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

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Abstract
The ability of 2 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 2 enzyme activities. 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 nonsteroidal 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. The influence of 5.alpha.-dihydrotestosterone administration on these enzyme activities in male rats was not prevented.