Metabolism of Steroid Hormones, Sterols, and Bile Acids in Liver Microsomes from Male, Female, and Male‐Pseudohermaphroditic Rats

The metabolism of 4‐[4‐¹⁴C]androstene‐3,17‐dione and 4‐[4‐¹⁴C]pregnene‐3,20‐dione in 100000×g microsomes from livers of male, female and male pseudohermaphroditic rats was studied by thin‐layer chromatography and gas chromatography‐mass spectrometry. Sexual differences characterized the 16α‐hydroxylation, 3α ‐ and 3β‐hydroxysteroid oxidoreduction and 5α‐reduction of 4‐androstene‐3,17‐dione and the 6β‐hydroxylation, 20α‐ and 20β‐hydroxysteroid oxidoreduction and 5β‐reduction of 4‐pregnene‐3,20‐dione. In all these cases male pseudohermaphroditic rats showed identical enzyme activities to female rats. Furthermore, the following reactions participating in the biosynthesis of bile acids were studied: 7α‐hydroxylation of cholesterol, 5α‐reduction of 7α‐hydroxy‐4‐cholesten‐3‐one, 12α‐hydroxylation of 7α‐hydroxy‐4‐cholesten‐3‐one and 6β‐hydroxylation of taurochenodeoxycholic acid. Sexual differences characterized the two first‐mentioned reactions; also in these respects male pseudohermaphroditic rats were identical to female rats. The female character of the hepatic metabolism of the male pseudohermaphroditic rat may be due to the lack in these rats of a neonatal testosterone “imprinting” on the liver because of end‐organ insensitivity to testosterone and/or a deficient testicular biosynthesis of androgens.