Hormonal effects on hepatic cholesterol biosynthesis and esterification

Abstract

The effects of castration and thyroidectomy on the hepatic concentration of free and esterified cholesterol and on the incorporation of acetate-1- 14C and cholesterol- 3H into cholesterol ester by intact liver and by a liver microsomal preparation have been studied in adult rats. After castration and thyroidectomy significantly lower concentrations of free cholesterol were found in the liver. The amount of liver cholesterol ester decreased after orchiectomy and increased after thyroidectomy. Ovariectomy had no effect on the ester concentration. To study cholesterol biosynthesis and esterification in vivo, endocrine ablated and control rats were injected with acetate-1- 14C and cholesterol- 3H and killed 1/2, 1, 2, 4 and 7 hr after injection. There was a decreased rate of incorporation of acetate-1- 14C into liver cholesterol after ovariectomy, while orchiectomy resulted in increased rate of cholesterol synthesis. Esterification of cholesterol was decreased after thyroidectomy and ovariectomy, and increased after orchiectomy. In general, castration seemed to decrease the rate of turnover of hepatic free and esterified cholesterol. Throughout the in vivo experiments, the 14C-labeled cholesterol ester fractions showed significantly higher specific activities than free cholesterol- 14C. The preferential 14C-labeling of the ester was probably due to an inhomogeneity and compartmentalization of hepatic cholesterol, and might indicate that only the most recently synthesized cholesterol- 14C was used for esterification. In the in vitro experiments, hepatic microsomal enzyme preparations from thyroid-ectomized and castrated rats showed a higher activity of cholesterol esterification than the microsomal enzymes prepared from the normal control rats. Hormone replacement therapy abolished these differences in enzymatic activity.