title: Scavenger receptor-B1 and luteal function in mice.
abstract: During luteinization, circulating high-density lipoproteins supply cholesterol to ovarian cells via the scavenger receptor-B1 (SCARB1). In the mouse, SCARB1 is expressed in cytoplasm and periphery of theca, granulosa, and cumulus cells of developing follicles and increases dramatically during formation of corpora lutea. Blockade of ovulation in mice with meloxicam, a prostaglandin synthase-2 inhibitor, resulted in follicles with oocytes entrapped in unexpanded cumulus complexes and with granulosa cells with luteinized morphology and expressing SCARB1 characteristic of luteinization. Mice bearing null mutation of the Scarb1 gene (SCARB1(-/-)) had ovaries with small corpora lutea, large follicles with hypertrophied theca cells, and follicular cysts with blood-filled cavities. Plasma progesterone concentrations were decreased 50% in mice with Scarb1 gene disruption. When SCARB1(-/-) mice were treated with a combination of mevinolin [an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase (HMGR)] and chloroquine (an inhibitor of lysosomal processing of low-density lipoproteins), serum progesterone was further reduced. HMGR protein expression increased in SCARB1(-/-) mice, independent of treatment. It was concluded that theca, granulosa, and cumulus cells express SCARB1 during follicle development, but maximum expression depends on luteinization. Knockout of SCARB1(-/-) leads to ovarian pathology and suboptimal luteal steroidogenesis. Therefore, SCARB1 expression is essential for maintaining normal ovarian cholesterol homeostasis and luteal steroid synthesis.
authors.affiliation: Centre de Recherche en Reproduction Animale, Université de Montréal, Québec, Canada.
authors.forename: Leonor Miranda
authors.initials: LM
authors.lastname: Jiménez
authors.forename: Mario
authors.initials: M
authors.lastname: Binelli
authors.forename: Kalyne
authors.initials: K
authors.lastname: Bertolin
authors.forename: R Marc
authors.initials: RM
authors.lastname: Pelletier
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Murphy
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D006062:Gonadotropins / Q000494:pharmacology; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D051379:Mice; D010060:Ovulation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*
chemical_list: D006062:Gonadotropins; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol
references.citation: Biol Reprod. 2010 Feb;82(2):402-12
references.pmid: 19726735
references.citation: Curr Opin Lipidol. 2004 Jun;15(3):287-95
references.pmid: 15166784
references.citation: Biol Reprod. 2008 Sep;79(3):475-85
references.pmid: 18480464
references.citation: J Lipid Res. 2001 Feb;42(2):170-80
references.pmid: 11181745
references.citation: Mol Cell Endocrinol. 2005 Apr 29;234(1-2):75-9
references.pmid: 15836955
references.citation: Biol Reprod. 2000 Jul;63(1):2-11
references.pmid: 10859235
references.citation: Endocrinology. 2002 Feb;143(2):708-16
references.pmid: 11796528
references.citation: J Anim Sci. 1998 Apr;76(4):1216-31
references.pmid: 9581947
references.citation: Biol Reprod. 2009 Feb;80(2):328-36
references.pmid: 18829706
references.citation: Ann N Y Acad Sci. 2001 Dec;948:1-8
references.pmid: 11795387
references.citation: Oxf Rev Reprod Biol. 1989;11:179-223
references.pmid: 2560824
references.citation: Am J Physiol Endocrinol Metab. 2007 Oct;293(4):E1053-61
references.pmid: 17698983
references.citation: Endocrinology. 2006 Apr;147(4):1577-88
references.pmid: 16410302
references.citation: Neurosci Lett. 2003 Mar 13;339(1):62-6
references.pmid: 12618301
references.citation: Endocrinology. 2009 Feb;150(2):957-65
references.pmid: 18832102
references.citation: J Clin Invest. 2001 Dec;108(11):1717-22
references.pmid: 11733567
references.citation: J Cell Sci Suppl. 1985;3:131-7
references.pmid: 3914990
references.citation: Endocrinology. 1998 Jul;139(7):3043-9
references.pmid: 9645674
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9322-7
references.pmid: 10430941
references.citation: J Biol Chem. 1998 Nov 20;273(47):31002-8
references.pmid: 9812997
references.citation: J Lipid Res. 2008 May;49(5):1024-33
references.pmid: 18272928
references.citation: Biochem Pharmacol. 1974 Sep 15;23(18):2495-531
references.pmid: 4606365
references.citation: Development. 2008 Jan;135(1):111-21
references.pmid: 18045843
references.citation: Biochem J. 2001 Jun 1;356(Pt 2):317-25
references.pmid: 11368757
references.citation: Nucleic Acids Res. 2001 May 1;29(9):e45
references.pmid: 11328886
references.citation: Contraception. 2003 Jun;67(6):485-9
references.pmid: 12814819
references.citation: J Lipid Res. 1998 Aug;39(8):1616-28
references.pmid: 9717722
references.citation: Genes Dev. 2008 Jul 15;22(14):1871-6
references.pmid: 18628394
references.citation: Endocrinology. 1997 Aug;138(8):3540-7
references.pmid: 9231809
references.citation: Biochim Biophys Acta. 1999 Jan 4;1436(3):565-76
references.pmid: 9989286
references.citation: J Clin Endocrinol Metab. 1998 Mar;83(3):983-91
references.pmid: 9506760
references.citation: Endocrinology. 2003 Jun;144(6):2437-45
references.pmid: 12746305