Regulation of rat luteal cell high density lipoprotein receptors: up-regulation in response to changes in intracellular cholesterol concentration.
High density lipoprotein (HDL)-derived cholesterol is preferentially utilized by rat luteal cells for steroid synthesis. This process is mediated, at least in part, by the HDL receptor. The regulation of the HDL receptor by intracellular cholesterol concentration in the ovary was assessed in the present study. Superovulated rats were treated with 4-aminopyrozolo [3, 4-d] pyrimidine (4-APP), which inhibits lipoprotein synthesis by the liver, to determine the effects of reduced levels of intracellular cholesterol on HDL receptor expression. Pseudopregnant rats were treated with 4-APP or the vehicle on days 3, 4, and 5 of pseudopregnancy. On day 6 rats were killed and ovarian membranes isolated for binding studies. Treatment with 4-APP resulted in almost a 50% decrease in serum cholesterol level 24 h later. A similar effect was observed on the level of ovarian esterified cholesterol. The binding of apolipoprotein E-free HDL to ovarian plasma membranes increased up to 34%. The effects of increased intracellular cholesterol on HDL receptor binding was then determined. Pseudopregnant rats received two injections of aminoglutethimide or vehicle on day 5 of pseudopregnancy at 10 h intervals for a period of 20 h. Rats were decapitated 10 h after the second injection of aminoglutethimide, and [125I] HDL binding studies were performed in ovarian plasma membranes. The treatment increased ovarian free and esterified cholesterol 27% and 70%, respectively. The number of binding sites for HDL in ovarian membranes increased up to 31% in response to the treatment. The evidence suggests that the HDL receptor may play a dual role in HDL metabolism. The receptor may increase to promote influx of cholesterol when intraovarian cholesterol stores are reduced and to promote cholesterol efflux when stores of intraovarian cholesterol are increased. Thus, HDL receptor appears to play a crucial role in the regulation of ovarian cholesterol level.
Talavera
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F
Department of Obstetrics/Gynecology, University of Michigan, Medical School, Ann Arbor 48109-0278.
Menon
K M
KM
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D003338:Corpus Luteum / Q000166:cytology / Q000378:metabolism*; D005260:Female; D007425:Intracellular Membranes / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D009994:Osmolar Concentration; D010053:Ovary / Q000378:metabolism; D011374:Progesterone / Q000097:blood / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation
D000924:Anticholesteremic Agents; D008075:Lipoproteins, HDL; D000616:Aminoglutethimide; C004420:4-aminopyrazolo(3,4-d)pyrimidine; D011374:Progesterone; D002784:Cholesterol; D000225:Adenine