On the obligatory role of the hypophysis in sexual differentiation of hepatic metabolism in rats

The hepatic metabolism of 4 [4 ¹⁴C]androstene 3,17 dione and 5α [4 ¹⁴C]androstane 3α,17β diol was studied in castrated and hypophysectomized male rats with a transplanted pituitary under the kidney capsule. The effects of testosterone propionate and estradiol benzoate on liver metabolism were also studied in these experimental animals. It was found that the autonomous pituitary secreted a ''feminizing factor'' that transformed the male type of steroid metabolism characteristic of hypophysectomized rats into a female type of metabolism. Hypophysectomized rats were unresponsive towards androgen action on the liver and did not respond with feminized hepatic metabolism after treatment with estradiol benzoate. It is concluded that estrogenic action on liver enzymes is mediated via modulation of the secretion of a central (probably hypothalamic) ''feminizing factor inhibiting factor'' and that sex hormonal effects on hepatic metabolism only occur in the presence of a pituitary in situ.