Changes in the activities of microsomal enzymes involved in hepatic steroid metabolism in the rat after administration of androgenic, estrogenic, progestational, anabolic and catatoxic steroids.

Several steroids (5 beta-dihydrotestosterone, 19-nortestosterone, methyltrienolone, norethisterone, medroxyprogesterone acetate, cyproterone acetate, chlormadinone acetate and 16 alpha-cyanopregnenolone) were tested for their ability to influence the activities of three sexually differentiated hepatic microsomal enzymes (3 alpha- and 3 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase) in male and female gonadectomized and intact female rats. Of the steroids tested only 5 beta-dihydrotestosterone was completely ineffective. The other tested steroids elicited varying degrees of "masculinization" with a distinct gradation of effect according to the enzyme activity measured and animal model used. 5 alpha-Reductase was the most sensitive enzyme activity and 3 alpha-hydroxysteroid dehydrogenase the least. Male castrates responded better than female castrates, and these in turn better than intact females. The mechanism of action of three of the steroids (methyltrienolone, medroxyprogesterone acetate and norethisterone) was examined. Both flutamide and estradiol were able to block the action of methyltrienolone and medroxyprogesterone acetate, but not that of norethisterone. It is concluded that methyltrienolone and medroxyprogesterone acetate probably masculinize the enzyme activities by the same mechanisms as androgens, whereas the repression of 5 alpha-reductase activity elicited by norethisterone administration involves a different route.