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Estrogen and androgen signaling in the pathogenesis of BPH

Abstract

Estrogens and androgens have both been implicated as causes of benign prostatic hyperplasia (BPH). Although epidemiological data on an association between serum androgen concentrations and BPH are inconsistent, it is generally accepted that androgens play a permissive role in BPH pathogenesis. In clinical practice, inhibitors of 5α-reductase (which converts testosterone to the more potent androgen dihydrotestosterone) have proven effective in the management of BPH, confirming an essential role for androgens in BPH pathophysiology. To date, multiple lines of evidence support a role for estrogens in BPH pathogenesis. Studies of the two estrogen receptor (ER) subtypes have shed light on their differential functions in the human prostate; ERα and ERβ have proliferative and antiproliferative effects on prostate cells, respectively. Effects of estrogens on the prostate are associated with multiple mechanisms including apoptosis, aromatase expression and paracrine regulation via prostaglandin E2. Selective estrogen receptor modulators or other agents that can influence intraprostatic estrogen levels might conceivably be potential therapeutic targets for the treatment of BPH.

Key Points

  • Androgens play a permissive role in the pathogenesis of benign prostatic hyperplasia (BPH)

  • Inhibition of 5α-reductase activity is currently the mainstay of hormonal treatment of BPH

  • Increasing evidence from epidemiological, animal and in vitro studies supports a role for estrogens in the pathogenesis of BPH

  • Estrogen receptors ERα and ERβ mediate proliferative and antiproliferative effects of estrogens on prostate cells, respectively

  • Some androgens are weak ligands for ERs but might have potent agonistic effects on prostate cells because of high tissue concentrations

  • The prevalence of ERα and ERβ in hyperplastic prostate raises the potential of selective estrogen receptor modulators as potential therapeutic agents for BPH

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Figure 1: Biosynthesis and metabolism of the major androgens and estrogens in human prostate.
Figure 2: Schematic representation of human ARs and ERs.
Figure 3: Actions of ER subtypes in the major prostate cell types.

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C. K. M. Ho and F. K. Habib contributed equally to researching data, discussing content, writing and editing of the manuscript.

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Ho, C., Habib, F. Estrogen and androgen signaling in the pathogenesis of BPH. Nat Rev Urol 8, 29–41 (2011). https://doi.org/10.1038/nrurol.2010.207

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