Cholesteryl ester hydrolysis in rat liver lysosomes: different response to female sex hormones.

The regulation of the hydrolysis of cholesteryl oleate by female sex hormones was studied in the lysosomal fraction of rat liver. Cholesterol ester hydrolase activity was determined at pH 5.0 with an acetone-dissolved cholesteryl [1-14C]oleate substrate preparation. The administration of a single dose of progesterone decreased the enzyme activity during a 3- to 24-hr period following hormone injection. This effect was not correlated to changes in the lysosomal protein synthesis rate. The lysosomal hydrolysis of cholesteryl esters was also inhibited in a noncompetitive manner by the addition of progesterone at concentrations higher than 100 microM. The esterase failed to respond to the estradiol in vivo as well as in vitro. The findings of the present paper suggest that the lysosomal breakdown of cholesteryl esters in rat liver may be under selective hormonal regulation and that the inhibitory effect of progesterone on the enzyme activity might be, at least in part, responsible for the liver cholesterol ester accumulus produced by the administration of the hormone.