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 μmol/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 [ 3 H]‐leucine into the enzyme protein. Dihydrotestosterone did not alter the initial 2‐hour incorporation of [ 3 H]‐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.