Scavenger receptor-B1 and luteal function in mice

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. 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. The cholesterol substrate required for most tissues to accomplish steroidogenesis exceeds the capacity for de novo synthesis of this sterol, and the principal means of augmentation of the supply is by importation of lipoprotein-bound cholesterol (1.Murphy B.D. Silavin S.L. Luteotrophic agents and steroid substrate utilization.Oxf. Rev. Reprod. Biol. 1989; 11: 179-223PubMed Google Scholar). Low-density lipoproteins enter cells by receptor-mediated endocytosis of the LDL complex and the LDL receptor (LDLR) (2.Goldstein J.L. Brown M.S. The LDL receptor and the regulation of cellular cholesterol metabolism.J. Cell Sci. Suppl. 1985; 3: 131-137Crossref PubMed Google Scholar). High-density lipoproteins interact with a membrane protein known as scavenger receptor-B1 (SCARB1) to effect the selective uptake of cholesterol esters from the HDL molecule into cells and the bidirectional transfer of free cholesterol (3.Connelly M.A. Williams D.L. Scavenger receptor BI: a scavenger receptor with a mission to transport high density lipoprotein lipids.Curr. Opin. Lipidol. 2004; 15: 287-295Crossref PubMed Scopus (134) Google Scholar). The relative contribution of LDL and HDL to the steroidogenic substrate pool varies among species and may vary among tissues within a species. One of the most active steroidogenic tissues is the corpus luteum (CL), formed from the components of the follicle following ovulation (4.Murphy B.D. Models of luteinization.Biol. Reprod. 2000; 63: 2-11Crossref PubMed Scopus (153) Google Scholar). In humans, circulating LDL is believed to be the major source of cholesterol for luteal steroid synthesis, but it has been shown that luteinized human granulosa cells can derive cholesterol esters from selective uptake via the HDL pathway (5.Azhar S. Tsai L. Medicherla S. Chandrasekher Y. Giudice L. Reaven E. Human granulosa cells use high density lipoprotein cholesterol for steroidogenesis.J. Clin. Endocrinol. Metab. 1998; 83: 983-991Crossref PubMed Scopus (92) Google Scholar). The HDL pathway appears to predominate in the CL of rodents (1.Murphy B.D. Silavin S.L. Luteotrophic agents and steroid substrate utilization.Oxf. Rev. Reprod. Biol. 1989; 11: 179-223PubMed Google Scholar), and SCARB1 is expressed in theca and luteal cells of the rat ovary (6.Li X. Peegel H. Menon K.M. In situ hybridization of high density lipoprotein (scavenger, type 1) receptor messenger ribonucleic acid (mRNA) during folliculogenesis and luteinization: evidence for mRNA expression and induction by human chorionic gonadotropin specifically in cell types that use cholesterol for steroidogenesis.Endocrinology. 1998; 139: 3043-3049Crossref PubMed Scopus (59) Google Scholar). SCARB1 expression in primary cultures of rat granulosa cells is tightly coupled with the uptake of cholesterol esters, again suggesting that it is the major pathway for importation in this tissue (7.Azhar S. Nomoto A. Leers-Sucheta S. Reaven E. Simultaneous induction of an HDL receptor protein (SR-BI) and the selective uptake of HDL-cholesteryl esters in a physiologically relevant steroidogenic cell model.J. Lipid Res. 1998; 39: 1616-1628Abstract Full Text Full Text PDF PubMed Google Scholar). There is a low level of expression of SCARB1 in mouse granulosa cells (8.Reaven E. Lua Y. Nomoto A. Temel R. Williams D.L. van der Westhuyzen D.R. Azhar S. The selective pathway and a high-density lipoprotein receptor (SR-BI) in ovarian granulosa cells of the mouse.Biochim. Biophys. Acta. 1999; 1436: 565-576Crossref PubMed Scopus (41) Google Scholar), and recent studies of luteinization in the pig demonstrated similar low expression of SCARB1 in the granulosa cells of the follicle (9.Miranda-Jimenez L. Murphy B.D. Lipoprotein receptor expression during luteinization of the ovarian follicle.Am. J. Physiol. Endocrinol. Metab. 2007; 293: E1053-E1061Crossref PubMed Scopus (16) Google Scholar). The latter study revealed extensive upregulation of SCARB1 in the CL following ovulation, with a high level of expression persisting through the luteal phase. In the macaque, the ovulatory stimulus causes a rapid increase in expression of both SCARB1 and LDLR, but only LDL can augment steroidogenesis after 24 h in vitro (10.Cherian-Shaw M. Puttabyatappa M. Greason E. Rodriguez A. VandeVoort C.A. Chaffin C.L. Expression of scavenger receptor-BI and low-density lipoprotein receptor and differential use of lipoproteins to support early steroidogenesis in luteinizing macaque granulosa cells.Endocrinology. 