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Androgens and androgen receptor (AR) signaling are necessary for prostate development and homeostasis. AR signaling also drives the growth of nearly all prostate cancer cells. The role of androgens and AR signaling has been well characterized in metastatic prostate cancer, where it has been shown that prostate cancer cells are exquisitely adept at maintaining functional AR signaling to drive cancer growth. As androgens and AR signaling are so intimately involved in prostate development and the proliferation of advanced prostate cancer, it stands to reason that androgens and AR are also involved in prostate cancer initiation and the early stages of cancer growth, yet little is known of this process. In this review, we summarize the current state of knowledge concerning the role of androgens and AR signaling in prostate tissue, from development to metastatic, castration-resistant prostate cancer, and use that information to suggest potential roles for androgens and AR in prostate cancer initiation., (© 2015 Society for Endocrinology.)

Introduction: Androgens regulate a wide array of physiological processes, including male sexual development, bone and muscle growth, and behavior and cognition. Because androgens play a vital role in so many tissues, changes in androgen signaling are associated with a plethora of diseases. How such varied responses are achieved by a single stimulus is not well understood. Androgens act primarily through the androgen receptor (AR), a hormone nuclear receptor that is expressed in a select variety of tissues., Methods: In order to gain a better understanding of how the tissue-selective effects of androgens are achieved, we performed a comparison of microarray data, using previously published datasets and several of our own microarray datasets. These datasets were derived from clinically relevant, AR-expressing tissues dissected from rodents treated with the full androgen dihydrotestosterone (DHT)., Results: We found that there is a diverse response to DHT, with very little overlap of androgen regulated genes in each tissue. Gene ontology analyses also indicated that, while several tissues regulate similar biological processes in response to DHT, most androgen regulated processes are specific to one or a few tissues. Thus, it appears that the disparate physiological effects mediated by androgens begin with widely varying effects on gene expression in different androgen-sensitive tissues., Conclusion: The analysis completed in this study will lead to an improved understanding of how androgens mediate diverse, tissue-specific processes and better ways to assess the tissue-selective effects of AR modulators during drug development.

Androgens and androgen receptor (AR) signaling are necessary for prostate development and homeostasis. AR signaling also drives the growth of nearly all prostate cancer cells. The role of androgens and AR signaling has been well characterized in metastatic prostate cancer, where it has been shown that prostate cancer cells are exquisitely adept at maintaining functional AR signaling to drive cancer growth. As androgens and AR signaling are so intimately involved in prostate development and the proliferation of advanced prostate cancer, it stands to reason that androgens and AR are also involved in prostate cancer initiation and the early stages of cancer growth, yet little is known of this process. In this review, we summarize the current state of knowledge concerning the role of androgens and AR signaling in prostate tissue, from development to metastatic, castration-resistant prostate cancer, and use that information to suggest potential roles for androgens and AR in prostate cancer initiation. [ABSTRACT FROM AUTHOR]