The reverse cholesterol transport system as a potential mediator of luteolysis in the primate corpus luteum

• Published in: Reproduction (Cambridge, England) Vol. 139; no. 1; pp. 163 - 176
• Main Authors: Bogan, Randy L, Hennebold, Jon D
• Format: Journal Article
• Language: English
• Published: England BioScientifica 01.01.2010; BioScientifica Ltd; Society for Reproduction and Fertility
• Subjects: Animals; apolipoprotein A-I; Apolipoproteins; Apolipoproteins - genetics; Apolipoproteins - metabolism; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; blood proteins; Cell Size; cholesterol; Cholesterol - metabolism; Corpus Luteum; Corpus Luteum - cytology; Corpus Luteum - metabolism; Corpus Luteum - physiology; cytology; Female; Gene Expression Regulation; genes; genetics; high density lipoprotein; homeostasis; Immunohistochemistry; Lipid Metabolism; Lipoproteins; Lipoproteins - metabolism; Lipoproteins - physiology; liver; luteal cells; Luteal Phase; Luteal Phase - metabolism; luteolysis; Luteolysis - metabolism; Luteolysis - physiology; Macaca mulatta; messenger RNA; metabolism; Oligonucleotide Array Sequence Analysis; Organ Specificity; phospholipids; physiology; progesterone; Protein Transport; receptors; Receptors, Lipoprotein; Receptors, Lipoprotein - genetics; Receptors, Lipoprotein - metabolism; RNA, Messenger; RNA, Messenger - metabolism; steroidogenesis
• ISSN: 1470-1626; 1741-7899; 1741-7899
• DOI: 10.1530/REP-09-0005

The cessation of progesterone (P4) production (i.e. functional regression), arguably the key event in luteolysis of the primate corpus luteum (CL), is poorly understood. Previously, we found that genes encoding proteins involved in cholesterol uptake decreased, while those involved in cholesterol efflux (reverse cholesterol transport, RCT) increased in expression during spontaneous functional regression of the rhesus macaque CL, thereby potentially depleting the cholesterol reserves needed for steroidogenesis. Therefore, a comprehensive analysis of the components necessary for RCT was performed. RCT components were expressed (mRNA and/or protein) in the macaque CL including cholesterol sensors (liver X receptors α or NR1H3; and β or NR1H2), efflux proteins (ATP-binding cassette subfamilies A1 (ABCA1) and G1), acceptors (apolipoproteins A1 or APOA1; and E or APOE), and plasma proteins facilitating high-density lipoprotein formation (lecithin:cholesterol acyltransferase or LCAT; phospholipid transfer protein or PLTP). ABCA1, APOE, PLTP, and NR1H3 increased, while lipoprotein receptors decreased, in expression (mRNA and/or protein) through the period of functional regression. The expression of APOA1 and APOE, as well as NR1H3, was greatest in the CL and tissues involved in regulating cholesterol homeostasis. Immunolocalization studies revealed that RCT proteins and lipoprotein receptors were expressed in large luteal cells, which possess intracellular cholesterol reserves during periods of P4 synthesis. Lipid staining revealed changes in luteal cholesterol ester/lipid distribution that occurred following functional regression. These results indicate that decreased cholesterol uptake and increased RCT may be critical for the initiation of primate luteolysis by limiting intracellular cholesterol pools required for steroidogenesis.