THYROID-HORMONE RAPIDLY INCREASES CHOLESTEROL 7-ALPHA-HYDROXYLASE MESSENGER-RNA LEVELS IN HYPOPHYSECTOMIZED RATS

The induction of hepatic cholesterol 7 alpha-hydroxylase mRNA by triiodothyronine was investigated in hypophysectomized rats. These rats exhibited markedly decreased levels of cholesterol 7 alpha-hydroxylase mRNA compared to normal controls. An increase in this mRNA could be detected within 30 min after giving triiodothyronine. A triiodothyronine dose of 0.25 mu g per 100 g of body weight, which produces 50% occupancy of hepatic nuclear thyroid hormone receptors, caused significant increases in hydroxylase mRNA levels. The half-life of cholesterol 7 alpha-hydroxylase mRNA was about 30 min and was not affected by thyroid hormone. Administration of the protein synthesis inhibitor, cycloheximide, after triiodothyronine caused superinduction. Hepatic HMG-CoA reductase mRNA levels, which are also low in livers from hypophysectomized rats, were unaffected by these doses of hormone within the 2 h time-frame examined in these studies. The results suggest that thyroid hormone may exert a primary affect on the expression of the hepatic cholesterol 7 alpha-hydroxylase gene. This could explain, in part, the hypocholesterolemic effect of thyroid hormone.