Identification of a scavenger receptor in rat luteal cells which recognizes chemically modified lipoproteins and mediates the uptake of cholesterol for steroidogenesis.
The presence of the acetyl low density lipoprotein (acetyl-LDL), or scavenger receptor, which binds modified forms of LDL, was examined in rat luteal cells. Acetyl-LDL supported progesterone production by dispersed rat luteal cells at least equal to that of the native LDL under basal conditions and in the presence of human chorionic gonadotropin (hCG). The acetyl-LDL-supported progesterone production was stimulated by hCG and dibutyryl cAMP in a concentration-dependent manner. Studies on acetyl-LDL binding to ovarian plasma membranes revealed a single class of binding sites with high affinity. The binding is specific in that unlabeled acetyl-LDL and fucoidin, a known competitor for binding to scavenger receptor, were effective competitors, while native LDL was not. Furthermore, degradation of 125I-acetyl-LDL by cultured luteal cells was inhibited by unlabeled acetyl-LDL and fucoidin but not native LDL. The experiments on cross-competition between acetyl-LDL and tetranitromethane-modified high density lipoprotein (TNM-HDL) indicated that TNM-HDL is also recognized as a ligand by this receptor. In addition, in vivo pretreatment of rats with hCG resulted in induction of acetyl-LDL binding activity of ovarian plasma membranes in a time-dependent manner when compared to saline injected controls. The increase in binding activity was due to an increase in the number of binding sites rather than to a change in the binding affinity. In conclusion, this study demonstrates that, in addition to receptor-mediated LDL and HDL pathways, rat luteal cells possess a scavenger receptor pathway, which recognizes TNM-HDL as well as acetyl-LDL. This receptor may play an important role in the uptake and utilization of modified lipoprotein-associated cholesterol by luteal cells.
Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor 48109-0278.
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Menon
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000378:metabolism; D003338:Corpus Luteum / Q000378:metabolism*; D005260:Female; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000032:analysis*; D015854:Up-Regulation
D008078:Cholesterol, LDL; D006063:Chorionic Gonadotropin; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; C032629:acetyl-LDL; D011374:Progesterone