Effects of thyroidectomy and triiodothyronine administration on rat liver alcohol dehydrogenase

Abstract

The effect of thyroidectomy on the activity of liver alcohol dehydrogenase and on the rate of ethanol elimination was determined in the rat. Thyroidectomy resulted in a marked increase in liver alcohol dehydrogenase activity. Three isoenzymes of alcohol dehydrogenase activity were demonstrated in thyroidectomized animals by starch gel electrophoresis, as compared with two in sham-operated control animals. Triiodothyronine administration decreased the enzyme activity in control animals, and suppressed the enhanced activity in thyroidectomized animals. Inhibition of alcohol dehydrogenase by triiodothyronine in vitro was found to be competitive with respect to NAD+ and uncompetitive with respect to ethanol in both control and thyroidectomized animals. Thyroidectomy did not result in any changes in the rate of ethanol elimination. The cytosolic free NAD+/NADH ratio decreased after ethanol administration in both control and thyroidectomized animals, while the mitochondrial-free NAD+/NADH ratio decreased only in the control animals. These results indicate that the thyroid is a repressor of liver alcohol dehydrogenase activity. A defect in the transfer of reducing equivalents from the cytosol to the mitochondria appears to limit the rate of ethanol elimination in thyroidectomized animals with increased liver alcohol dehydrogenase activity.