Is growth hormone the pituitary feminizing factor mediating the actions of estradiol on hepatic drug and steroid metabolism?
Previous studies have established that the effects of estradiol (E2) on hepatic steroid and drug metabolism are demonstrable only in the presence of the pituitary gland. Studies were carried out to test the hypothesis that GH is the pituitary feminizing factor mediating the actions of E2 on hepatic metabolism. E2 and GH administered to castrated male rats had similar effects on hepatic enzymes, decreasing the oxidataive metabolism of drugs [ethylmorphine demethylation, aniline, hydroxylation, and benzo(a)pyrene hydroxylation) and increasing steroid (corticosterone) delta 4-hydrogenase activity. None of these effects of E2 or GH could be demonstrated in hypophysectomized (hypox) rats. However, GH administration to T4- or ACTH-treated hypox rats resulted in some of the changes in drug and steroid metabolism seen in animals with intact pituitary glands. The actions of GH on hepatic microsomal enzymes were fully demonstrable in hypox rats receiving both T4 and ACTH. E2 had no effects in T4 plus ACTH-treated hypox rats. These and prior observations are consistent with the hypothesis that GH mediates the actions of E2 on hepatic microsomal drug- and steroid-metabolizing enzymes. The data also indicates that the cations of GH on hepatic metabolism are dependent upon the interactions with still other endocrine factors.
D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D002369:Castration; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D007016:Hypophysectomy; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010902:Pituitary Gland / Q000502:physiology*; D051381:Rats
D004958:Estradiol; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D000815:Aniline Hydroxylase; D001579:Benzopyrene Hydroxylase; D005037:Ethylmorphine-N-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase