Partial feminization of hepatic steroid metabolism in male rats after neonatal administration of cyproterone acetate.
The metabolism of (4-14C)4-androstene-3,17-dione, (4-14C)5alpha-androstane-3alpha, 17beta-diol and (1,2-3H)5alpha-androstane-3alpha, 17beta-diol 3,17-disulphate was studied using the microsomal fraction and the metabolism of (4-14C)4-androstene-3,17-dione was studied using the 105 000 g supernatant fraction of liver from male and female rats aged 5 months that had been treated with cyproterone acetate before (from day 13 of pregnancy) and after birth (until 3 weeks of age). Nearly all sex-dependent enzyme activities in the treated male rats were changes in a direction characteristic of female rats: 5alpha-reductase active on 4-androstene-3,17-dione increased in activity whereas 3beta- and 17alpha-hydroxysteroid reductases and 6beta- and 16alpha-hydroxylases active on 4-androstene-3,17-dione and 2alpha-, 2beta- and 18-hydroxylases active on 5alpha-androstane-3alpha,17beta-diol decreased in activity. Enzyme activities not under gonadal control, i.e. 3alpha- and 17beta-hydroxysteroid reductases active on 4-androstene-3,17-dione and 7alpha-hydroxylase active on both 4-androstene-3,17-dione and 5alpha-androstane-3alpha, 17beta-diol, were not affected by cyproterone acetate. The liver enzyme activities in treated female rate were generally not affected although significant effects were noted in two cases; in one of these (17alpha-hydroxysteroid reductase) a testosterone-like effect was observed. The results obtained are probably best explained in the following way: treatment with theanti-androgen during the neonatal period results in less efficient imprinting of the hypothalamo-hypophysial system leading to less pronounced masculine setting of sex-dependent enzyme levels and also to a relative androgen unresponsiveness. It is suggested that the biochemical methods used in the degree of neonatal sexual differentiation of the hypothalamo-hypophysial system than biological and psychological methods previously available.
D000731:Androstanes / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002585:Cesarean Section; D002850:Chromatography, Gel; D002855:Chromatography, Thin Layer; D003534:Cyproterone / Q000494:pharmacology*; D005262:Feminization / Q000139:chemically induced*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D006914:Hydroxysteroids / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D012611:Scrotum / Q000187:drug effects; D012737:Sex Factors
D000731:Androstanes; D006914:Hydroxysteroids; D000735:Androstenedione; D003534:Cyproterone; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D006913:Hydroxysteroid Dehydrogenases