Azhar S, Tsai L, Medicherla S, Chandrasekher Y, Giudice L, Reaven E
Geriatric Research, Education, and Clinical Center, Veterans Administration Palo Alto Health Care System, California 94304, USA.
J Clin Endocrinol Metab. 1998 Mar;83(3):983-91. doi: 10.1210/jcem.83.3.4662.
This study examines the ability of human high density lipoproteins (HDL3) to deliver cholesteryl esters to human granulosa cells and describes 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 or fluorescently labeled HDL cholesteryl esters) to determine whether cells from humans (in which HDL is not the primary circulating lipoprotein species) can nevertheless interiorize and appropriately process cholesteryl esters for steroidogenesis. The results indicate that hormone-stimulated granulosa cells actively and efficiently use human HDL-derived cholesterol for progesterone production. More than 95% of the mass of HDL cholesteryl esters entering cells does so through the nonlysosomal (selective) pathway, i.e. cholesteryl esters released from HDL are taken up directly by the cells without internalization of apoproteins. Once internalized, the cholesteryl esters are either hydrolyzed and directly used for steroidogenesis or stored in the cells as cholesteryl esters until needed. The utilization of the internalized cholesteryl esters is a hormone-regulated event; i.e. luteinized human granulosa cells internalize and store large quantities of HDL-donated cholesteryl esters when available, but further processing of the cholesteryl esters (hydrolysis, re-esterification, or use in steroidogenesis) does not occur unless the cells are further stimulated to increase progesterone secretion.
本研究检测了人高密度脂蛋白（HDL3）向人颗粒细胞递送胆固醇酯的能力，并描述了这一过程所通过的选择性胆固醇途径。将从接受体外受精 - 胚胎移植手术的受试者获得的黄体化细胞与天然HDL3（或放射性标记或荧光标记的HDL胆固醇酯）一起孵育，以确定来自人类的细胞（其中HDL不是主要的循环脂蛋白种类）是否仍能内化并适当处理胆固醇酯以进行类固醇生成。结果表明，激素刺激的颗粒细胞积极且有效地利用源自人HDL的胆固醇来产生孕酮。进入细胞的HDL胆固醇酯质量的95%以上是通过非溶酶体（选择性）途径进行的，即从HDL释放的胆固醇酯被细胞直接摄取，而载脂蛋白不被内化。一旦内化，胆固醇酯要么被水解并直接用于类固醇生成，要么作为胆固醇酯储存在细胞中以备后用。内化的胆固醇酯的利用是一个受激素调节的过程；即，黄体化的人颗粒细胞在有可用的HDL捐赠的胆固醇酯时会内化并储存大量此类物质，但除非细胞受到进一步刺激以增加孕酮分泌，否则胆固醇酯不会进一步加工（水解、再酯化或用于类固醇生成）。
