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 mu mol/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 [H-3]-leucine into the enzyme protein. Dihydrotestosterone did not alter the initial 2-hour incorporation of [H-3]-leucine into the enzyme protein, Dihydrotestosterone, however, resulted in an increase in the fractional rate of degradation (K-d) 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 (K-s) 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.