Adaptive responses of rat liver to the gestagen and anti-androgen cyproterone acetate and other inducers. I. Induction of drug-metabolizing enzymes.

Treatment of female Wistar rats with cyproterone acetate (CPA) was shown to cause pronounced increases of hepatic microsomal monooxygenase activity towards the following substrates: ethylmorphine (EM), aminopyrine (AP), benzphetamin (BPA) and benzo[a]pyrene (BP). Minor increases were seen using p-nitroanisole (pNA) and aniline (AN). Monooxygenase activity reached maximal levels within 24 h. The effects were dose-dependent, the threshold dose being about 4 mg/kg, and were reversible within 6 days. The results of comparative studies with several 'classical' microsomal enzyme inducers, i.e. pregnenolone-(16 alpha)-carbonitrile (PCN), phenobarbital (PB), alpha-hexachlorocyclohexane (alpha-HCH) and 3-methylcholanthrene (3-MC) suggest that CPA belongs to the PCN-type and alpha-HCH to the phenobarbital type of inducers. In male rats CPA induced only moderate increases of monooxygenase activities which can be explained by decreased testosterone scretion due to anti-gonadotropic effect of CPA.