH for short, are disorders which depend in part on the androgens and it is easy to see that this type of risk is to be taken very seriously into consideration, particularly in the case of the treatment of andropause. From 60 years on, BPH, by comparison with the case of young adults, becomes a statistically normal condition in untreated subjects. The first period of prostate growth is connected to puberty and the testicular secretion of androgens, but hormonal influences during the second period of prostate growth after 50 years are until now far from being identified with precision. However, experience has shown that a second rapid increase of the testicular androgen secretion is quite excluded and that on the contrary, the plasma levels of the biologically available androgens tend to decrease after 50 years. Certain authors have proposed as a plausible explanation the accumulation of DHT in the prostate tissue, but this supposition has been discarded on

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the basis of more recent studies comparing prostate tissues of similar origins with or without BPH. Web site: http://www.delphion.com/details?pn=US05648350__ •

Method for preferential production of ratites of a desired sex Inventor(s): Crews; David (Austin, TX), Wibbels; Thane (Austin, TX) Assignee(s): Reproductive Sciences, Inc. (Austin, TX) Patent Number: 5,377,618 Date filed: July 31, 1992 Abstract: The present invention is a method for sex determination in ratites, such as ostriches. The method includes the steps of administering a material that causes sex to be determined to a fertilized ratite egg and incubating the egg until it hatches. Preferably, the administering step includes the step of injecting the material into the egg and preferably before the injecting step, there is the step of drilling a hole into the eggshell of the egg. The material that determines sex in ratites includes natural estrogens or a functionally equivalent amount of its synthetic mimics to cause female development and natural nonaromatizable androgens or a functionally equivalent amount of its synthetic mimics to cause male development. Preferably, the material is estradiol-17beta (for female development) or dihydrotestosterone (for male development). A solution may, for example, be comprised of 1.2 milligrams of estradiol17beta preferably dissolved in 40 microliters of 95% ethanol, or 7.5 milligrams of dihydrotestosterone preferably dissolved in 100 microliters of 95% ethanol, respectively. Excerpt(s): The present invention is related to hormone-induced sex determination of animals. More specifically, the present invention relates to the control of sex determination and sexual differentiation of ratite birds (e.g. ostrich, emu, rhea, kiwi, and cassowary) by the administration of specific sex determining substances to the egg before sexual differentiation of the embryonic gonads. The fundamental difference between the mechanisms underlying genotypic sex determination (GSD) and environmental sex determination lies in the trigger that initiates sex determination; in the former, gonadal sex is determined at fertilization by the pairing of sex chromosomes, whereas in the latter, gonadal sex is determined much later in embryogenesis as a consequence of the embryo's environment. They are alike, however, in that in both (i) the primary sex determiner operates as a trigger that initiates the cascade of events that shape sex differences, and (ii) hormones secreted by the embryonic gonad govern the subsequent differentiation and development of other components of sexuality (Crews and Bull, 1987; Wilson et al., 1981). A major variant of environmental sex determination is temperature-dependent sex determination (TSD). TSD was originally discovered in the African rainbow lizard (Agama agama) in 1966 by Madeline Charnier. Extensive research has revealed that in many oviparous reptiles, the temperature during the middle-third of embryogenesis is the critical cue determining the gonadal sex of the hatchling (Bull, 1980; Janzen and Paukstis, 1991). In TSD, sex determination operates as a switch mechanism that appears to be absolute; no individuals of ambiguous or intermediate sex are produced (Bull, 1985a and b, 1987a and b; Wibbels et al., 1991a). Because gonadal sex is determined after fertilization and egg-Laying in TSD, the primary sex ratio can be manipulated simply by varying incubation conditions. Web site: http://www.delphion.com/details?pn=US05377618__

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Ribozyme cleavage of 5.alpha.-reductase mRNA Inventor(s): Kashani-Sabet; Mohammed (San Francisco, CA), Scanlon; Kevin J. (Pasadena, CA) Assignee(s): City of Hope (Duarte, CA), The Regents of the University of California (Oakland, CA) Patent Number: 5,880,277 Date filed: July 16, 1997 Abstract: The steroid enzyme 5.alpha.-reductase is responsible for the conversion of testosterone to the more-potent androgen dihydrotestosterone (DHT). The catalytic cleavage of nucleic acid encoding 5.alpha.-reductase by a ribozyme which selectively recognizes such nucleic acid reduces the level of expression of 5.alpha.-reductase by mammalian cells including human cells treated with such ribozyme. The reduction of nucleic acid (e.g. mRNA) levels leads to a corresponding reduction of enzyme levels and dihydrotestosterone levels in surrounding tissues, thus providing a therapeutic effect. The transformation of 5.alpha.-reductase producing cells with an expression vector containing a structural gene for a ribozyme is shown to decrease 5.alpha.-reductase expression. Pharmaceutical compositions and methods useful for topically administering effective amounts of such a ribozyme to hair follicle cells also are exemplified. Excerpt(s): The present invention relates to the cleavage of mRNA directing the expression of the enzyme steroid 5.alpha.-reductase in mammalian cells, including human cells. More specifically, the present invention provides ribozymes capable of selectively cleaving such mRNA, thereby advantageously reducing the expression of 5.alpha.-reductase by cells exposed to such a ribozyme. The invention also provides methods and compositions for administering such ribozymes to cells, including methods and compositions for topically administering a 5.alpha.-reductase-mRNAspecific ribozyme to, inter alia, hair follicle cells for the treatment of androgenic alopecia. The microsomal enzyme steroid 5.alpha.-reductase (EC1.3.99.5) catalyzes the conversion of 4-ene-3-keto-steroids to the corresponding 5.alpha.-dihydro-3-keto steroids in human and other mammalian tissues. The conversion of testosterone to the more-potent androgen dihydrotestosterone ("DHT") is one of the best-characterized and best-known roles of this enzyme. DHT is considered to be the most potent androgen and to be responsible for differentiation of the male external genitalia and prostate as well as for virilization at puberty. See Labrie et al., Endocrinology 131:3, 1571-1573 (1992). Of the several organs that produce androgens, the testes produce these hormones in the greatest amounts. Centers in the brain exert primary control over the level of androgen production and, as described in greater detail below, numerous physical manifestations and disease states result when ineffective production control results in excessive androgen hormone production. Web site: http://www.delphion.com/details?pn=US05880277__

Patents 117

•

Use of 5alpha-androstanediol or dihydrotestosterone levels in humans

5alpha-androstanedione

to

increase

Inventor(s): Llewellyn; William Charles (P.O. Box 1162, Sound Beach, NY 11789) Assignee(s): none reported Patent Number: 6,242,436 Date filed: June 15, 2000 Abstract: This invention discloses a method of administering direct precursors of the hormone dihydrotestosterone as a means of increasing androgen levels in humans. As men age, a decline in androgenic hormone levels is typically noted, possibly resulting in muscle mass, bone density and energy loss. Various methods have therefore been developed to supplement androgens for men with declining levels. This invention teaches using precursors to testosterone, in that DHT and its precursors cannot be converted to estrogens in the human body. This may be a very advantageous trait for aging men at risk for benign prostatic hypertrophy, as estrogenic and androgenic action are both needed to induce this condition. As testosterone is the primary substrate for the synthesis of estradiol in men, its use as a target for androgen replacement may pose a greater health risk. Excerpt(s): This invention relates a method of administering the dihydrotestosterone precursor hormone 5alpha-androstanediol or 5alpha-androstanedione as a means of increasing dihydrotestosterone levels in humans. Although testosterone is considered to be the primary male androgen, in many sites of action it is actually dihydrotestosterone that is the active form of this steroid. Dihydrotestosterone (DHT) is a more potent form of testosterone, shown to be roughly three to four times more active in the human body in comparison. Its higher level of activity is attributed to the ability of this hormone to bind to the androgen receptor with greater affinity, and with more stability, than testosterone. The activity of DHT is most closely related to the development and maintenance of male sexual characteristics, including external virilization, sexual maturity at puberty, spermatogenesis, sexual behavior/libido and erectile functioning. DHT has also been shown to be equally effective as testosterone at inducing the expected benefits of androgen replacement on mood, sexual function, bone and muscle. A number of methods have been developed to restore androgen concentration in humans with declining levels. Several injectable esterified testosterone preparations have been fashioned that allow a slow release of hormone into the blood stream over the course of several days to weeks for example, however all provide inconsistent dosing as there is great variance in hormone release from the site of injection, such that a short supraphysiological rush may eventually be followed by days of subnormal hormone concentrations. The buildup of estrogens due to the natural process of aromatization may exaggerate the side effects to such medication, particularly at times when testosterone levels are abnormally high, as supraphysiological levels of estrogens in the male body have been linked to gynecomastia (female breast tissue development), water retention and edema, and increased fat deposition. More basically, recent studies have made clear that both androgens and estrogens play a synergistic role in the promotion of benign prostatic hypertrophy (BPH). This suggests that an aromatizable androgen such as testosterone may be less than ideal for use in older men at risk for such disease. Also a number of synthetic oral androgen derivatives have been developed including methyltestosterone, fluoxymesterone and stanozolol. All such compounds are alkylated at the 17.sup.th carbon position (alpha orientation), an alteration that inhibits reduction of the steroid to inactive 17-ketosteroid form. While this greatly improves oral bioavailability of the compound, this alteration has also been

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shown to place stress on the liver, in some instances resulting in organ damage. Although the use of a c-17 alpha alkylated oral androgen may prove much more comfortable for the patient in terms of dosing and control over blood hormone level compared to an injectable preparation, the possible risk of developing complications with liver functions may make them much less useful for androgen replacement compared to injectable preparations, particularly for extended periods of therapy. Web site: http://www.delphion.com/details?pn=US06242436__

