Reductive metabolism of 5 alpha-dihydrotestosterone by rat ventral and dorsolateral prostate: kinetic parameters of the enzymes.
In male sex accessory organs the active androgen 5 alpha-dihydrotestosterone (DHT) is metabolized to 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) and 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol) by the reductase activities of 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR; EC 1.1.1.50) and 3 beta-hydroxysteroid oxidoreductase (3 beta-HSOR; EC 1.1.1.51). After separation of radiosubstrate and products by HPLC, these enzymes activities in subcellular preparations of rat ventral and dorsolateral prostate were determined from the conversion of [3H]DHT to the radiometabolites 3 alpha-diol and 3 beta-diol and 3 beta-triols (5 alpha-androstane-3 beta, 6 alpha, 17 beta-triol plus 5 alpha-androstane-3 beta, 7 alpha, 17 beta-triol). Whereas both enzymes were found in the dorsolateral prostate, 3 beta-HSOR reductase activity was near the limit of detection in ventral prostate. Unlike the equal distribution of 3 alpha-HSOR reductase between the microsomal and cytosol fractions of the ventral prostate, both 3 alpha- and 3 beta-HSOR reductase activities of the dorsolateral prostate are mainly confined to its cytosol fraction. Km and Vmax of the 3 alpha- and 3 beta-HSOR reductases in dorsolateral prostate cytosol were 1.8 microM, 24.6 pmol.mg-1 min-1 and 25.4 microM, 45.7 pmol.mg-1 min-1, respectively. We surmise from these and earlier studies that 3 beta-HSOR reductase is the rate-limiting prostatic enzyme in the catabolic disposition of intracellular DHT.
Lee
K H
KH
Steroid Biochemistry Laboratory, Lemuel Shattuck Hospital, Jamaica Plain, MA 02130.
Ofner
P
P
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000818:Animals; D013196:Dihydrotestosterone / Q000096:biosynthesis*; D004229:Dithiothreitol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009249:NADP / Q000378:metabolism; D011467:Prostate / Q000033:anatomy & histology / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D013347:Subcellular Fractions / Q000201:enzymology
D013196:Dihydrotestosterone; D009249:NADP; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D004229:Dithiothreitol