Cholesterol Ester Cycle in Rat Liver: Effects of Estradiol and Progesterone

Abstract

The regulation of the enzymatic synthesis and hydrolysis of cholesteryl esters by female sex hormones has been investigated in rat liver. When the effects of estradiol and progesterone were studied in "in vitro" incubations of hepatic microsomes, a dual effect was observed. Progesterone inhibited both microsomal cholesterol ester hydrolase and acyl-CoA: cholesterol acyltransferase activities in a concentration-dependent manner; however, the presence of estradiol stimulated cholesterol ester hydrolysis while it inhibited cholesterol ester formation. The administration of pharmacological doses of estradiol for three consecutive days resulted in decreased cytosolic and microsomal cholesterol esterase activities followed by an increased microsomal cholesteryl esters content whereas acyl-CoA: cholesterol acyltransferase and other microsomal parameters remained unchanged. Examination of the effects of the short-term treatment with pharmacological doses of progesterone showed that treatment was less effective in changing the hepatic pattern of the cholesteryl esters cycle, since only cytosolic cholesterol ester hydrolase activity diminished slightly. Neither cytosolic nor microsomal cholesterol esterase or acyl-CoA: cholesterol acyltransferase were consistently affected by the administration of therapeutical doses of estradiol or progesterone for 21 days, although both the free cholesterol-phospholipid and the total cholesterol-phospholipid molar ratios decreased moderately. The effect of the hormonal vehicle, propylene glycol, on some microsomal lipid parameters is finally discussed.