Patent Applications on Dihydrotestosterone As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to dihydrotestosterone: •

Pharmaceutical composition in the form of a gel or a solution based on dihydrotestosterone, process for preparing it and uses thereof Inventor(s): Masini-Eteve, Valerie; (Verrieres Le Buisson, FR), Taravella, Brigitte; (Paris, FR) Correspondence: Piper Rudnick; P. O. Box 64807; Chicago; IL; 60664-0807; US Patent Application Number: 20030087885 Date filed: March 13, 2002 Abstract: The present invention relates to a pharmaceutical composition in the form of a gel or a solution and is characterized in that it contains dihydrotestosterone and also at least one penetration promoter, to processes for preparing it and to uses thereof. Excerpt(s): The present invention relates to a pharmaceutical composition in the form of a gel or a solution based on dihydrotestosterone (DHT). The invention also relates to processes for preparing these formulations, as well as to their uses. DHT is a metabolite of testosterone. In the sexual organs such as the prostate and the seminal vesicles, testosterone is reduced to DHT by an enzyme, 5-alpha reductase. During andropause (or "male menopause" or "partial deficiency of ageing male"), the secretion of androgens decreases and, in certain cases, this may entail pathological disorders. In particular, a change in protein synthesis and in the enzymatic activities of the target tissues is observed. Added to the anomalies of testosterone production and transportation, are anomalies of metabolism by the target tissues, these anomalies to a large extent remaining undetected in the plasmatic assays usually performed and which form the specificity of the hypogonadism of the ageing male. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with dihydrotestosterone, you can access the U.S. Patent Office archive via the Internet at the 9

This has been a common practice outside the United States prior to December 2000.

Patents 119

following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “dihydrotestosterone” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on dihydrotestosterone. You can also use this procedure to view pending patent applications concerning dihydrotestosterone. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

10

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

11

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “dihydrotestosterone” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 9670 150 9 4 46 9879

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “dihydrotestosterone” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

18 Adapted 19

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on dihydrotestosterone can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to dihydrotestosterone. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to dihydrotestosterone. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “dihydrotestosterone”:

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Hair Diseases and Hair Loss http://www.nlm.nih.gov/medlineplus/hairdiseasesandhairloss.html Infertility http://www.nlm.nih.gov/medlineplus/infertility.html Male Genital Disorders http://www.nlm.nih.gov/medlineplus/malegenitaldisorders.html Prostate Cancer http://www.nlm.nih.gov/medlineplus/prostatecancer.html Prostate Diseases http://www.nlm.nih.gov/medlineplus/prostatediseases.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on dihydrotestosterone. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

New Approach to Prostate Problems Source: Washington, DC: Physicians Committee for Responsible Medicine. 1998. 4 p. Contact: Available from Physicians Committee for Responsible Medicine. 5100 Wisconsin Avenue, NW, Suite 404, Washington, DC 20016. (202) 686-2210. Fax (202) 6862216. E-mail: [email protected]. Full text available at www.pcrm.org/health/Preventative_Medicine/prostate.html. PRICE: Single copy free. Summary: This fact sheet from the Physicians Committee for Responsible Medicine outlines the use of diet therapy for preventing and treating prostate problems, notably benign prostatic hyperplasia (BPH). The fact sheet first describes the anatomy and physiology of the prostate, noting that mild prostate symptoms sometimes improve with no treatment at all. However, men with difficulty urinating are advised to seek medical care in order to avoid kidney problems and continued discomfort. The fact sheet considers the drugs that are sometimes prescribed to relax the pressure in the prostate or to block the hormones that lead to enlargement (finasteride is in the latter category). The fact sheet also briefly reviews the traditional treatments for BPH, including transurethral resection of the prostate (TURP) surgery. The author then describes the role of the diet in creating and, possibly, in treating prostate problems. In the prostate cells, testosterone is turned into a powerful hormone called DHT

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(dihydrotestosterone), which drives prostate enlargement. Foods can strongly influence sex hormones, including testosterone. The author hypothesizes that eliminating meats and dairy products and adding more vegetables to the diet can turn down the hormonal stimulation of the prostate and prevent prostate problems. The remainder of the fact sheet discusses research that supports this hypothesis. One section focuses on the role of diet therapy in cancer, particularly prostatic cancer. A final section briefly reviews the use of prostate-specific antigen (PSA) levels to monitor prostatic disease activity. 21 references. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to dihydrotestosterone. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMD®Health: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to dihydrotestosterone. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with dihydrotestosterone. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about dihydrotestosterone. For more

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information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “dihydrotestosterone” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “dihydrotestosterone”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “dihydrotestosterone” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “dihydrotestosterone” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

21

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

22

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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DIHYDROTESTOSTERONE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 17-Hydroxyprogesterone: A hydroxyprogesterone with medical uses similar to that of progesterone. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Actin: Essential component of the cell skeleton. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH]

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Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [NIH]

Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Alcohol Dehydrogenase: An enzyme that catalyzes reversibly the final step of alcoholic fermentation by reducing an aldehyde to an alcohol. In the case of ethanol, acetaldehyde is reduced to ethanol in the presence of NADH and hydrogen. The enzyme is a zinc protein which acts on primary and secondary alcohols or hemiacetals. EC 1.1.1.1. [NIH] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU]

Dictionary 143

Alkaline: Having the reactions of an alkali. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allium: A genus of liliaceous herbs containing onions (Allium cepa), garlic (Allium sativum), and others; many produce pungent, often bacteriostatic and physiologically active compounds and are used as food, condiment, and medicament, the latter in traditional medicine. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino Acid Neurotransmitters: Amino acids released by neurons as intercellular messengers. Among the amino acid neurotransmitters are glutamate (glutamic acid) and GABA which are, respectively, the most common excitatory and inhibitory neurotransmitters in the central nervous system. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

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Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgen-Binding Protein: Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as sex hormone binding-globulin. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Androstanes: The family of steroids from which the androgens are derived. [NIH] Androstenediols: Unsaturated androstane derivatives which are substituted with two hydroxy groups in any position in the ring system. [NIH] Androstenedione: A steroid with androgenic properties that is produced in the testis, ovary, and adrenal cortex. It is a precursor to testosterone and other androgenic hormones. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anemic: Hypoxia due to reduction of the oxygen-carrying capacity of the blood as a result of a decrease in the total hemoglobin or an alteration of the hemoglobin constituents. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]

Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antiandrogens: Drugs used to block the production or interfere with the action of male sex

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hormones. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antidiabetic Agent: A substance that helps a person with diabetes control the level of glucose (sugar) in the blood so that the body works as it should. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH]

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Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its

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subdivisions is the basal (basement) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in

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a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Breast Neoplasms: Tumors or cancer of the breast. [NIH] Bulbar: Pertaining to a bulb; pertaining to or involving the medulla oblongata, as bulbar paralysis. [EU]

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Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Castration: Surgical removal or artificial destruction of gonads. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH]

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Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Centrioles: Self-replicating, short, fibrous, rod-shaped organelles. Each centriole is a short cylinder containing nine pairs of peripheral microtubules, arranged so as to form the wall of the cylinder. [NIH] Centrosome: The cell center, consisting of a pair of centrioles surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (mitotic spindle apparatus). [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chimera: An individual that contains cell populations derived from different zygotes. [NIH]

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Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Coitus: Sexual intercourse. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH]

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Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the

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formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Copulation: Sexual contact of a male with a receptive female usually followed by emission of sperm. Limited to non-human species. For humans use coitus. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH]

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Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin E: A 50-kD protein that complexes with cdk2 in the late G1 phase of the cell cycle. [NIH]

Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [NIH] Cyproterone Acetate: An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the

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hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands,

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hair follicles, and sebaceous glands. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Deuterium Oxide: The isotopic compound of hydrogen of mass 2 (deuterium) with oxygen. (From Grant & Hackh's Chemical Dictionary, 5th ed) It is used to study mechanisms and rates of chemical or nuclear reactions, as well as biological processes. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Diethylstilbestrol: DES. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a

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molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diurnal: Occurring during the day. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Duct: A tube through which body fluids pass. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU]

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Elastin: The protein that gives flexibility to tissues. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH] Emus: Members of the Casuariiformes, an order of flightless, running birds. The Emu is the only surviving member of the family Dromeidae. They naturally inhabit forests, open plains, and grasslands in Australia. [NIH] Enanthate: An oily injectable contraceptive given every 8 weeks. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes

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it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Factors: Events, characteristics, or other definable entities that have the potential to bring about a change in a health condition or other defined outcome. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epiphyseal: Pertaining to or of the nature of an epiphysis. [EU] Epitestosterone: 17 alpha-Hydroxy-androst-4-ene-3-one. A naturally occurring stereoisomer of testosterone with androgenic activity. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU]

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Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoiesis: The production of erythrocytes. [EU] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estriol: (16 alpha,17 beta)-Estra-1,3,5(10)-triene-3,16,17-triol. A metabolite of estradiol and usually the predominant estrogenic metabolite in urine. During pregnancy, large amounts of estriol are produced by the placenta. It has also been obtained from plant sources. The 16 beta-isomer has also been isolated from the urine of pregnant women. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Estrone: 3-Hydroxyestra-1,3,5(10)-trien-17-one. A metabolite of estradiol but possessing less biological activity. It is found in the urine of pregnant women and mares, in the human placenta, and in the urine of bulls and stallions. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), estrone may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excrete: To get rid of waste from the body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Facial: Of or pertaining to the face. [EU] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH]

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Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Finasteride: An orally active testosterone 5-alpha-reductase inhibitor. It is used as a surgical alternative for treatment of benign prostatic hyperplasia. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluoxymesterone: An anabolic steroid that has been used in the treatment of male hypogonadism, delayed puberty in males, and in the treatment of breast neoplasms in women. [NIH] Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Follicles: Shafts through which hair grows. [NIH] Follicular Atresia: The degeneration and resorption of an ovarian follicle before it reaches maturity and ruptures. [NIH] Forearm: The part between the elbow and the wrist. [NIH]

