Effects of excess dietary cholesterol on adrenal cholesterol accumulation and steroidogenesis

Rats maintained on diets containing 3% cholesterol for 10 weeks show marked increase in adrenal cholesterol content. The greatest part of the increase is in the cholesterol ester fraction (329%), although free cholesterol is also elevated (140%). Morphologically, a marked increase in the lipid droplet content of the cells is observed. The microsomal fraction was enriched in cholesterol with parallel increases in microsomal ACAT activity in both normal and supplemented groups. Neutral cytosolic cholesterol esterase is unaffected by the diet. No significant increase in cholesterol occurred in the mitochondrial fraction. However, cholesterol binding to cytochrome P450 was affected by the diet under certain conditions. Cholesterol supplementation elevates adrenal corticosteroid levels (43%). Mild stress results in greater increases in adrenal corticosteroids after dietary supplementation. Aminoglutethimide produces inhibition of the stress induced increase in adrenal corticosteroids. This inhibition is less pronounced in cholesterol supplemented animals than in normal animals. The lack of similar effects on plasma corticosteroid levels suggests that enhanced metabolism and clearance of the plasma corticosteroids may be taking place.