Inhibition of testosterone synthesis in the canine testis in vitro

Testicular 17 beta-hydroxysteroid oxidoreductase (17 beta-HOR) is one of the several enzymes necessary for the synthesis of testosterone, but is not required for either glucocorticoid or mineralocorticoid synthesis. Since specific inhibition of the testicular enzyme has potential contraceptive and experimental uses, the inhibitory effect of twenty steroids on 17 beta-HOR activity was examined in microsomal preparations of canine testes. Six steroids inhibited testosterone formation, but only 4-estrene-3,17-dione (KI = 2.4 microM) and 5-androstene-3,17-dione (KI = 6.8 microM) had significant inhibitory activity. The data suggest the following molecular characteristics necessary for competitive inhibition of 17 beta-HOR activity: (a) requirement for 17-keto group, (b) relative requirement for 3-keto group, (c) decreased inhibition with unsaturation in position 5-6, and (d) marked loss of inhibitory activity with 6 beta-, 11 beta- or 19- hydroxylation, and A-ring aromatization.