Characterization of two new enzymatic activities of the rat ventral prostate: 5α-Androstane-3β, 17β-diol 6α-Hydroxylase and 5α-androstane-3β,17β-Diol 7α-Hydroxylase

This study has characterized two new enzymatic hydroxylase activities specific for 5α-androstane-3β, 17β-diol (3β-diol) in the rat ventral prostate: 5α-androstane-3β, 17β-diol 6α-hydroxylase (6α-hydroxylase) and 5α-androstane-3β, 17β-diol 7α-hydroxylase (7α-hydroxylase). Both of these irreversible hydroxylase activities require NADPH and are localized in the microsomal fraction of the prostate. The apparent K_m for 3β-diol is 2.5 μm for both the 6α-and 7α-hydroxylase activities. The apparent K_m for NADPH is 7.6 μm for the 6α-hydroxylase and 7.0 μm for the 7α-hydroxylase. The pH optimum for both activities is 7.4. Several steroid inhibitors of these hydroxylase activities in vitro were identified including cholesterol, progesterone, and estradiol. Estradiol was found in vitro to be a noncompetitive inhibitor (K_i = 5 μM). Injection of estradiol into intact male rats, simultaneously receiving exogenous testosterone, also produced a significant lowering of the 6α-plus 7α-hydroxylase activities. Both the 6α-and 7α-hydroxylase were found to be androgen sensitive. Following castration there is a rapid decrease in both activities.