Androgenic to estrogenic switch in human adult prostate gland is regulated by epigenetic silencing of steroid 5α-reductase 2

Abstract

Benign prostatic hyperplasia (BPH) is the most common proliferative abnormality of the prostate. While all men experience some prostate growth as they age, the rate of growth varies among individuals. Steroid 5α-reductase 2 (SRD5A2) is a critical enzyme for prostatic development and growth. Previous work indicates that one-third of adult prostate samples do not express SRD5A2, secondary to epigenetic modifications. Here we show that estradiol is dramatically elevated, concomitant with significantly upregulated estrogen response genes, in prostate samples that are methylated at the SRD5A2 promoter. The phosphorylation of estrogen receptor α (ERα) in prostate stroma is upregulated when SRD5A2 expression is absent. We show that TNF-α suppresses SRD5A2 mRNA and protein expression, and simultaneously promotes expression of aromatase, the enzyme responsible for conversion of testosterone to estradiol. Concomitant suppression of SRD5A2 and treatment with TNF-α synergistically up-regulate the aromatase levels. The data suggest that in the absence of prostatic SRD5A2 there is an androgenic to estrogenic switch. These findings have broad implications for choosing appropriate classes of medications for management of benign and malignant prostatic diseases.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2jKA1jn