Feminization of hepatic steroid metabolism in male rats following electrothermic lesion of the hypothalamus

The metabolism of [4¹⁴C]androst-4-ene-3, 17-dione, [4¹⁴C]5α-androstane-3α, 17β-diol and [l, 2³H]5α-androstane-3α, 17β-diol) 3, 17-disulfate in the 105, 000 × g supernatant and microsomal fractions of liver was studied in male and female rats after electrothermic lesion of the hypothalamus including the median eminence. Following electrothermic lesion, hepatic steroid metabolism in male rats was generally “feminized” (increased 5αreduction and decreased 6β- and 16α-hydroxylation of 4-androstene-3, 17-dione, decreased 2α-, 2β-, 18-, and 7β-hydroxylation of 5α-androstane-3α, 17β-diol and induced 15β-hydroxylation of 5α-androstane-3α, 17β-diol, 3, 17-disulfate), whereas hepatic metabolism in female rats remained essentially unchanged. Previous investigations have pointed to the occurrence of a sex-specific secretion of “feminizing factor” from the female pituitary that is responsible for the “feminization” of the basically “masculine” type of metabolism characterizing the rat liver. Taken together with these findings, the present results indicate that the release of the pituitary “feminizing factor” is controlled by means of a release-inhibiting factor from the hypothalamus. This factor is not secreted in female rats; it is suggested that its secretion in male rats is turned on as a result of neonatal imprinting by testicular androgens.