REGULATION OF INTRACELLULAR CHOLESTEROL LEVELS DURING PRIMATE LUTEAL REGRESSION

灵长类黄体退化过程中细胞内胆固醇水平的调节

• 批准号: 8173259
• 负责人: Jon D Hennebold
• 金额: $ 4.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173259
• 关键词: Affect; Apolipoproteins; Binding; Cholesterol; Computer Retrieval of Information on Scientific Projects Database; Conceptions; Ensure; Equilibrium; Funding; Gene Expression; Grant; High Density Lipoproteins; Institution; LXRalpha protein; Ligands; Liver; Low Density Lipoprotein Receptor; Luteal Cells; Luteolysis; Macaca mulatta; Nuclear Hormone Receptors; Output; Ovarian Cycles; Pregnancy; Primates; Production; Progesterone; Protein Isoforms; Proteins; Receptor Activation; Regulation; Research; Research Personnel; Resources; SR-BI receptor; Source; United States National Institutes of Health; corpus luteum; cytotoxic; extracellular; member; particle; receptor; reverse cholesterol transport; sensor; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Progesterone (P) is produced by the corpus luteum (CL) and is absolutely required to maintain early pregnancy in primates. In non-conception cycles, P secretion from the CL must cease (functional regression) to allow for the initiation of the next ovarian cycle. A high rate of cholesterol uptake within the CL occurs via low density lipoprotein receptor and scavenger receptor B1 to accommodate its significant level of P production (~40 mg daily). This high rate of uptake has to be closely balanced with efflux (also known as reverse cholesterol transport) to ensure that the cytotoxic effects of excessive cholesterol do not occur. Cholesterol efflux occurs as a result of the transfer of intracellular cholesterol via the ATP-binding cassette subfamily members A1 (ABCA1) and G1 (ABCG1) to extracellular acceptor apolipoproteins, which in turn, leads to the formation of high density lipoprotein particles. The expression of genes encoding proteins involved in cholesterol uptake and efflux are tightly controlled by the nuclear hormone receptors known as liver X receptors (LXR) alpha and beta. Both LXR isoforms are activated upon binding various oxysterols, cholesterol metabolites that serve as indicators of intracellular cholesterol levels. Thus, LXRs serve as cholesterol sensors that stimulate cholesterol efflux in cases of cholesterol excess. The objective of this project is to assess the level of endogenous LXR ligands, the oxysterols, within the rhesus macaque CL during the course of functional regression, and to determine whether luteal cell LXR activation affects cholesterol uptake and efflux, thereby leading to changes in P output.

这个子项目是众多研究子项目之一