HUMAN GRANULOSA-CELLS USE HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL FOR STEROIDOGENESIS

This study examines the ability of human high density lipoproteins (HD L3) to deliver cholesteryl esters to human granulosa cells and describ es the selective cholesterol pathway by which this occurs. Luteinized cells obtained from subjects undergoing in vitro fertilization-embryo transfer procedures were incubated with native HDL3 (or radiolabeled o r fluorescently labeled HDL cholesteryl esters) to determine whether c ells from humans (in which HDL is not the primary circulating lipoprot ein species) can nevertheless interiorize and appropriately process ch olesteryl esters for steroidogenesis. The results indicate that hormon e-stimulated granulosa cells actively and efficiently use human HDL-de rived cholesterol for progesterone production. More than 95% of the ma ss of HDL cholesteryl esters entering cells does so through the nonlys osomal (selective) pathway, i.e, cholesteryl esters released from HDL are taken up directly by the cells without Internalization of apoprote ins. Once internalized, the cholesteryl esters are either hydrolyzed a nd directly used for steroidogenesis or stored in the cells as cholest eryl esters until needed. The utilization of the internal:zed choleste ryl esters is a hormone-regulated event; i.e. luteinized human granulo sa cells internalize and store large quantities of HDL-donated cholest eryl esters when available, but further processing of the cholesteryl esters (hydrolysis, reesterification, or use in steroidogenesis: does not occur unless the cells are further stimulated to increase progeste rone secretion.