Growth hormone depresses ethylmorphine demethylase activity: correlation with decreased levels of fast-turnover cytochrome P-450 in hypophysectomized female rats.
The hepatic monooxygenase system was studied in hypophysectomized female rats infused for 5 days with ovine growth hormone (GH). At 7.5 micrograms.h-1 GH decreased the total cytochrome P-450 by 16%; at 10 micrograms.h-1 it reduced both cytochrome P-450 (31%) and the activity of ethylmorphine demethylase (31%). GH did not alter the activities of NADPH cytochrome c reductase or aniline hydroxylase. The lower GH dose decreased the amount of fast- and slow-turnover P-450 by 11 and 38%, respectively, while the higher dose decreased both by 49%. The loss of demethylase activity therefore correlates with the loss of fast-turnover P-450. This component is relatively more abundant in the female (fast: slow turnover of 4.3) than the male (fast:slow turnover of 2.5). GH did not affect the half-lives of the P-450 components, suggesting that it decreases their synthesis. The P-450 concentration in microsomes from GH-treated animals did not increase after incubation with hemin, suggesting that in vivo the hormone does not lower P-450 synthesis via depression of heme. Puromycin mimicked the effect of GH and when given with the hormone their effects on the P-450 levels were multiplicative (p less than 0.05), suggesting different modes of action and that GH does not decrease P-450 by acting at translation.
Vockentanz
B M
BM
Department of Biological Sciences, University of Windsor, Ont., Canada.
Virgo
B B
BB
D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism*; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D007016:Hypophysectomy; D008099:Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D011691:Puromycin / Q000494:pharmacology; D051381:Rats
D011691:Puromycin; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D000815:Aniline Hydroxylase; D010089:Oxidoreductases, N-Demethylating; D005037:Ethylmorphine-N-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase