Androgens and Androgen Receptor

Author: Chawnshang Chang

Publisher: Springer Science & Business Media

ISBN: 9781461511618

Category: Medical

Page: 503

View: 511

Androgen Receptors is the most comprehensive and up to date volume on the topic, including discussions of the basic mechanisms of androgen-androgen receptor actions, their roles in the androgen-related diseases, and their potential clinical applications. Key topics covered include: -The discovery and cloning of the androgen receptor; -Androgen receptor coregulators; -Androgen related genes and their consensus DNA response elements; -Basic mechanism of action including functional analyses, cellular localization and phosphorylation studies; -Cross-talk to other signal transduction systems; -The recent connections of androgens to women's diseases, such as osteoporosis and ovarian cancer. This book is of interest to students, basic scientists, and clinicians as both a study guide and reference of research in the androgen field. It could also be used as an advanced level text in endocrinology, urology, OBGYN, or oncology.
Investigating the Role of Testosterone Signaling at Androgen Receptors in Resiliency to Social Stress

Author: Catherine Tucker Clinard


ISBN: OCLC:973497396

Category: Androgens

Page: 144

View: 880

Social experience can alter how individuals cope with stressful events and contribute to individual differences in stress vulnerability. We have previously tested dominant and subordinate male Syrian hamsters (Mesocricetus auratus) in a conditioned defeat model and found that dominant individuals show reduced defeat-induced changes in behavior compared to subordinates. Dominant hamsters also show increased neural activation following social defeat stress in brain regions that regulate social behavior and coping with stress, including the medial amygdala (MeA). Because winning aggressive encounters generates a surge in plasma testosterone and androgen receptors are abundant in the MeA, we tested whether testosterone signaling at androgen receptors in the MeA contributes to the reduced effects of social defeat stress in dominant hamsters. Our overarching hypothesis was that dominant hamsters experience daily surges in plasma testosterone during the maintenance of their social status that increase the expression of androgen receptors in the MeA, which are necessary for their reduced conditioned defeat response compared to subordinates. We found that dominant hamsters experience a significant rise in plasma testosterone 15-min following an aggressive encounter compared to their pre-encounter baseline, whereas subordinates and control animals showed no change in testosterone. Furthermore, we investigated whether changes in androgen receptor and estrogen alpha-receptor immunoreactivity occur during the maintenance of dominance relationships. We paired male hamsters in daily agonistic encounters for 14 days to establish and maintain dominant/subordinate relationships. Dominant hamsters showed significantly more cells expressing androgen receptor immunoreactivity, but not estrogen alpha-receptor immunoreactivity, in the dorsal MeA (dMeA) and ventral lateral septum (vLS), compared to subordinates and controls. Also, blockade of androgen receptors with flutamide during the maintenance of dominance relationships increased the conditioned defeat response in dominant animals compared to vehicle-treated counterparts. Flutamide-treated dominant animals also showed reduced androgen receptor immunoreactivity in the dMeA, but not the vLS, compared to vehicle-treated dominants. Altogether, these results suggest that the maintenance of dominant social status generates neural plasticity that is associated with an upregulation of androgen receptors in the dMeA, and that activation of androgen receptors is necessary for resistance to conditioned defeat.
The Mechanism of Action of Androgens

Author: W.I.P. Mainwaring

Publisher: Springer Science & Business Media

ISBN: 9783642884290

Category: Medical

Page: 180

View: 156

My introduction to androgens was neither auspicious nor impressive. I was sitting my viva voce examination for a degree in physiology and had haltingly intimated to my examiner (name decorously withheld) that I intended to pursue a career in re search. "On what topic?" was the reply. I had been deeply impressed by the work of C. Huggins and C. V. Hodges (Cancer Res. 1, 293, 1941) on the dramatic arrest of canine prostatic hyperplasia by the administration of stilboestrol. With some en thusiasm, I responded, "On steroid hormones, because I am struck by the profound effects that may be achieved by relatively small numbers of molecules. " The examiner sank into deep contemplation before replying, "Young man, have you considered go ing into teaching?" Suitably chastened, I finally began my research career investigating the effects of steroids on the nucleic acid metabolism of experimental tumours and on the process cells. Reaching an impasse in this work, I mentioned one of senescence in animal day to Dr. G. F. Marrian that, somewhat surprisingly, we had no understanding of the fundamental mechanism of action of steroid hormones, especially the androgens. me to tackle this problem, particularly since exciting new insights He encouraged were then being made into the interaction of radioactively labelled oestradiol-l?,8 with such tissues as rat uterus.
Androgens and Androgen Receptor Signalling in Men

