Hormonal and developmental regulation of expression of the hepatic microsomal steroid 16α-hydroxylase cytochrome P-450 apoprotein in the rat

The hormonal regulation of the sexually differentiated cytochrome P-450 isoenzyme which catalyzes 16α-hydroxylation of testosterone and 4-androstene-3,17-dione in male rat liver (P-450(16α)) was investigated. Estradiol valerate injection of male rats caused a decrease in P-450(16α) levels to almost the female level, while methyltrienolone injection had the reverse effect in female animals. Hypophysectomy abolished the sex difference in P-450(16α) levels. Human growth hormone infusion into male rats, mimicking the female pattern of growth hormone secretion, caused a feminization of P-450(16α) levels. The same effect was also seen in hypophysectomized rats of both sexes. In contrast, a different administration schedule involving 12 h injections of human growth hormone, mimicking the male pattern of growth hormone secretion, caused a masculinization of P-450(16α) levels in hypophysectomized rats, at a daily dose which causes feminization when given by infusion. Thus, the level of expression of P-450(16α) in the liver is dependent on the temporal pattern of blood growth hormone levels. While infusion of rat growth hormone into male rats also feminized the P-450(16α) levels, infusion of ovine prolactin had no effect. Ontogenic studies showed that the developmental pattern of P-450(16α) expression in the liver coincided with the known pattern of development of the sexual differentiation of hepatic steroid 16α-hydroxylase activity and of the diurnal pattern of growth hormone secretion.