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Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids

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(steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropic: Stimulating the gonads; applied to hormones of the anterior pituitary which influence the gonads. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological

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therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gynaecomastia: Excessive development of the male mammary glands, even to the functional state. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Hantavirus: A genus of the family Bunyaviridae causing Hantavirus infections, first identified during the Korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. The genus has one recognized group (Hantaan group) consisting of several species including Dobrava-Belgrade virus, Seoul virus, Prospect Hill virus, Puumala virus, Thottapalayam virus, and Hantaan virus, the type species. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin C: A commonly occurring abnormal hemoglobin in which lysine replaces a glutamic acid residue at the sixth position of the beta chains. It results in reduced plasticity of erythrocytes. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU]

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Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]

Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH]

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Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxysteroid Dehydrogenases: Enzymes of the oxidoreductase class that catalyze the dehydrogenation of hydroxysteroids. (From Enzyme Nomenclature, 1992) EC 1.1.-. [NIH] Hydroxysteroids: Steroids in which one or more hydroxy groups have been substituted for hydrogen atoms either within the ring skeleton or on any of the side chains. [NIH] Hyperandrogenism: A state characterized or caused by an excessive secretion of androgens by the adrenal cortex, ovaries, or testes. The clinical significance in males is negligible, so the term is used most commonly with reference to the female. The common manifestations in women are hirsutism and virilism. It is often caused by ovarian disease (particularly the polycystic ovary syndrome) and by adrenal diseases (particularly adrenal gland hyperfunction). [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH]

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Hypophysis: A remnant of the entodermal pouch of Rathke beneath the mucous membrane of the pharynx, which shows pituitary tissue. [NIH] Hypospadias: A developmental anomaly in the male in which the urethra opens on the underside of the penis or on the perineum. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]

Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH]

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Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH]

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Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [NIH] Isoelectric Focusing: Electrophoresis in which a pH gradient is established in a gel medium and proteins migrate until they reach the site (or focus) at which the pH is equal to their isoelectric point. [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the

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dipolar ions are at a maximum. [NIH] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH]

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Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Levonorgestrel: A progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or

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cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]

Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair. It is detected when heterozygous markers for a locus appear monomorphic because one of the alleles was deleted. When this occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen,

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thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medroxyprogesterone Acetate: An injectable contraceptive, generally marketed under the name Depo-Provera. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the

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endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methyltestosterone: A synthetic hormone used for androgen replacement therapy and as an hormonal antineoplastic agent. [NIH] Micelles: Electrically charged colloidal particles or ions consisting of oriented molecules; aggregates of a number of molecules held loosely together by secondary bonds. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Micturition: The passage of urine; urination. [EU] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of

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the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic Spindle Apparatus: An organelle consisting of three components: (1) the astral microtubules, which form around each centrosome and extend to the periphery; (2) the polar microtubules which extend from one spindle pole to the equator; and (3) the kinetochore microtubules, which connect the centromeres of the various chromosomes to either centrosome. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism.

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Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motor Neurons: Neurons which activate muscle cells. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis,

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prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Nephropathy: Disease of the kidneys. [EU] Nerve Regeneration: Renewal or physiological repair of damaged nerve tissue. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurosurgical Procedures: Surgery performed on the nervous system or its parts. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP.

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Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Norgestrel: (+-)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one. A progestational agent with actions similar to those of progesterone. This racemic or (+-)-form has about half the potency of the levo form (levonorgestrel). Norgestrel is used as a contraceptive and ovulation inhibitor and for the control of menstrual disorders and endometriosis. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Matrix: The fibrogranular network of residual structural elements within which are immersed both chromatin and ribonucleoproteins. It extends throughout the nuclear interior from the nucleolus to the nuclear pore complexes along the nuclear periphery. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nucleates: Bacteria-inducing ice nucleation at warm temperatures (between zero and minus ten degrees C.). [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleic Acid Probes: Nucleic acid which complements a specific mRNA or DNA molecule, or fragment thereof; used for hybridization studies in order to identify microorganisms and for genetic studies. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Oestradiol: Growth hormone. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH]

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Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogenes: Genes which can potentially induce neoplastic transformation. They include genes for growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. When these genes are constitutively expressed after structural and/or regulatory changes, uncontrolled cell proliferation may result. Viral oncogenes have prefix "v-" before the gene symbol; cellular oncogenes (protooncogenes) have the prefix "c-" before the gene symbol. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Orchiectomy: The surgical removal of one or both testicles. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Ornithine Decarboxylase: A pyridoxal-phosphate protein, believed to be the rate-limiting compound in the biosynthesis of polyamines. It catalyzes the decarboxylation of ornithine to form putrescine, which is then linked to a propylamine moiety of decarboxylated Sadenosylmethionine to form spermidine. EC 4.1.1.17. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ostriches: Flightless birds of the order Struthioniformes which naturally inhabit open, low rainfall areas of Africa. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovariectomy: The surgical removal of one or both ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor

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molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Papilla: A small nipple-shaped elevation. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (=

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branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perineum: The area between the anus and the sex organs. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or

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glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH]

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Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Ploidy: The number of sets of chromosomes in a cell or an organism. For example, haploid means one set and diploid means two sets. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain

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conditions, as by stress. [EU] Pregnenolone: Steroid hormone. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoptic Area: Region of hypothalamus between the anterior commissure and optic chiasm. [NIH]

Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Proestrus: Phase of the estrous cycle preceding estrus during which the Graafian follicle undergoes maturation. Applies to animals. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prosencephalon: The part of the brain developed from the most rostral of the three primary vesicles of the embryonic neural tube and consisting of the diencephalon and telencephalon. [NIH]

Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostate-Specific Antigen: Kallikrein-like serine proteinase produced by epithelial cells of both benign and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. EC 3.4.21.77. [NIH]

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Prostatic acid phosphatase: PAP. An enzyme produced by the prostate. It may be found in increased amounts in men who have prostate cancer. [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible

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collection of pus within or beneath the epidermis). [EU] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Ratites: A grouping of flightless birds consisting of four orders: the Apterygiformes, which includes kiwis; the Casuariiformes, which includes emus; the Rheiformes, or rheas; and the Struthioniformes, or ostriches. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH]

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Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Paralysis: Complete or severe weakness of the muscles of respiration. This condition may be associated with motor neuron diseases; peripheral nerve disorders; neuromuscular junction diseases; spinal cord diseases; injury to the phrenic nerve; and other disorders. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU]

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Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Rheas: Members of the Rheiformes, a South American order of large, long-necked, longlegged, flightless birds, sometimes called American ostriches, though in a separate order from true ostriches. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrotum: In males, the external sac that contains the testicles. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU]

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Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sex Hormone-Binding Globulin: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Sex Ratio: The number of males per 100 females. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as

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the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin test: A test for an immune response to a compound by placing it on or under the skin. [NIH]

Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU]

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Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sperm Count: A count of sperm in the ejaculum, expressed as number per milliliter. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Stanozolol: Anabolic agent. [NIH] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stellate: Star shaped. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU]

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Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH]

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Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Terminalis: A groove on the lateral surface of the right atrium. [NIH] Testicle: The male gonad where, in adult life, spermatozoa develop; the testis. [NIH] Testicular: Pertaining to a testis. [EU] Testicular Feminization: A type of male pseudohermaphroditism in which the individual is phenotypically female, but with XY genotype. Fallopian tubes and a uterus may be present, but the gonads are usually testes. Androgens and estrogens are formed, but tissues are unresponsive to the androgens. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testolactone: An antineoplastic agent that is a derivative of progesterone and used to treat advanced breast cancer. [NIH]

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Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Topical: On the surface of the body. [NIH] Total androgen blockade: Therapy used to eliminate male sex hormones (androgens) in the body. This may be done with surgery, hormonal therapy, or a combination. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU]

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Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Translating: Conversion from one language to another language. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transurethral: Performed through the urethra. [EU] Transurethral resection: Surgery performed with a special instrument inserted through the urethra. Also called TUR. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Trenbolone: 17-beta-Hydroxyestra-4,9,11-trien-3-one. An anabolic steroid used mainly as a growth substance in animals. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH]

196

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Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]

Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. [NIH] Uridine Diphosphate Glucuronic Acid: A nucleoside diphosphate sugar which serves as a source of glucuronic acid for polysaccharide biosynthesis. It may also be epimerized to UDP iduronic acid, which donates iduronic acid to polysaccharides. In animals, UDP glucuronic acid is used for formation of many glucosiduronides with various aglycones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urodynamic: Measures of the bladder's ability to hold and release urine. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH]

Dictionary 197

Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Varicocele: A complex of dilated veins which surround the testicle, usually on the left side. [NIH]

Vas Deferens: The excretory duct of the testes that carries spermatozoa. It rises from the scrotum and joins the seminal vesicles to form the ejaculatory duct. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasectomy: An operation to cut or tie off the two tubes that carry sperm out of the testicles. [NIH]

Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venter: Belly. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virilism: Development of masculine traits in the female. [NIH] Virilization: The induction or development of male secondary sec characters, especially the induction of such changes in the female, including enlargement of the clitoris, growth of facial and body hair, development of a hairline typical of the male forehead, stimulation of secretion and proliferation of the sebaceous glands (often with acne), and deepening of the voice. Called also masculinization) [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH]

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Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral fat: One of the three compartments of abdominal fat. Retroperitoneal and subcutaneous are the other two compartments. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] War: Hostile conflict between organized groups of people. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zeranol: A non-steroidal estrogen analog. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

