The metabolism of [4-14C]4-androstene-3, 17-dione, [4-14C]5α-androstane-3α, 17β-diol and 1,2-3H]5α-androstane-3α, 17β-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 changed in a direction characteristic of female rats: 5α-reductase active on 4-androstene-3, 17-dione increased in activity whereas 3β- and 17α-hydroxysteroid reductases and 6β- and 16α-hydroxylases active on 4-androstene-3, 17-dione and 2α-, 2β- and 18-hydroxylases active on 5α-androstane-3α, 17β-diol decreased in activity. Enzyme activities not under gonadal control, i.e. 3α- and 17β-hydroxysteroid reductases active on 4-androstene-3, 17-dione and 7α-hydroxylase active on both 4-androstene-3, 17-dione and 5α-androstane-3α, 17β-diol, were not affected by cyproterone acetate. The liver enzyme activities in treated female rats were generally not affected although significant effects were noted in two cases; in one of these (17α-hydroxysteroid reductase) a testosterone-like effect was observed.
The results obtained are probably best explained in the following way: treatment with the anti-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 present investigation may be used for more exact estimation of the degree of neonatal sexual differentiation of the hypothalamo-hypophysial system than biological and psychological methods previously available.
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