Effect of dihydrotestosterone on turnover of alcohol dehydrogenase in rat hepatocyte culture.
Dihydrotestosterone decreased alcohol dehydrogenase (ADH) activity and enzyme-protein in rat hepatocytes in culture. This effect was observed after the hepatocytes had been exposed to dihydrotestosterone for 3 days at concentrations of 0.5 micromol/L or higher. Dihydrotestosterone did not decrease alcohol dehydrogenase messenger RNA (mRNA) but, rather, resulted in small increases in ADH mRNA after 3 days of exposure. To further determine the mechanism for the effects of dihydrotestosterone in decreasing the enzyme, the turnover of ADH was determined after incorporation of [3H]-leucine into the enzyme protein. Dihydrotestosterone did not alter the initial 2-hour incorporation of [3H]-leucine into the enzyme protein. Dihydrotestosterone, however, resulted in an increase in the fractional rate of degradation (Kd) of the enzyme from 0.12 +/- 0.013 to 0.23 +/- 0.004 per hour (P < .001) accompanied by a much smaller increase in the fractional rate of synthesis (Ks) from 0.12 +/- 0.028 to 0.17 +/- 0.031 per hour (P > .05). Hence, the mechanism for the fall in ADH in the presence of dihydrotestosterone is an increase in enzyme degradation which is not accompanied by a sufficient increase in enzyme synthesis.
Mezey
E
E
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Rennie-Tankersley
L
L
Potter
J J
JJ
D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D013196:Dihydrotestosterone; D000426:Alcohol Dehydrogenase