199

INDEX 1 17-Hydroxyprogesterone, 82, 91, 141 A Abdomen, 141, 148, 169, 172, 180, 181, 191, 192, 198 Abdominal, 32, 141, 180, 198 Abdominal fat, 141, 198 Aberrant, 39, 141 Ablation, 6, 35, 141 Acceptor, 141, 171, 179 Acetaldehyde, 23, 141, 142 Acetylcholine, 141, 177 Acid Phosphatase, 141 Acne, 30, 113, 141, 154, 197 Acne Vulgaris, 30, 141 Actin, 141, 176 Adaptability, 141, 150 Adenine, 85, 141 Adenocarcinoma, 71, 101, 141, 164 Adenosine, 21, 141, 182 Adipocytes, 141, 171 Adipose Tissue, 32, 63, 141, 142, 172 Adolescence, 38, 142, 181 Adrenal Cortex, 142, 144, 154, 160, 166, 184, 187 Adrenergic, 142, 157, 159, 193 Adverse Effect, 7, 32, 113, 142, 190 Afferent, 142, 171 Affinity, 16, 23, 86, 117, 142, 146, 190 Agar, 83, 142, 154, 167 Ageing, 51, 118, 142 Agenesis, 26, 142 Aggressiveness, 20, 142 Agonist, 9, 24, 59, 142, 157, 193 Alcohol Dehydrogenase, 23, 142 Aldehydes, 42, 142 Algorithms, 142, 147 Alimentary, 142, 180 Alkaline, 143, 149, 194 Alleles, 8, 143, 172 Allergen, 143, 189 Allium, 5, 143 Allogeneic, 66, 143 Alopecia, 30, 102, 116, 143 Alpha Particles, 143, 186 Alpha-fetoprotein, 105, 143, 161 Alternative medicine, 143 Amenorrhea, 143, 144, 183

Amino Acid Neurotransmitters, 24, 143 Amino Acid Sequence, 143, 144, 145, 162, 189 Amino Acids, 143, 144, 162, 181, 183, 185, 189, 196 Ammonia, 143, 193, 196 Amnion, 143 Amniotic Fluid, 90, 143 Amygdala, 24, 143, 171 Anabolic, 38, 44, 114, 144, 161, 191, 195 Anaesthesia, 144, 168 Analog, 6, 90, 144, 198 Analogous, 144, 195 Anatomical, 7, 33, 144, 151, 168, 174, 177 Androgen-Binding Protein, 144, 189 Androgenic, 7, 30, 35, 38, 103, 112, 113, 116, 117, 144, 155, 159 Androstanes, 16, 144 Androstenediols, 113, 144 Androstenedione, 51, 52, 53, 55, 63, 69, 74, 77, 78, 81, 84, 89, 91, 92, 101, 113, 144 Anemia, 144, 164 Anemic, 21, 144 Angiotensinogen, 144, 187 Animal model, 27, 33, 36, 144 Anions, 144, 169, 189 Anomalies, 118, 144 Anorexia, 38, 144 Anorexia Nervosa, 38, 144 Anovulation, 144, 183 Antiallergic, 144, 154 Antiandrogens, 9, 78, 144 Antibacterial, 145, 191 Antibiotic, 145, 191 Antibodies, 12, 18, 145, 164, 165, 167, 175, 182 Antibody, 40, 142, 145, 148, 152, 164, 165, 167, 168, 175, 186, 189, 191 Anticoagulant, 145, 185 Antidiabetic, 16, 145 Antidiabetic Agent, 16, 145 Antigen, 13, 35, 142, 145, 152, 165, 166, 167, 168, 174, 186, 189 Anti-inflammatory, 145, 154, 156, 163, 180 Anti-Inflammatory Agents, 145, 154 Antineoplastic, 145, 154, 174, 193 Antioxidant, 145, 180 Anuria, 145, 170

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Dihydrotestosterone

Anus, 145, 152, 181, 186 Aorta, 41, 145, 197 Apolipoproteins, 45, 145, 172 Apoptosis, 5, 6, 13, 26, 30, 40, 60, 85, 102, 103, 145 Aqueous, 146, 155, 158, 172 Arginine, 146, 165, 177, 179, 186 Aromatase, 14, 17, 35, 71, 91, 103, 112, 146 Arterial, 146, 151, 166, 185, 193 Arteries, 11, 145, 146, 148, 150, 153, 172, 176 Arteriolar, 146, 148, 187 Arterioles, 146, 148, 149 Artery, 11, 146, 154, 175, 176, 185, 187, 188 Aseptic, 146, 179, 191 Assay, 13, 27, 32, 37, 56, 86, 105, 146, 167, 186 Astrocytes, 8, 146, 174 Atrophy, 32, 146 Attenuated, 146, 156 Axons, 24, 146, 155 B Bacteria, 145, 146, 153, 159, 172, 174, 178, 189, 191, 195, 196 Bactericidal, 146, 160 Bacteriostatic, 143, 146 Bacterium, 146, 153 Base, 113, 141, 146, 155, 162, 170, 193 Basement Membrane, 146, 160 Bilateral, 147, 183 Bile, 147, 162, 163, 172, 192 Bilirubin, 147, 163 Binding Sites, 54, 103, 147 Bioavailability, 7, 15, 45, 64, 117, 147 Bioavailable, 15, 147 Biochemical, 3, 4, 10, 19, 21, 27, 54, 58, 143, 147, 170, 181 Biological therapy, 147, 164 Biomarkers, 32, 147 Biopsy, 147, 181 Biosynthesis, 42, 43, 85, 104, 147, 179, 189, 196 Biotechnology, 46, 48, 125, 147 Biotransformation, 17, 147 Bladder, 25, 41, 147, 168, 184, 196 Blood Cell Count, 147, 164 Blood Coagulation, 148, 149, 194 Blood Glucose, 148, 164, 169 Blood pressure, 11, 148, 149, 166, 175, 190 Blood vessel, 11, 148, 149, 150, 151, 153, 158, 162, 169, 173, 174, 190, 192, 194, 197 Blot, 13, 18, 33, 44, 45, 148, 167

Blotting, Western, 148, 167 Body Composition, 31, 35, 45, 148 Body Fluids, 147, 148, 157, 190, 196 Body Mass Index, 35, 148 Bone Density, 117, 148 Bone Marrow, 21, 28, 34, 94, 148, 167, 172, 175, 192 Boron, 32, 101, 148 Boron Neutron Capture Therapy, 148 Bowel, 148, 169, 171, 192 Bradykinin, 148, 177, 182 Breast Neoplasms, 148, 161 Bulbar, 22, 148 C Calcium, 12, 149, 152, 176, 180, 190, 194 Callus, 149, 158 Capillary, 148, 149, 172, 197 Carbohydrate, 149, 154, 163, 183 Carcinogen, 149, 160 Carcinogenesis, 6, 149 Carcinogenic, 149, 168, 184, 192, 196 Carcinoma, 26, 39, 42, 60, 67, 70, 71, 73, 75, 77, 87, 88, 149, 154 Cardiac, 18, 114, 149, 159, 176, 187, 192 Cardiovascular, 31, 32, 34, 149 Cardiovascular disease, 31, 32, 34, 149 Carrier Proteins, 149, 182, 186 Castration, 14, 24, 64, 65, 149 Catabolism, 23, 38, 149 Catecholamine, 149, 157 Catheterization, 11, 149, 169, 176 Caudal, 149, 167, 183 Cause of Death, 31, 46, 149 Cell Adhesion, 26, 62, 94, 149 Cell Communication, 25, 150 Cell Cycle, 5, 94, 150, 154 Cell Death, 6, 14, 145, 150, 177 Cell Differentiation, 150, 190 Cell Division, 146, 150, 155, 163, 169, 175, 182 Cell proliferation, 5, 14, 27, 40, 64, 73, 94, 150, 179, 190 Cell Survival, 150, 163 Central Nervous System, 7, 141, 143, 150, 162, 163, 174 Centrifugation, 150, 164, 174 Centrioles, 150 Centrosome, 102, 150, 175 Cerebral, 17, 150, 159, 160, 174, 193, 194 Cerebral Arteries, 150, 174 Cerebral hemispheres, 150, 193 Cerebrovascular, 18, 149, 150

201

Cerebrum, 150, 193 Cervix, 150, 187 Chemoprevention, 5, 150 Chemotherapy, 60, 98, 107, 150 Chimera, 46, 150 Chin, 151, 174 Cholesterol, 34, 104, 147, 151, 153, 157, 166, 172, 192, 193 Cholesterol Esters, 151, 172 Chondrocytes, 54, 151, 161 Chromatin, 21, 32, 103, 145, 151, 173, 178, 191 Chromosomal, 19, 20, 26, 151, 165, 188 Chromosome, 32, 76, 151, 153, 164, 171, 172, 188 Chronic, 7, 15, 19, 141, 151, 156, 159, 168, 170, 183, 192 Chronic renal, 151, 183 Chylomicrons, 151, 172 CIS, 27, 43, 151 Clamp, 18, 31, 151 Clear cell carcinoma, 151, 156 Clinical Medicine, 69, 151, 183 Clinical trial, 4, 7, 37, 125, 151, 157, 185, 186 Cloning, 19, 147, 151, 171 Cofactor, 43, 151, 185, 194 Cognition, 8, 151 Coitus, 151, 153 Colchicine, 151, 196 Collagen, 23, 146, 152, 161, 182, 184 Colloidal, 152, 158, 174, 189 Colon, 41, 54, 152, 170 Complement, 152, 162, 182, 189 Complementary and alternative medicine, 101, 108, 152 Complementary medicine, 101, 152 Computational Biology, 125, 152 Conception, 152, 153, 161, 191 Concomitant, 6, 153 Confounding, 45, 153 Conjugated, 153, 154, 188 Conjugation, 17, 147, 153 Connective Tissue, 148, 152, 153, 155, 162, 174, 192 Consciousness, 153, 157, 187 Constitutional, 4, 153 Constriction, 153, 169, 188 Continuous infusion, 45, 153 Contraception, 22, 49, 56, 153, 171 Contraceptive, 7, 153, 158, 173, 178 Contractility, 75, 153

