Androgen Receptor Dependent and Independent Activities of Testosterone on Hepatic Microsomal Drug Metabolism12

Publisher Website
Google Scholar
Abstract
Administration of testosterone for 6 days to intact female and castrate male BALB/cJ mice stimulated hepatic microsomal ethylmorphine N-demethylase activity and cytochrome P-450 content by 50-75%. Testosterone also stimulated hepatic microsomal NADPH-oxidase activity, but to a lesser degree. To probe the mechanism of this effect of androgens, 2 antiandrogens (cyproterone acetate and flutamide) were employed. Since cyproterone acetate was a potent stimulator of hepatic microsomal ethylmorphine N-demethylase activity and cytochrome P-450 content, no antiandrogenic activity of this steroid could be detected. Flutamide alone had little effect on either ethylmorphine N-demethylase activity or cytochrome P-450 content. This drug effectively blocked the stimulatory effects of testosterone on ethylmorphien N-demethylase activity and cytochrome P-450 content but not on NADPH-oxidase activity. This effect was not species specific, since flutamide also prevented androgen stimulation of ethylmorphine metabolism in adult castrate and prepubertal male Fisher rats. The testosterone-induced increase of hepatic weight and microsomal protein content was not affected by the administration of flutamide. Androgens have 2 distinct effects on the liver. Testosterone may act as a general, nonspecific stimulant of liver wt and microsomal protein content which is independent of the androgen receptor. Testosterone action in the liver may be expressed via an androgen-specific or androgen receptor-dependent mechanism which controls, in part, the cytochrome P-450-dependent demethylase system.

This publication has 0 references indexed in Scilit: