Masculinization of Rat Liver Enzyme Activities Following Hypophysectomy

The metabolism of 5α-[4-I4C]androstane-3α,17β-diol and 4-[4-l4C]androstene-3,17-dione was studied in the microsomal fraction and that of 4-[4-l4C]androstene-3,17-dione also in the 105,000 × g supernatant fraction of livers from male and female rats that had been castrated or castrated and hypophysectomized. The microsomal metabolism of 5α-[4-14C]androstane-3α,17β-diol was also studied in livers from hypophysectomized rats treated with testosterone propionate or estradiol benzoate. Hypophysectomy led to an overall masculinization of hepatic steroid metabolism in female rats (increased activities of the 2α-,2β-,7β- and 18-hydroxylase systems active on 5α-androstane-3α,17β-diol and of the 6β- and 16α-hydroxylase systems, 3β- and 17α-hydroxysteroid reductase and 5β-reductase enzymes active on 4-androstene-3,17-dione). These findings indicate the existence of (a) hypophyseal feminizing factors) that feminize(s) the basic masculine character of the hepatic sex-dependent enzyme activities. On the other hand, the decrease in the 5α-reductase level observed after hypophysectomy of male rats may also indicate the existence of a hypophyseal masculinizing factor. The masculinizing and feminizing effects on liver enzyme activities previously observed following treatment with testosterone propionate and estradiol benzoate, respectively, were not seen in hypophysectomized rats. The estrogen unresponsiveness characterizing these rats may be explained by the lost capacity to induce secretion of (a) hypophyseal feminizing factor(s). It is speculated that the androgen unresponsiveness in hypophysectomized rats is due to the loss of (a) hypophyseal factor(s) necessary for the action of androgens in the liver cell. (Endocrinology95: 891, 1974)