Effect of dihydrotestosterone on turnover of alcohol dehydrogenase in rat hepatocyte culture

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
E MezeyJames J Potter

Abstract

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.

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Citations

Jan 29, 2002·Pharmacology, Biochemistry, and Behavior·Jorge JuárezMaricela Virgen
Jan 5, 2001·Alcoholism, Clinical and Experimental Research·J PinaireD W Crabb
May 8, 2000·Alcoholism, Clinical and Experimental Research·E Mezey
Sep 26, 2000·Alcoholism, Clinical and Experimental Research·A ColantoniD H Van Thiel
Jun 8, 2001·Alcoholism, Clinical and Experimental Research·N SatoV A Ramchandani
Jul 17, 2001·Biochemical and Biophysical Research Communications·E MezeyJ J Potter
Jun 28, 2014·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Manuela GrazianiRobert Nisticò
Feb 19, 2011·Chemico-biological Interactions·Aída Hernández-TobíasHéctor Riveros-Rosas
Dec 15, 2007·Forensic Science International : Synergy·A DettlingH-Th Haffner
Oct 21, 2005·Biochemical and Biophysical Research Communications·Esteban MezeyJames J Potter
Aug 16, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·Francis R SimonEileen Sutherland

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