Hormonal and developmental regulation of expression of the hepatic microsomal steroid 16 alpha-hydroxylase cytochrome P-450 apoprotein in the rat.
The hormonal regulation of the sexually differentiated cytochrome P-450 isozyme which catalyzes 16 alpha-hydroxylation of testosterone and 4-androstene-3,17-dione in male rat liver (P-450(16) alpha) was investigated. Estradiol valerate injection of male rats caused a decrease in P-450(16) alpha levels to almost the female level, while methyltrienolone injection had the reverse effect in female animals. Hypophysectomy abolished the sex difference in P-450(16) alpha levels. Human growth hormone infusion into male rats, mimicking the female pattern of growth hormone secretion, caused a feminization of P-450(16) alpha 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(16) alpha levels in hypophysectomized rats, at a daily dose which causes feminization when given by infusion. Thus, the level of expression of P-450(16) alpha 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(16) alpha levels, infusion of ovine prolactin had no effect. Ontogenic studies showed that the developmental pattern of P-450(16) alpha expression in the liver coincided with the known pattern of development of the sexual differentiation of hepatic steroid 16 alpha-hydroxylase activity and of the diurnal pattern of growth hormone secretion.
D000375:Aging; D000818:Animals; D001059:Apoproteins / Q000096:biosynthesis*; D001189:Aryl Hydrocarbon Hydroxylases; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D000072467:Cytochrome P450 Family 2; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D007016:Hypophysectomy; D008099:Liver / Q000254:growth & development*; D008297:Male; D015741:Metribolone; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D011388:Prolactin / Q000494:pharmacology; D051381:Rats; D012733:Sex Differentiation / Q000187:drug effects; D012737:Sex Factors; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000096:biosynthesis*; D045165:Testosterone Congeners / Q000494:pharmacology*
D001059:Apoproteins; D004963:Estrenes; D045165:Testosterone Congeners; D015741:Metribolone; D004958:Estradiol; D011388:Prolactin; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase