SR-BI and HDL cholesteryl ester metabolism

Scavenger receptor class B, type I (SR-BI) is the receptor for high density lipoprotein (HDL) that mediates cellular uptake of HDL cholesteryl ester (CE) and is a major route for cholesterol delivery to steroidogenic pathways. SR-BI is localized in specialized microvillar channel plasma membrane compartments that retain HDL and are sites for HDL CE selective uptake. In fact, adrenal gland microvillar channel formation is regulated by adrenocorticotropin hormone and requires SR-BI expression. SR-BI-mediated uptake of HDL CE is a two-step process requiring high affinity HDL binding followed by transfer of CE to the membrane. SR-BI delivers HDL CE to sites in the membrane where it is readily metabolized to free cholesterol by cell type-specific neutral CE hydrolases. The most likely candidate for the hydrolysis of HDL CE delivered via SR-BI in the adrenal gland is hormone sensitive lipase. New data in adrenocortical cells as well as the study of a mutant SR-BI receptor lend insight into the mechanism of cholesterol transfer from plasma HDL to the steroidogenic pathway in endocrine cells.