5alpha-reduction of an anti-androgen TSAA-291, 16beta-ethyl-17beta-hydroxy-4-estren-3-one, by nuclear 5alpha-reductase in rat prostates.
Inhibition of 5alpha-reduction of testosterone by an anti-androgen TSAA-291 (16beta-ethyl-17beta-hydroxy-4-estren-3-one) was studied in rat ventral prostates and the metabolic conversion of 3H-TSAA-291 was examined both in vitro and in vivo. In the in vitro experiment using nuclear 5alpha-reductase of the prostate, 5alpha-dihydrostestosterone formation from 3H-testosterone was inhibited in a competitive manner by the anti-androgen. In the in vitro experiment using 3H-TSAA-291, 5alpha-reduction of the anti-androgen occurred. One, 2 and 4 hr after an intravenous administration of 140 muCi/rat of 3H-TSAA-291 to castrated rats, the unchanged TSAA-291 accumulated in higher amounts in the ventral prostate than in the plasma, skeletal muscle and levator ani muscle, thereby indicating the selective uptake of the anti-androgen by the androgen target organ. No appreciable amounts of the 5alpha-reduced metabolite of TSAA-291 were detected in the prostate, thus suggesting that TSAA-291 itself may be responsible for the anti-androgenic properties. The inhibitory potency of the 5alpha-reductase activity of several other 16beta-substituted androstane and estrane analogues was also examined.
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D002855:Chromatography, Thin Layer; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011467:Prostate / Q000201:enzymology*; D051381:Rats; D013739:Testosterone / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D013739:Testosterone; D009277:Nandrolone; D010088:Oxidoreductases; C005671:oxendolone