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  • Print publication year: 2013
  • Online publication date: February 2015

32 - Androgens and the androgen receptor (AR)

from Part 2.3 - Molecular pathways underlying carcinogenesis: nuclear receptors
    • By Nicole L. Moore, Dame Roma Mitchell Cancer Research Laboratories, Adelaide University/Hanson Institute, Adelaide, South Australia, Margaret M. Centenera, Dame Roma Mitchell Cancer Research Laboratories, Adelaide University/Hanson Institute, Adelaide, South Australia, Lisa M. Butler, Dame Roma Mitchell Cancer Research Laboratories, Adelaide University/Hanson Institute, Adelaide, South Australia, Theresa E. Hickey, Dame Roma Mitchell Cancer Research Laboratories, Adelaide University/Hanson Institute, Adelaide, South Australia, Wayne D. Tilley, Dame Roma Mitchell Cancer Research Laboratories, Adelaide University/Hanson Institute, Adelaide, South Australia
  • Edited by Edward P. Gelmann, Columbia University, New York, Charles L. Sawyers, Memorial Sloan-Kettering Cancer Center, New York, Frank J. Rauscher, III
  • Publisher: Cambridge University Press
  • DOI: https://doi.org/10.1017/CBO9781139046947.033
  • pp 378-391

Summary

Introduction

Androgens are sex steroid hormones that are produced in both males and females, albeit in different amounts. Androgens are essential for development and maintenance of the male phenotype (1), and are also important in females, where they can either act directly via the androgen receptor (AR) or indirectly as metabolic precursors for estrogen biosynthesis (2). The majority of circulating androgens in males and females are produced by the gonads, under hypothalamic–pituitary regulation, and adrenal glands. The major circulating androgens are dehydroepiandrosterone, DHEA sulfate, androstenedione, and testosterone, which can all be metabolized to other androgens or to estrogens. Testosterone and its intracrine metabolite, 5α-dihydrotestosterone (DHT), are the most potent androgenic hormones, as they bind with high affinity to the AR. Many organs in both males and females are sensitive to androgen action and, depending on the tissue-specific context, androgens regulate multiple cellular processes, including proliferation, differentiation, apoptosis, metabolism, secretory responses, and the synthesis of lipids and fatty acids (3). Accordingly, deregulation of AR expression and/or function is associated with a diverse range of clinical conditions, including androgen insensitivity syndrome (AIS), a form of motor neuron disease known as Kennedy's disease, male and female pattern baldness, hirsutism, acne, male infertility, polycystic ovary syndrome, benign prostatic hyperplasia, and breast and prostate cancer. In particular, the AR is considered an oncogene in the prostate as it plays a critical role at all stages of prostate carcinogenesis, and consequently, inhibition or abrogation of androgen signaling is the goal of hormonal therapies for this disease. In contrast, androgens predominantly have a growth inhibitory role in the breast, consistent with an emerging view of the AR playing a tumor-suppressive role in breast tumorigenesis.

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