Contraindications, ii, 153 Contralateral, 30, 153, 179 Copulation, 24, 153 Cornea, 153, 192 Coronary, 11, 149, 153, 154, 176 Coronary heart disease, 149, 153 Coronary Thrombosis, 154, 176 Corpus, 154, 172, 181, 184, 189, 194 Corpus Luteum, 154, 172, 184 Cortex, 150, 154, 159, 160, 175 Cortical, 50, 154, 160 Corticosteroid, 7, 154 Cortisol, 55, 92, 107, 154 Cortisone, 154, 156 Culture Media, 142, 154 Cutaneous, 34, 154, 171 Cyclic, 21, 150, 154, 164, 177 Cyclin, 5, 27, 154 Cyclin E, 27, 154 Cyproterone, 9, 75, 79, 88, 154, 161 Cyproterone Acetate, 9, 75, 79, 88, 154 Cytochrome, 17, 146, 154 Cytogenetics, 155, 188 Cytokine, 28, 105, 155 Cytoplasm, 145, 155, 163, 173, 175 Cytotoxic, 155, 190 D Dairy Products, 131, 155 Danazol, 57, 98, 155 Deamination, 155, 196 Decarboxylation, 155, 165, 179, 186 Dehydroepiandrosterone, 9, 52, 55, 59, 63, 74, 77, 78, 91, 113, 155 Deletion, 21, 145, 155, 172 Dendrites, 155, 177 Dendritic, 28, 155, 173 Dentate Gyrus, 155, 165 Deoxyribonucleic, 73, 155 Deoxyribonucleic acid, 73, 155 Deoxyribonucleotides, 155 Depolarization, 155, 190 Deprivation, 9, 155 Dermis, 155, 195 Detoxification, 156, 163 Deuterium, 43, 45, 156, 166 Deuterium Oxide, 45, 156 Dexamethasone, 66, 156 Diabetes Mellitus, 31, 156, 164 Diagnostic procedure, 111, 156 Dialyzer, 156, 164 Diastolic, 156, 166 Dietary Fats, 156, 171

202

Dihydrotestosterone

Diethylstilbestrol, 12, 156 Diffusion, 156, 167 Digestion, 142, 147, 148, 156, 169, 171, 172, 192 Dihydroxy, 18, 156 Dilution, 45, 84, 90, 156 Dimerization, 25, 156 Diploid, 156, 182, 183 Direct, iii, 9, 26, 27, 29, 32, 46, 63, 101, 113, 117, 150, 151, 156, 157, 187 Discrimination, 59, 156 Disease Progression, 67, 156 Disinfectant, 156, 160 Disposition, 7, 156 Dissociation, 63, 142, 156 Distal, 20, 33, 157, 185 Diurnal, 37, 157 Dopamine, 24, 157, 177 Dorsal, 14, 157, 183 Dorsum, 157 Dose-dependent, 12, 157 Double-blind, 35, 49, 102, 157 Drive, ii, vi, 76, 97, 157, 171 Duct, 25, 149, 157, 188, 197 Dyslipidemia, 34, 157 E Eating Disorders, 38, 157 Edema, 117, 157, 176 Efficacy, 3, 30, 157, 195 Ejaculation, 157, 189 Elastic, 157, 193 Elastin, 152, 158 Electrolyte, 154, 158, 170, 175, 190 Electrons, 145, 146, 158, 169, 173, 180, 186 Electrophoresis, 62, 83, 158, 167, 169 Elementary Particles, 158, 173, 177, 185 Embryo, 115, 143, 150, 158, 168 Embryogenesis, 115, 158 Emulsions, 142, 158 Emus, 158, 186 Enanthate, 57, 107, 158 Encapsulated, 112, 158, 172 Endocrine System, 158, 177 Endogenous, 27, 34, 64, 102, 103, 157, 158, 163, 185, 195 Endometriosis, 155, 158, 171, 178 Endometrium, 158, 174 Endothelial cell, 19, 28, 62, 94, 158, 161, 194 Endothelium, 158, 177 Endothelium-derived, 158, 177 Endotoxin, 159, 196

End-stage renal, 151, 159, 183 Energy balance, 159, 171 Entorhinal Cortex, 159, 165 Environmental Health, 124, 126, 159 Enzymatic, 67, 118, 149, 152, 159, 165 Epidemic, 31, 159 Epidemiologic Factors, 33, 159 Epidermal, 25, 26, 46, 59, 67, 72, 87, 159, 170, 173 Epidermal Growth Factor, 25, 59, 72, 87, 159 Epidermis, 155, 159, 170, 186 Epinephrine, 142, 157, 159, 177, 178, 196 Epiphyseal, 54, 159 Epitestosterone, 52, 159 Epithelial, 6, 14, 26, 40, 88, 105, 141, 159, 184 Epithelial Cells, 6, 26, 40, 159, 184 Epithelium, 40, 64, 146, 158, 159 Erectile, 24, 117, 159, 181 Erection, 159 Erythrocytes, 144, 147, 148, 160, 164, 189 Erythropoiesis, 21, 160 Estriol, 32, 74, 160 Estrogen receptor, 7, 12, 14, 15, 17, 29, 35, 46, 47, 160 Estrone, 32, 55, 64, 85, 87, 91, 113, 160 Ethanol, 23, 64, 115, 142, 160, 161 Ethnic Groups, 4, 20, 160 Eukaryotic Cells, 46, 160, 168, 196 Evoke, 160, 192 Excitatory, 143, 160, 163 Excrete, 145, 160, 170 Exogenous, 28, 29, 35, 106, 147, 158, 160, 163, 185 Extracellular, 66, 87, 146, 153, 160, 161, 174, 179, 190, 194 Extracellular Matrix, 66, 87, 153, 160, 161, 179 Extracellular Space, 160, 174 Extrapyramidal, 157, 160 F Facial, 88, 91, 160, 197 Fallopian tube, 160, 187, 193 Family Planning, 125, 160 Fat, 31, 32, 35, 44, 117, 141, 142, 148, 153, 154, 160, 171, 172, 188, 190, 193 Fatty acids, 64, 161 Fermentation, 142, 161 Fetoprotein, 161 Fetus, 77, 143, 161, 182, 184, 196 Fibroblast Growth Factor, 72, 161

203

Finasteride, 3, 29, 41, 49, 64, 69, 76, 93, 105, 130, 161 Fixation, 161, 189 Flatus, 161, 162 Fluorescence, 26, 43, 161 Fluoxymesterone, 45, 117, 161 Flutamide, 15, 29, 161 Fold, 6, 23, 161 Follicles, 161 Follicular Atresia, 75, 161 Forearm, 148, 161 Functional magnetic resonance imaging, 10, 162 G Gallbladder, 141, 162 Ganglia, 141, 162, 171, 177 Gas, 52, 143, 156, 161, 162, 166, 177, 178, 197 Gastric, 159, 162, 165 Gastrin, 162, 165 Gastrointestinal, 148, 159, 160, 162, 192, 196 Gastrointestinal tract, 160, 162, 196 Gene Expression, 12, 19, 21, 26, 35, 39, 40, 52, 68, 80, 87, 98, 106, 162 Generator, 37, 162 Genetic Code, 162, 178 Genetic Engineering, 147, 151, 162 Genetics, 10, 25, 55, 57, 68, 70, 88, 153, 155, 162 Genital, 25, 50, 52, 57, 60, 68, 70, 71, 72, 86, 130, 151, 162, 196 Genitourinary, 25, 162, 196 Genotype, 162, 181, 193 Germ Cells, 162, 179, 190, 191, 193 Gestation, 12, 162, 181, 182 Gland, 30, 93, 142, 154, 162, 166, 180, 182, 184, 188, 192, 194 Glomerular, 28, 162, 170 Glomerulus, 162 Glucocorticoid, 10, 36, 156, 162 Glucose, 27, 29, 31, 35, 65, 145, 148, 156, 163, 164, 169, 188 Glucose tolerance, 35, 163 Glucose Tolerance Test, 35, 163 Glucuronic Acid, 163, 196 Glucuronides, 86, 163 Glutamate, 24, 143, 163 Glutamic Acid, 143, 163, 164, 177, 184 Glycoprotein, 21, 81, 163, 189, 194, 196 Glycosidic, 163, 177, 178 Goats, 155, 163

