Effect of Reduced Blood Cholesterol on Sterol and Steroid Metabolism by Rat Luteal Tissue*

Abstract

The role of blood cholesterol in ovarian function was studied by treating superovulated rats with 4-aminopyrazolo [3,4,-cd]pyrimidine (APP) a drug which inhibits hepatic secretion of lipoproteins. Reduction of plasma cholesterol and progesterone concentrations and ovarian content of cholesteryl esters were related to dose and duration of APP treatment; ovarian concentrations of free cholesterol, phospholipids, and triglycerides and ovarian weight were not altered. Progestin content of luteal tissue was also reduced by APP treatment. These changes were reversible, since concentrations of plasma progesterone and cholesterol and ovarian concentrations of cholesteryl esters returned to control values 5 days after stopping treatment. Dispersed ovarian cells from APP-treated rats incorporated [¹⁴C]- acetate into free cholesterol at a 10-fold greater rate than control cells. Luteal cells from both groups incorporated [¹⁴C]acetate into cholesteryl esters, phospholipids, triglycerides, and ¹⁴CO₂ at similar rates. Incorporation of [¹⁴C]acetate into progesterone and 20α-hydroxy-4-pregnen-3-one progressed at a greater rate in luteal cells from treated rats than in controls. Although progestin production by cells from treated rats was lower than controls, LH and dibutyryl cAMP stimulated progestin secretion 5-fold in each group. Activity of ovarian 3-hydroxy-3-methylglutaryl coenzyme A reductase increased 20-fold after APP treatment. These findings indicate that plasma cholesterol is the primary source of sterol for steroid production and accumulation of cholesteryl ester by luteal cells. Furthermore, the availability of blood cholesterol appears to regulate the rate of de novo biosynthesis of cholesterol and progestins.