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.