Adrenal cholesterol utilization

There are multiple systems for cellular cholesterol delivery for steroidogenesis, including uptake of lipoprotein-derived cholesterol via LDL receptor mediated endocytic pathways and SR-BI mediated “selective” pathways, as well as from endogenous cholesterol synthesis and the mobilization of stored cholesteryl esters. The vast majority of lipoprotein-derived cholesterol utilized for murine adrenal steroidogenesis is obtained via SR-BI mediated “selective” uptake of cholesteryl esters. Hormone-sensitive lipase (HSL) is responsible for neutral cholesteryl ester hydrolase activity in the adrenal and is critical for hydrolyzing stored cholesteryl esters, as well as cholesteryl esters that are selectively delivered from lipoproteins via SR-BI. Marked defects in steroid production are observed in adrenal cells from HSL knockout mice, due to an inability to process and utilize cholesteryl esters selectively derived from lipoproteins. Although the LDL receptor is responsible for receptor-mediated endocytic delivery of cholesteryl esters, adrenal steroid hormone production is normal in mice lacking LDL receptors.