Sex-specific action of antiandrogens on androgen induced changes in hepatic microsomal 3β-hydroxysteroid dehydrogenase and 5α-reductase activity in the rat

The ability of two antiandrogens, cyproterone acetate and flutamide, to block the induction of microsomal 3 beta-hydroxysteroid dehydrogenase and repression of microsomal 5 alpha-reductase in rat liver following administration of 5 alpha-dihydrotestosterone was investigated in male and female castrated and female gonad-intact rats. Although both antiandrogens blocked the effects of 5 alpha-dihydrotestosterone on the seminal vesicles and uteri of gonadectomized rats at the doses employed, cyproterone acetate showed no antiandrogenic activity against the two enzyme activities. On the contrary when cyproterone acetate was administered alone it elicited a response similar to that seen after androgen administration; when given simultaneously with 5 alpha-dihydrotestosterone, the induction of 3 beta-hydroxysteroid dehydrogenase activity was greater than after either steroid alone. In contrast the non-steroidal antiandrogen, flutamide, which had no intrinsic effect on either enzyme activity, effectively blocked 5 alpha-dihydrotestosterone mediated changes in the enzyme activities of female rats regardless of gonadal status. However the influence of 5 alpha-dihydrotestosterone administration on these enzyme activities in male rats was not prevented.