Gonad, 28, 115, 163, 193 Gonadal, 11, 18, 29, 33, 37, 38, 69, 76, 115, 163, 192 Gonadotropic, 7, 163 Gonadotropin, 6, 22, 35, 37, 50, 52, 87, 163 Governing Board, 163, 183 Granulocytes, 163, 190, 198 Growth factors, 12, 14, 39, 40, 163, 174, 179 Guanylate Cyclase, 164, 177 Gynaecomastia, 91, 112, 164 H Hair follicles, 30, 156, 164 Hantavirus, 15, 164 Haploid, 164, 182, 183 Haptens, 142, 164, 186 Heart attack, 149, 164 Heartbeat, 164, 192 Hematocrit, 45, 148, 164 Hemodialysis, 44, 156, 164, 170 Hemoglobin, 45, 144, 148, 160, 164, 171 Hemoglobin C, 144, 164 Hemorrhage, 28, 164, 176, 192 Hepatic, 23, 35, 83, 102, 163, 164 Hepatocellular, 70, 83, 88, 164 Hepatocellular carcinoma, 70, 83, 88, 164 Heredity, 141, 162, 164 Heterogeneity, 70, 142, 165 Hippocampus, 8, 10, 155, 165, 171, 192 Hirsutism, 53, 82, 113, 154, 165, 166 Histamine, 165 Histidine, 84, 165 Histology, 29, 165, 180 Histones, 151, 165 Homodimer, 165, 195 Homogeneous, 26, 165 Homologous, 143, 165, 189, 193 Homozygotes, 85, 165 Hormonal, 7, 15, 22, 24, 28, 29, 31, 38, 46, 56, 70, 81, 103, 112, 114, 131, 146, 154, 165, 174, 194 Hormonal therapy, 46, 165, 194 Hormone therapy, 165 Human Development, 38, 124, 165 Hybrid, 26, 39, 165 Hybridization, 14, 165, 178 Hybridomas, 165, 169 Hydrogen, 141, 142, 146, 149, 156, 166, 171, 175, 177, 178, 179, 181, 185 Hydrolysis, 147, 166, 177, 181, 183 Hydrophobic, 166, 171 Hydroxylysine, 152, 166 Hydroxyproline, 152, 166

204

Dihydrotestosterone

Hydroxysteroid Dehydrogenases, 26, 166 Hydroxysteroids, 166 Hyperandrogenism, 37, 81, 166 Hypercholesterolemia, 157, 166 Hyperglycemia, 31, 166 Hyperlipidemia, 31, 157, 166 Hyperlipoproteinemia, 166, 172 Hyperplasia, 13, 14, 35, 47, 51, 82, 86, 104, 112, 113, 114, 166 Hypersensitivity, 143, 166, 189 Hypertension, 17, 31, 149, 166 Hyperthyroidism, 48, 78, 166 Hypertrichosis, 165, 166 Hypertriglyceridemia, 157, 166 Hypertrophy, 28, 44, 45, 47, 71, 72, 74, 75, 88, 114, 117, 147, 166 Hypogonadism, 45, 118, 161, 166 Hypophysis, 28, 167 Hypospadias, 50, 68, 167 Hypothalamic, 61, 66, 87, 93, 167 Hypothalamus, 78, 167, 171, 182, 184, 194 Hypoxemia, 28, 167 Hypoxia, 144, 167 I Idiopathic, 53, 81, 91, 112, 167 Immune response, 15, 28, 34, 145, 154, 164, 167, 189, 190, 192, 198 Immune system, 147, 167, 196, 198 Immunity, 34, 167 Immunization, 167, 184, 189 Immunoassay, 53, 90, 167 Immunoblotting, 29, 167 Immunodeficiency, 89, 167 Immunodiffusion, 142, 167 Immunoelectrophoresis, 142, 167 Immunogenic, 167, 186 Immunohistochemistry, 33, 40, 167 Immunologic, 167 Immunology, 142, 167 Immunosuppressive, 163, 167 Impairment, 168, 174 Impotence, 159, 168 In situ, 7, 13, 14, 28, 34, 40, 168 In Situ Hybridization, 7, 13, 34, 40, 168 In vitro, 4, 5, 26, 29, 35, 40, 41, 42, 44, 46, 58, 63, 67, 71, 78, 85, 87, 91, 92, 103, 109, 168, 194 In vivo, 11, 12, 20, 32, 34, 35, 40, 41, 42, 44, 71, 78, 106, 109, 112, 168, 174 Incision, 168, 169 Incontinence, 33, 168 Incubated, 5, 168

Incubation, 115, 168 Induction, 12, 29, 30, 34, 85, 103, 144, 168, 184, 197 Infarction, 168, 187 Infection, 15, 34, 146, 147, 164, 167, 168, 171, 172, 192, 198 Infertility, 108, 130, 168 Inflammation, 141, 145, 168, 183 Infusion, 168, 176 Ingestion, 163, 168, 194 Initiation, 15, 19, 25, 168, 195 Inotropic, 157, 168 Insight, 19, 25, 26, 43, 168 Insulin, 31, 34, 40, 45, 52, 63, 73, 163, 169, 188 Insulin-dependent diabetes mellitus, 169 Insulin-like, 40, 52, 73, 169 Interleukin-6, 72, 169 Internal Medicine, 34, 44, 158, 169 Interphase, 150, 169 Interstitial, 69, 160, 169 Intestinal, 163, 169 Intestine, 21, 148, 169, 170, 174 Intracellular, 18, 20, 24, 50, 74, 168, 169, 177, 190 Intramuscular, 50, 74, 169, 180 Intravenous, 7, 35, 168, 169, 180 Intrinsic, 14, 51, 74, 142, 146, 169 Intubation, 149, 169 Invasive, 18, 20, 167, 169, 173 Ion Channels, 18, 146, 169 Ions, 146, 157, 158, 166, 169, 170, 174 Ischemia, 17, 19, 146, 169, 176, 187 Isoelectric, 62, 169 Isoelectric Focusing, 62, 169 Isoelectric Point, 169 Isoflavones, 103, 170 K Kb, 124, 170 Keratin, 170, 188 Keratinocytes, 67, 170 Keto, 30, 43, 67, 116, 170 Kidney Disease, 29, 45, 124, 170 Kidney Failure, 29, 159, 170 Kidney Failure, Acute, 170 Kidney Failure, Chronic, 170 Kinetic, 26, 43, 170 L Labile, 10, 152, 170 Lactation, 170, 184 Large Intestine, 169, 170, 186, 187, 190 Larynx, 106, 170, 195

205

Latent, 20, 171, 183 Laxative, 142, 171 Leishmaniasis, 34, 171 Leptin, 63, 171 Lesion, 171, 172 Lethal, 12, 146, 171 Leucine, 45, 171 Levonorgestrel, 56, 171, 178 Libido, 7, 117, 144, 171 Ligament, 160, 171, 184 Ligands, 7, 16, 30, 36, 46, 171 Ligase, 46, 171 Limbic, 143, 171 Limbic System, 143, 171 Linkage, 20, 171 Lipase, 35, 171 Lipid, 35, 98, 107, 145, 158, 169, 170, 171, 172, 180 Lipid Peroxidation, 171, 180 Lipoprotein, 34, 45, 157, 171, 172 Lipoprotein Lipase, 35, 172 Liposomal, 30, 172 Liposome, 30, 172 Liver, 28, 43, 70, 79, 102, 103, 113, 118, 141, 143, 147, 162, 163, 164, 172, 174, 187, 196 Liver cancer, 143, 172 Lobe, 14, 103, 172 Localization, 23, 26, 53, 58, 60, 95, 167, 172 Localized, 9, 158, 161, 165, 166, 168, 172, 182 Loop, 43, 172 Loss of Heterozygosity, 20, 172 Low-density lipoprotein, 157, 172 Luciferase, 21, 172 Lutein Cells, 172, 184 Lymph, 158, 172, 173, 192 Lymphatic, 158, 168, 172, 174, 191 Lymphatic system, 172, 191 Lymphocytes, 145, 165, 167, 173, 191, 198 Lymphoid, 145, 173 M Magnetic Resonance Imaging, 35, 173 Magnetic Resonance Spectroscopy, 35, 173 Malformation, 26, 173 Malignant, 6, 38, 39, 40, 51, 62, 103, 105, 141, 145, 172, 173, 184 Malnutrition, 44, 146, 173, 176 Mammary, 73, 80, 164, 172, 173, 193 Maximum Tolerated Dose, 12, 173 Medial, 24, 78, 98, 173, 179 Mediate, 8, 26, 29, 38, 157, 173

Medicament, 143, 173 MEDLINE, 125, 173 Medroxyprogesterone Acetate, 49, 51, 173 Melanocytes, 173 Melanoma, 41, 148, 173 Memory, 8, 144, 173 Meninges, 150, 173 Menopause, 11, 18, 118, 173, 183 Menstrual Cycle, 15, 37, 173, 184 Menstruation, 143, 173, 174, 178 Mental, iv, 4, 8, 10, 38, 124, 126, 151, 156, 157, 173, 174, 184, 185, 188, 196 Mental Disorders, 8, 174, 184 Mental Health, iv, 4, 38, 124, 126, 174, 184 Mesenchymal, 26, 105, 159, 174 Mesolimbic, 24, 174 Metabolic Clearance Rate, 7, 48, 174 Metabolite, 5, 33, 67, 113, 118, 147, 160, 174 Metastasis, 94, 174 Metastatic, 27, 95, 98, 107, 174 Methyltestosterone, 117, 174 Micelles, 82, 174 Microbe, 174, 194 Microdialysis, 24, 174 Microglia, 146, 174 Microorganism, 151, 174, 180, 198 Microsomal, 42, 105, 116, 174 Micturition, 106, 174 Middle Cerebral Artery, 17, 174 Migration, 12, 175 Milliliter, 148, 175, 191 Mineralocorticoids, 142, 154, 175 Mitosis, 85, 145, 150, 175 Mitotic, 150, 175, 197 Mitotic Spindle Apparatus, 150, 175 Mobility, 49, 175 Modeling, 88, 175 Modification, 20, 23, 41, 162, 175, 186 Molecule, 46, 62, 145, 146, 147, 152, 154, 157, 158, 163, 166, 175, 178, 179, 180, 186, 190, 192, 197 Monitor, 39, 131, 175, 178 Monoclonal, 165, 167, 175 Monoclonal antibodies, 167, 175 Monocytes, 169, 175 Mononuclear, 175, 196 Monophosphate, 21, 175 Morphogenesis, 42, 175 Morphological, 21, 142, 158, 173, 176 Morphology, 7, 11, 13, 14, 32, 176 Motility, 32, 176

