Depression of alcohol dehydrogenase activity in rat hepatocyte culture by dihydrotestosterone.
Hepatocytes harvested from castrated rats retained a higher alcohol dehydrogenase (EC 1.1.1.1) activity than hepatocytes harvested from normal rats during 7 days of culture. Dihydrotestosterone (1 microM) decreased the enzyme activity, after 2 and 5 days of culture, in hepatocytes from castrated and control animals respectively. Dihydrotestosterone decreased the enzyme activity to similar values in both groups of hepatocytes by the end of 7 days of culture. Testosterone (1 microM) had no effect on the enzyme activity in normal hepatocytes and only a transitory effect in decreasing the enzyme activity in hepatocytes from castrated animals. The increases in alcohol dehydrogenase activity after castration and their suppression by dihydrotestosterone were associated with parallel changes in the rate of ethanol elimination. Additions of substrates of the malate-aspartate shuttle or dinitrophenol did not modify ethanol elimination. These observations indicate that dihydrotestosterone has a direct suppressant effect on hepatocyte alcohol dehydrogenase and that the enzyme activity is a major determinant of the rate of ethanol elimination.
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001216:Asparagine / Q000494:pharmacology; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004140:Dinitrophenols / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism; D000077604:Fomepizole; D008099:Liver / Q000201:enzymology*; D008293:Malates / Q000494:pharmacology; D008297:Male; D009919:Orchiectomy; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D013739:Testosterone / Q000494:pharmacology
D004140:Dinitrophenols; D008293:Malates; D011720:Pyrazoles; D013196:Dihydrotestosterone; D000431:Ethanol; D013739:Testosterone; D001216:Asparagine; C030298:malic acid; D000077604:Fomepizole; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase