Reductive metabolism of 5α-dihydrotestosterone by rat ventral and dorsolateral prostate: Kinetic parameters of the enzymes

In male sex accessory organs the active androgen 5α-dihydrotestosterone (DHT) is metabolized to 5α-androstane-3α,17β-diol (3α-diol) and 5α-androstane-3β,17β-diol (3β-diol) by the reductase activities of 3α-hydroxysteroid oxidoreductase(3α-HSOR; EC 1.1.1.50) and 3β-hydroxysteroid oxidoreductase (3β-HSOR; EC 1.1.1.51). After separation of radiosubstrate and products by HPLC, these enzyme activities in subcellular preparations of rat ventral and dorsolateral prostate were determined from the conversion of [ 3H]DHT to the radiometabolites 3α-diol and 3β-diol and 3β-triols (5α-androstane-3β,6α,17β-triol plus 5α-androstane-3β,7α,17β-triol). Whereas both enzymes were found in the dorsolateral prostate, 3β-HSOR reductase activity was near the limit of detection in ventral prostate. Unlike the equal distribution of 3α-HSOR reductase between the microsomal and cytosol fractions of the ventral prostate, both 3α- and 3β-HSOR reductase activities of the dorsolateral prostate are mainly confined to its cytosol fraction. K m, and V max of the 3α- and 3β-HSOR reductases in dorsolateral prostate cytosol were 1.8μM, 24.6 pmol·mg −1min −1 and 25.4 μM, 45.7 pmol·mg −1 min −1, respectively. We surmise from these and earlier studies that 3β-HSOR reductase is the rate-limiting prostatic enzyme in the catabolic disposition of intracellular DHT.