206

Dihydrotestosterone

Motor Neurons, 22, 176 Mucins, 176, 188 Mucocutaneous, 171, 176 Mucosa, 176, 184, 192 Muscle Fibers, 176 Muscular Atrophy, 22, 176 Myocardial infarction, 59, 154, 176 Myocardial Reperfusion, 176, 187 Myocardial Reperfusion Injury, 176, 187 Myocardium, 176 Myosin, 45, 176 N Narcotic, 141, 176 NCI, 1, 41, 123, 151, 176 Necrosis, 145, 168, 176, 177, 187 Neonatal, 21, 29, 177 Nephropathy, 28, 170, 177 Nerve Regeneration, 33, 177 Nervous System, 7, 38, 142, 150, 177, 192, 193 Networks, 40, 177 Neural, 12, 15, 25, 33, 38, 142, 161, 174, 177, 184 Neuraminidase, 21, 177 Neuroendocrine, 7, 16, 37, 177 Neuroendocrinology, 37, 98, 177 Neurologic, 8, 177 Neuronal, 12, 22, 177 Neurons, 8, 22, 24, 87, 143, 155, 160, 162, 176, 177, 193 Neurosurgical Procedures, 18, 177 Neurotransmitter, 141, 148, 150, 157, 163, 165, 169, 177, 178, 190, 192 Neutrons, 143, 148, 177, 186 Nitric Oxide, 24, 29, 80, 177 Nitrogen, 144, 161, 170, 178, 195 Norepinephrine, 142, 157, 177, 178 Norgestrel, 171, 178 Nuclear Matrix, 103, 178 Nuclear Pore, 178 Nucleates, 150, 178 Nuclei, 12, 44, 143, 153, 158, 162, 165, 171, 173, 175, 177, 178, 185 Nucleic acid, 40, 60, 116, 162, 165, 168, 178, 191 Nucleic Acid Hybridization, 165, 178 Nucleic Acid Probes, 40, 178 Nucleus, 12, 22, 145, 151, 154, 155, 156, 158, 160, 173, 175, 177, 178, 185, 192 O Oestradiol, 50, 51, 64, 65, 66, 71, 74, 78, 79, 80, 83, 88, 98, 178

Ointments, 178, 180 Oligomenorrhea, 178, 183 Oligosaccharides, 177, 178 Oliguria, 170, 179 Oncogenes, 6, 179 Optic Chiasm, 167, 179, 184 Orchiectomy, 18, 57, 179 Organ Culture, 72, 179, 194 Ornithine, 65, 179, 186 Ornithine Decarboxylase, 65, 179 Osmotic, 179, 189 Osteoblasts, 95, 179 Osteoporosis, 45, 179 Ostriches, 115, 179, 186, 188 Ovarian Follicle, 154, 161, 179 Ovariectomy, 18, 80, 179 Ovaries, 15, 146, 166, 179, 183, 187, 189 Ovary, 98, 107, 144, 154, 160, 163, 179, 192 Ovum, 154, 162, 179, 184, 198 Oxidation, 23, 42, 141, 145, 147, 154, 171, 179, 180 Oxidation-Reduction, 147, 180 Oxidative Stress, 29, 180 Oxygenation, 167, 180 P Palliative, 154, 180 Pancreas, 77, 141, 147, 169, 171, 180, 196 Pancreatic, 77, 89, 180 Pancreatic cancer, 89, 180 Papilla, 71, 80, 180 Paraffin, 13, 180 Paralysis, 148, 180 Parasite, 15, 180 Parathyroid, 65, 180, 194 Parathyroid Glands, 180 Parathyroid hormone, 65, 180 Parenteral, 21, 180 Particle, 172, 180, 195 Parturition, 180, 184 Patch, 180, 195 Pathogen, 168, 180 Pathologic, 19, 27, 145, 147, 153, 166, 180, 181, 187 Pathologic Processes, 145, 181 Patient Education, 130, 134, 136, 139, 181 Pediatrics, 25, 28, 31, 46, 181 Pelvic, 33, 158, 181, 184 Pelvis, 141, 179, 181, 196 Penis, 157, 167, 181, 187 Peptide, 36, 40, 60, 112, 161, 170, 171, 181, 183, 185 Perception, 12, 181

207

Percutaneous, 56, 65, 75, 81, 91, 112, 181 Perinatal, 7, 10, 181 Perineum, 167, 181 Peripheral blood, 13, 21, 181 Petroleum, 180, 181 PH, 3, 36, 40, 65, 69, 130, 148, 181 Pharmacodynamics, 107, 181 Pharmacokinetic, 7, 181 Pharmacologic, 7, 23, 181, 195 Pharynx, 167, 181 Phenotype, 7, 181 Phenyl, 98, 181 Phospholipases, 181, 190 Phospholipids, 160, 172, 182 Phosphorus, 149, 180, 182 Phosphorylation, 23, 182 Physical Fitness, 31, 182 Physiologic, 22, 44, 142, 147, 173, 174, 182, 186, 187 Physiology, 18, 36, 41, 102, 130, 158, 182 Pigment, 147, 173, 182 Pilot study, 13, 182 Pituitary Gland, 154, 161, 182 Placenta, 146, 160, 182, 184 Plants, 163, 176, 178, 182, 188, 195 Plasma, 21, 29, 45, 48, 50, 53, 55, 59, 62, 64, 65, 69, 76, 77, 78, 81, 82, 84, 85, 88, 89, 90, 91, 95, 96, 106, 112, 114, 145, 151, 163, 164, 166, 170, 175, 182, 187, 189 Plasma cells, 145, 182 Plasma protein, 182, 189 Platelet Activation, 182, 190 Platelet Aggregation, 177, 182 Platelets, 177, 182, 183 Ploidy, 72, 183 Pneumonia, 153, 183 Polycystic, 37, 166, 183 Polycystic Ovary Syndrome, 37, 166, 183 Polymerase, 90, 183 Polymorphic, 17, 151, 155, 183 Polymorphism, 85, 183 Polypeptide, 143, 152, 159, 165, 183, 184, 198 Polysaccharide, 145, 183, 196 Posterior, 157, 180, 183 Postmenopausal, 179, 183 Postnatal, 8, 12, 38, 183 Postsynaptic, 183, 190 Post-translational, 144, 183, 189 Potentiation, 183, 190 Practicability, 183, 195 Practice Guidelines, 126, 183

Preclinical, 27, 183 Precursor, 32, 52, 53, 58, 113, 117, 144, 157, 159, 178, 183, 191, 195, 196 Predisposition, 4, 183 Pregnenolone, 82, 113, 184 Prenatal, 7, 10, 158, 184 Preoptic Area, 24, 98, 184 Prevalence, 29, 184 Primary Prevention, 41, 184 Probe, 11, 112, 174, 184 Proestrus, 28, 184 Progeny, 153, 184 Progesterone, 11, 36, 37, 57, 59, 72, 73, 82, 84, 101, 141, 171, 178, 184, 192, 193 Progression, 3, 4, 9, 20, 27, 29, 144, 184 Progressive, 8, 95, 150, 151, 170, 177, 182, 184 Prolactin, 28, 55, 59, 66, 72, 184 Proline, 17, 152, 166, 184 Promoter, 20, 23, 39, 72, 118, 184 Prosencephalon, 184, 193 Prostate gland, 12, 184, 185 Prostate-Specific Antigen, 52, 87, 131, 184 Prostatic acid phosphatase, 93, 185 Prostatic Hyperplasia, 3, 6, 13, 14, 26, 40, 41, 47, 54, 59, 60, 65, 66, 67, 69, 79, 87, 90, 94, 108, 113, 130, 147, 161, 185 Protein Binding, 21, 185 Protein C, 39, 45, 46, 143, 145, 170, 171, 185, 196 Protein Kinases, 179, 185 Protein S, 43, 50, 88, 118, 147, 162, 185 Protocol, 13, 185 Protons, 143, 166, 173, 185, 186 Protozoa, 153, 171, 174, 185 Proximal, 20, 157, 185, 189 Psychic, 171, 174, 185 Puberty, 29, 31, 38, 52, 63, 91, 114, 116, 117, 161, 185 Public Policy, 125, 185 Publishing, 47, 185 Pulmonary, 61, 148, 170, 185, 193, 197 Pulmonary Artery, 148, 185, 197 Pulmonary Edema, 170, 185 Pulse, 37, 175, 185 Pustular, 141, 185 Putrescine, 179, 186, 191 Pyridoxal, 179, 186 Q Quality of Life, 44, 49, 186 R Race, 171, 175, 178, 186

208

Dihydrotestosterone

Racemic, 171, 178, 186 Radiation, 26, 103, 158, 161, 186, 198 Radioactive, 166, 175, 178, 186, 196 Radioimmunoassay, 50, 53, 84, 85, 186 Radiological, 181, 186 Radiopharmaceutical, 162, 186 Randomized, 35, 41, 49, 60, 94, 102, 157, 186 Randomized clinical trial, 41, 49, 186 Ratites, 115, 186 Reagent, 172, 186 Recombinant, 22, 26, 42, 43, 69, 186, 197 Recombination, 153, 186 Rectal, 25, 186 Rectum, 26, 145, 152, 161, 162, 168, 170, 184, 186, 187 Recurrence, 150, 187 Refer, 1, 152, 161, 172, 177, 187, 189 Refraction, 187, 191 Refractory, 9, 46, 187 Regeneration, 33, 161, 187 Regimen, 45, 157, 187 Relapse, 57, 187 Renin, 29, 144, 187 Renin-Angiotensin System, 29, 187 Reperfusion, 18, 176, 187 Reperfusion Injury, 18, 187 Reproductive system, 32, 98, 184, 187 Resection, 187 Resorption, 161, 187 Respiration, 175, 187 Respiratory Paralysis, 141, 187 Resuscitation, 28, 187 Retinoid, 16, 42, 188 Retinol, 42, 188 Retrospective, 41, 188 Rheas, 186, 188 Ribonuclease, 27, 188 Ribonucleoproteins, 178, 188 Ribose, 141, 188 Risk factor, 17, 31, 32, 41, 188 Rod, 146, 150, 151, 188 Rosiglitazone, 86, 188 S Saliva, 70, 174, 188 Salivary, 81, 180, 188, 192 Salivary glands, 188 Saponins, 188, 192 Satellite, 44, 188 Schizophrenia, 24, 38, 188 Screening, 20, 151, 188 Scrotum, 188, 197

