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

Abstract

Abstract. The ability of two antiandrogens, cyproterone acetate and flutamide, to block the induction of microsomal 3β-hydroxysteroid dehydrogenase and repression of microsomal 5α-reductase in rat liver following administration of 5α-dihydrotestosterone was investigated in male and female castrated and female gonadintact rats. Although both antiandrogens blocked the effects of 5α-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 5α-dihydrotestosterone, the induction of 3β-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 5α-dihydrotestosterone mediated changes in the enzyme activities of female rats regardless of gonadal status. However the influence of 5α-dihydrotestosterone administration on these enzyme activities in male rats was not prevented.