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 (termed 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 class 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.
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