5α-Androstane-3β,17β-diol (3β-diol), an estrogenic metabolite of 5α-dihydrotestosterone, is a potent modulator of estrogen receptor ERβ expression in the ventral prostrate of adult rats

Prostate is one of the major targets for dihydrotestosterone (DHT), however this gland is also recognized as a nonclassical target for estrogen as it expresses both types of estrogen receptors (ER), especially ERβ. Nevertheless, the concentrations of aromatase and estradiol in the prostate are low, indicating that estradiol may not be the only estrogenic molecule to play a role in the prostate. It is known that DHT can be metabolized to 5α-androstane-3β,17β-diol (3β-diol), a hormone that binds to ERβ but not to AR. The concentration of 3β-diol in prostate is much higher than that of estradiol. Based on the high concentration of 3β-diol and since this metabolite is a physiological ERβ ligand, we hypothesized that 3β-diol would be involved in the regulation of ERβ expression. To test this hypothesis, adult male rats were submitted to castration followed by estradiol, DHT or 3β-diol replacement. ERβ and AR protein levels in the prostate were investigated by immunohistochemistry and Western blotting assays. The results showed that after castration, the structure of the prostate was dramatically changed and ERβ and AR protein levels were decreased. Estradiol had just minor effects on the parameters analyzed. DHT-induced partial recovery of ERβ while it was the most effective inductor of AR expression. Replacement with 3β-diol-induced the highest levels of ERβ, but was comparatively less effective in recovering the AR expression and the gland structure. These results offer evidence that one functional role of 3β-diol in the prostate may be autoregulation of its natural receptor, ERβ.