EFFECTS OF THYROXINE ON THE EXPRESSION OF ALCOHOL-DEHYDROGENASE IN RAT-LIVER AND KIDNEY

We studied the effect of thyroxine on alcohol dehydrogenase activity, immunoreactive protein levels and messenger RNA levels in the livers of thyroidectomized and sham-operated male rats. Effects on kidney alcohol dehydrogenase activity were also examined. Sham-operated rats injected with 100 mug thyroxine/kg/day, which induced hyperthyroidism, showed a 30% decrease in liver and a 40% decrease in kidney alcohol dehydrogenase activity compared with sham-operated rats injected with vehicle. Hypothyroid rats exhibited a 1.5-fold increase in alcohol dehydrogenase activity in liver and kidney compared with thyroidectomized rats injected with a replacement dose of 20 mug thyroxine/kg/day. We saw a twofold and a 2.5-fold higher level of alcohol dehydrogenase activity in liver and kidney, respectively, of hypothyroid rats compared with hyperthyroid rats. These effects were not accounted for by nutritional differences; daily food intake did not differ between groups. Immunoreactive protein levels as seen on Western blots varied in the same direction as enzyme activity. Northern-blot analysis showed higher levels of liver alcohol dehydrogenase messenger RNA in hypothyroid rats compared with euthyroid rats. These studies show that liver alcohol dehydrogenase activity and protein levels are modulated by thyroxine at pathophysiologically relevant levels and that this effect is not due to changes in food intake; kidney alcohol dehydrogenase activity is regulated in parallel. The change in alcohol dehydrogenase activity appears to be controlled in part by pretranslational mechanisms in hypothyroid animals and by posttranslational mechanisms in hyperthyroid animals.