Author: Eleanor Frances Need


ISBN: OCLC:318175736

Category: Androgens

Page: 542

View: 139

Androgens are critical for the development and maintenance of adult male characteristics such as muscle mass and sexual function. Consequently, the established decline with age of serum testosterone (T) in males has major health implications. While the androgen receptor (AR) is the major mediator of genomic androgen action and is required for the development of the male phenotype, reproductive organs and the maintenance of male secondary sexual characteristics, it is the entrance of androgens into the cell that mediates the activation of the AR and the subsequent modulation of expression of androgen regulated genes. The objectives of this thesis were to develop a specific mammalian cell based bioassay capable of reliable measuring T in serum and to determine the ability of this bioassay to measure a physiologically relevant fraction of T in serum. Additionally, this thesis aimed to determine the relative contributions and roles of the activation functions of the AR to overall AR transcriptional activity along with the functional consequences for AR signalling of prostate cancer mutations which have previously been identified in the AF5 region of the AR NTD. The investigation of the roles of the activation functions in the AR in this thesis have revealed that while the AF1 domain is responsible for the majority of the transactivation activity of the AR, AF5 and AF2 govern the sensitivity and cellular response of the AR to androgens by providing protein and interdomain interaction interfaces. Furthermore, the evidence in this thesis demonstrates that the AR requires interdomain communication for sensitive AR signalling. Finally, the findings in this thesis demonstrate that the AF5 surface is required for the N/C interaction and coregulator interactions while advanced prostate cancer mutations identified within this region confer increased transactivation activity of the AR in the presence of high cellular levels of coregulators. Collectively, the findings in this thesis provide several novel insights into the mechanism of action of serum androgens and challenges several long held assumptions of androgenic action in males. These findings also delineate a mechanism of treatment failure in advanced prostate cancer, provide a novel model for the events leading to sensitive AR transactivation and contribute to the understanding of physiologically relevant levels of serum T.
Pharmacology, Biology, and Clinical Applications of Androgens

Author: Chuck Kelly

Publisher: John Wiley & Sons

ISBN: 0471133205

Category: Medical

Page: 552

View: 861

Pharmacology, Biology, and Clinical Applications of AndrogensCurrent Status and Future Prospects Edited by Shalender Bhasin, Henry L. Gabelnick, Jeffrey M. Spieler,Ronald S. Swerdloff, Christina Wang, and Chuck Kelly As agents that affect the male primary and accessory sex organs,androgens--particularly the hormones testosterone andandrosterone--play a critical role in the development,functionality, and overall health of the male reproductive system.However, since androgens also have far-ranging effects onmetabolism, neurological activity, and behavior, scientistsexploring the contraceptive or therapeutic potential of androgensneed reliable, up-to-date information on the complex biologicalactivities of these agents. Pharmacology, Biology, and Clinical Applications of Androgens:Current Status and Future Prospects presents contributions fromleading investigators around the world, offering a focused,state-of-the-art summary of the central issues and controversies inandrogen research. The book is arranged into sections coveringandrogen physiology, androgens and the prostate, and theneurobehavioral and metabolic effects of androgens--as well astheir role in disease therapy and male contraception, and thevarious delivery systems for each application. Every chapter in thetext provides an expert opinion on a cutting-edge topic in thefield while highlighting the key points of dissent and disagreementwithin the scientific community. This approach is intended tofoster a deeper understanding of the status of androgen researchand lay the groundwork for future investigations in eacharea. This book explores such current topics as: * Androgen regulation of Sertoli cell function * Testosterone and spermatogenesis * Androgen effects on benign prostatic hyperplasia (BPH) andprostate cancer * Androgen effects on cognitive processes, sexual function, andaggressive behavior * Contraceptive efficacy of hormonal suppression of spermatogenesis * The latest transdermal and implantation delivery systems forandrogens Offering multifaceted coverage of the field, Pharmacology, Biology,and Clinical Applications of Androgens is an indispensable aid toall basic scientists and clinical investigators interested in thebiological actions of either natural or synthetic androgens.
Androgen Receptors

Author: Silvia Socorro

Publisher: Nova Science Pub Incorporated

ISBN: 1629486930

Category: Science

Page: 173

View: 109

The androgen receptor (AR) mediates a wide range of physiological actions of androgens in cells and tissues. Contributions to this volume cover distinct topics of AR signalling, extending from the structural aspects of AR to its role in androgen-associated diseases and potential clinical applications. Some key issues covered include an overview of structural aspects of AR genes and proteins in mammalian and non-mammalian vertebrate species and a description of the identified AR splice variants in pathological and non-pathological conditions. The structural and functional analysis of coding and untranslated regions of AR are discussed in the context of diseases such as androgen insensitivity syndrome, spinal and bulbar muscular atrophy, polycystic ovarian syndrome and breast, ovary and prostate cancers. The role of AR regulated genes implicated in prostate cancer progression is also explored. This book is a comprehensive conceptual review of the recent findings on AR genes and protein structure, molecular variants, ligands, target genes and signalling mechanisms. Graduate students, scientists and professionals can use it as both a study text and a reference for research purposes.
Androgens in Health and Disease

Author: Carrie Bagatell

Publisher: Springer Science & Business Media

ISBN: 9781592593880

Category: Medical

Page: 448

View: 377

Authoritative researchers and clinicians review our latest understanding of andrology in both basic science and clinical medicine. Topics range from explaining the biology of androgens-from several different perspectives-to illuminating their role in the development and modulation of physiologic systems. Authors demonstrate in a number of cases that testosterone can be a useful adjunct to the treatment of a variety of disease states. Other chapters consider important topics such as androgens use in athletes, the potential of androgens to improve physical function and quality of life in older men, and androgens as potential male contraceptives.