Sebaceous, 30, 58, 156, 188, 197 Sebaceous gland, 30, 58, 156, 188, 197 Sebum, 79, 93, 141, 188 Sedimentation, 150, 188, 196 Selective estrogen receptor modulator, 189, 193 Semen, 62, 79, 157, 184, 189 Seminal vesicles, 6, 12, 118, 189, 197 Seminiferous tubule, 69, 75, 78, 144, 189, 191 Senile, 179, 189 Sensitization, 103, 189 Sepsis, 28, 189 Septal, 171, 189 Septum, 98, 189 Septum Pellucidum, 189 Serine, 184, 189 Serologic, 167, 189 Serum Albumin, 83, 186, 189 Sex Characteristics, 142, 144, 185, 189, 194 Sex Determination, 115, 189 Sex Hormone-Binding Globulin, 54, 73, 74, 76, 92, 189 Sex Ratio, 115, 189 Shock, 189, 195 Side effect, 24, 30, 113, 117, 142, 147, 189, 194 Signal Transduction, 5, 190 Signs and Symptoms, 45, 187, 190 Skeletal, 44, 45, 114, 144, 151, 190 Skeleton, 141, 166, 190 Skin test, 93, 190 Skull, 190, 193 Small intestine, 151, 165, 169, 190, 197 Smooth muscle, 41, 165, 187, 190, 192 Social Behavior, 38, 190 Social Environment, 186, 190 Sodium, 45, 175, 190, 193 Soft tissue, 148, 190 Solvent, 43, 160, 179, 190 Soma, 190 Somatic, 4, 142, 158, 171, 175, 190, 191 Somatic cells, 175, 191 Somatic mutations, 4, 191 Specialist, 132, 191 Species, 15, 21, 34, 49, 143, 151, 153, 159, 161, 164, 165, 171, 175, 180, 186, 190, 191, 192, 197, 198 Specificity, 16, 23, 35, 43, 118, 142, 191 Spectrum, 29, 174, 191 Sperm, 32, 65, 144, 151, 153, 189, 191, 196, 197

209

Sperm Count, 32, 65, 191 Spermatogenesis, 6, 22, 98, 117, 191 Spermatozoa, 189, 191, 193, 197 Spermidine, 179, 191 Sphincter, 170, 191 Spinal cord, 146, 150, 151, 173, 177, 187, 191 Spinous, 159, 170, 191 Spleen, 28, 172, 191 Stanozolol, 63, 117, 191 Steady state, 26, 191 Steel, 151, 191 Stellate, 23, 191 Sterile, 146, 180, 191 Sterility, 32, 50, 53, 57, 76, 79, 168, 191 Stimulus, 45, 153, 157, 169, 192, 194 Stomach, 141, 162, 163, 165, 181, 190, 191, 192 Stool, 152, 168, 170, 192 Strand, 183, 192 Stress, 29, 33, 41, 118, 149, 154, 180, 184, 192 Stroke, 17, 124, 149, 192 Stroma, 64, 192 Stromal, 14, 26, 105, 158, 192 Stromal Cells, 26, 192 Subacute, 168, 192 Subclinical, 168, 192 Subcutaneous, 35, 56, 141, 157, 180, 192, 198 Subiculum, 165, 192 Submaxillary, 159, 192 Subspecies, 191, 192 Substance P, 174, 188, 192 Substrate, 7, 42, 43, 46, 117, 177, 192 Substrate Specificity, 42, 192 Sudden cardiac death, 18, 192 Superoxide, 29, 192 Supplementation, 6, 45, 56, 192 Suppression, 6, 9, 21, 98, 101, 154, 192, 193 Suppressive, 21, 193 Surfactant, 25, 61, 106, 193 Survival Rate, 28, 193 Sweat, 155, 174, 193 Sympathomimetic, 157, 159, 178, 193 Symphysis, 151, 184, 193 Synaptic, 177, 190, 193 Synergistic, 76, 117, 184, 193 Systemic, 112, 145, 148, 159, 168, 193 Systolic, 166, 193 T Tamoxifen, 15, 65, 66, 70, 189, 193

Telencephalon, 11, 184, 193 Temporal, 7, 14, 18, 143, 165, 193 Temporal Lobe, 143, 193 Terminalis, 193, 194 Testicle, 163, 193, 197 Testicular, 9, 14, 22, 32, 50, 54, 55, 56, 58, 61, 65, 69, 71, 77, 114, 146, 193 Testicular Feminization, 54, 56, 69, 71, 193 Testis, 22, 51, 69, 144, 160, 193 Testolactone, 70, 193 Tetany, 180, 194 Thigh, 45, 194 Third Ventricle, 167, 194 Threshold, 11, 32, 166, 194 Thrombin, 182, 185, 194 Thrombomodulin, 185, 194 Thrombosis, 185, 192, 194 Thyroid, 73, 166, 180, 194, 196 Thyroid Gland, 166, 180, 194 Thyroxine, 73, 194 Tissue, 6, 14, 17, 19, 35, 38, 40, 41, 42, 46, 48, 50, 53, 55, 57, 58, 59, 65, 72, 73, 79, 80, 87, 88, 90, 105, 112, 113, 114, 117, 141, 142, 145, 146, 147, 148, 149, 153, 157, 158, 159, 161, 163, 166, 167, 169, 171, 173, 174, 176, 177, 181, 182, 183, 184, 187, 190, 192, 193, 194, 198 Tissue Culture, 59, 194 Tolerance, 141, 163, 194 Tomography, 9, 148, 173, 194 Topical, 30, 76, 160, 180, 194 Total androgen blockade, 65, 194 Toxic, iv, 30, 153, 167, 186, 194, 195 Toxicity, 7, 32, 113, 173, 194 Toxicology, 32, 69, 88, 102, 105, 126, 195 Toxins, 145, 163, 168, 175, 195 Trace element, 148, 195 Trachea, 170, 181, 194, 195 Traction, 151, 195 Transcription Factors, 20, 33, 179, 195 Transdermal, 45, 49, 56, 76, 94, 95, 195 Transduction, 6, 190, 195 Transfection, 21, 23, 39, 40, 147, 195 Transforming Growth Factor beta, 25, 195 Translating, 41, 195 Translocation, 22, 78, 195 Transmitter, 141, 146, 157, 169, 178, 195 Transurethral, 130, 195 Transurethral resection, 130, 195 Trauma, 28, 177, 195 Treatment Outcome, 13, 195 Trenbolone, 107, 195

210

Dihydrotestosterone

Trophic, 5, 195 Tryptophan, 152, 195 Tubulin, 34, 196 Tumor marker, 98, 107, 147, 196 Tumor Necrosis Factor, 59, 196 Tumor suppressor gene, 172, 196 Tumorigenic, 6, 196 Tyrosine, 157, 196 U Ubiquitin, 46, 196 Urea, 71, 170, 179, 193, 196 Uremia, 170, 196 Urethra, 26, 147, 167, 181, 184, 195, 196 Uridine Diphosphate, 163, 196 Uridine Diphosphate Glucuronic Acid, 163, 196 Urinary, 33, 41, 74, 86, 162, 168, 179, 196 Urine, 32, 33, 78, 145, 147, 159, 160, 163, 168, 170, 174, 179, 196 Urodynamic, 34, 196 Urogenital, 12, 19, 40, 162, 196 Uterus, 26, 150, 154, 158, 174, 179, 184, 187, 193, 196 V Vaccine, 185, 196 Vagina, 26, 41, 150, 156, 174, 187, 196, 197 Vaginal, 25, 33, 197 Varicocele, 91, 197 Vas Deferens, 53, 197 Vascular, 62, 155, 158, 168, 177, 179, 182, 194, 197 Vasectomy, 63, 86, 197 Vasodilator, 11, 148, 157, 165, 176, 197 VE, 38, 197 Vector, 23, 60, 116, 195, 197 Vein, 169, 178, 188, 197 Venous, 69, 91, 148, 185, 197

Venter, 197 Ventral, 14, 167, 197 Ventricle, 143, 165, 185, 193, 194, 197 Ventricular, 18, 176, 197 Venules, 148, 149, 197 Vesicular, 174, 197 Veterinary Medicine, 125, 197 Villi, 85, 87, 197 Vinblastine, 196, 197 Vincristine, 196, 197 Viral, 179, 195, 196, 197 Virilism, 166, 197 Virilization, 116, 117, 197 Virulence, 146, 194, 197 Virus, 89, 162, 164, 195, 197, 198 Viscera, 190, 198 Visceral, 32, 34, 171, 198 Visceral fat, 34, 198 Vitro, 26, 29, 32, 40, 41, 44, 46, 75, 198 Vivo, 12, 33, 34, 40, 41, 44, 198 W War, 164, 198 White blood cell, 145, 168, 172, 173, 182, 198 Windpipe, 181, 194, 198 Womb, 187, 196, 198 Wound Healing, 161, 198 X Xenograft, 36, 144, 198 X-ray, 35, 43, 148, 161, 178, 198 Y Yeasts, 181, 198 Z Zeranol, 107, 198 Zygote, 153, 198 Zymogen, 185, 198

211

212

Dihydrotestosterone

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