The additive effects of progestins on testosterone-stimulated hepatic ethylmorphine metabolism and cytochrome P-450 content

Abstract

The actions of several progestins on mouse liver were studied in terms of their inherent potency and for their ability to modify the biologic activity of testosterone. When hepatic ethylmorphine demethylase activity and cytochrome P-450 content were used as end points, the biological potency of progestins was ranked as follows: cyproterone acetate>progesterone>medroxyprogesterone acetate>hydroxyprogesterone caproate ⋟ controls. The induced alterations of these parameters were, therefore, unrelated to reported progestational (cyproterone acetate ⋟ medroxyprogesterone acetate>>hydroxyprogesterone caproate>progesterone) or androgenic (medroxyprogesterone acetate>cyproterone acetate = hydroxyprogesterone caproate = progesterone) actions of these steroids. A similar conclusion was reached when hepatic weight and microsomal protein content were used as end points. When progestins (0.1–10 mg/day) were administered with testosterone (0.1 mg/day), the effect of both steroids were additive. This is in contrast to their actions on other tissues such as kidney and sub-maxillary gland where progestins potentiate and inhibit androgen action. We conclude from these studies that the mechanism of action of progestins on the liver differs from that on other tissues.