Metabolism of cholesteryl ester in monolayers of bovine adrenal cortical cells. Effect of an inhibitor of acyl-CoA: cholesterol acyltransferase.

The effect of Sandoz compound 58-035 on cholesterol metabolism in monolayers of bovine adrenal cortical cells was studied. 58-035 did not inhibit cholesterol ester hydrolase, cholesterol side-chain cleavage, cholesterol synthesis from acetate, or cortisol synthesis in cells stimulated with ACTH or in unstimulated cells. It was, however, an effective inhibitor of formation of cholesteryl ester. The rate of formation of cholesteryl ester in the cells was increased by additional cholesterol derived from mevalonic acid or from the hydrolysis of intracellular lipid droplets. 58-035 caused an increase in the secretion of cortisol from cells maintained on a limited supply of cholesterol from bovine lipoproteins added to the medium when the cells were not stimulated with ACTH. This effect was not observed in stimulated cells. The results suggest that the bovine adrenal cortical cell can direct the flux of exogenous cholesterol very precisely according to its metabolic state.