2009; 150: 957-965Crossref PubMed Scopus (19) Google Scholar). The inactivating mutation of SCARB1 in the mouse results in infertility, in the presence of a normal rate of ovulation (11.Trigatti B. Rayburn H. Vinals M. Braun A. Miettinen H. Penman M. Hertz M. Schrenzel M. Amigo L. Rigotti A. et al.Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology.Proc. Natl. Acad. Sci. USA. 1999; 96: 9322-9327Crossref PubMed Scopus (445) Google Scholar) and a reportedly normal capacity to produce progestational steroids (12.Miettinen H.E. Rayburn H. Krieger M. Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)-deficient mice.J. Clin. Invest. 2001; 108: 1717-1722Crossref PubMed Scopus (152) Google Scholar). The observation that nonviable oocytes are produced has led to the implication that the ovulatory process itself is disrupted in some way (11.Trigatti B. Rayburn H. Vinals M. Braun A. Miettinen H. Penman M. Hertz M. Schrenzel M. Amigo L. Rigotti A. et al.Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology.Proc. Natl. Acad. Sci. USA. 1999; 96: 9322-9327Crossref PubMed Scopus (445) Google Scholar, 12.Miettinen H.E. Rayburn H. Krieger M. Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)-deficient mice.J. Clin. Invest. 2001; 108: 1717-1722Crossref PubMed Scopus (152) Google Scholar). Although mechanisms remain unclear, it is intriguing that targeted overexpression of SCARB1 in the liver rescues fertility of SCARB1 null mice to nearly the levels found in wild-type mice (13.Yesilaltay A. Morales M.G. Amigo L. Zanlungo S. Rigotti A. Karackattu S.L. Donahee M.H. Kozarsky K.F. Krieger M. Effects of hepatic expression of the high-density lipoprotein receptor SR-BI on lipoprotein metabolism and female fertility.Endocrinology. 2006; 147: 1577-1588Crossref PubMed Scopus (55) Google Scholar). In addition, fertility was rescued by treatment with Probucol, a drug that lowers circulating cholesterol independent of SCARB1 (14.Mardones P. Quinones V. Amigo L. Moreno M. Miquel J.F. Schwarz M. Miettinen H.E. Trigatti B. Krieger M. VanPatten S. et al.Hepatic cholesterol and bile acid metabolism and intestinal cholesterol absorption in scavenger receptor class B type I-deficient mice.J. Lipid Res. 2001; 42: 170-180Abstract Full Text Full Text PDF PubMed Google Scholar). Further, if as noted above, the major supply of cholesterol for steroidogenesis in the CL is HDL imported via SCARB1 in mice, the means by which the ovary in the SCARB1 knockout mouse produces a functional CL remains unresolved. Given the importance of SCARB1 to steroidogenesis and ovarian function, we explored the expression of SCARB1 in the ovary through the estrous cycle in adult mice and following blockade of ovulation in gonadotropin-stimulated immature mice. Further, to determine possible associations of form and function in the absence of a functional HDL importation system, we examined the morphology of ovarian structures and responses to pharmacological perturbations of the cholesterol metabolism in mice bearing inactivating mutation of SCARB1. All animal experiments were approved by the Université de Montréal Animal Care Committee and conducted according to guidelines of the Canadian Council of Animal Care. Our initial interest was to determine patterns of expression of SCARB1 in the ovary during final stages of follicular development and luteinization. Stages of the estrous cycle were determined in mature wild-type (WT) mice of mixed C56/B6 and Balb/c lineage by examination of exfoliative cytology of the vagina. Gene and protein expressions of SCARB1 were quantified in granulosa cells, and luteal tissues were obtained by laser microdissection as described in Duggavathi et al. (15.Duggavathi R. Volle D.H. Mataki C. Antal M.C. Messaddeq N. Auwerx J. Murphy B.D. Schoonjans K. Liver receptor homolog 1 is essential for PubMed Scopus Google Scholar). ovaries mice in of and were in in and ovaries were a in and to a on were in to in by in concentrations and for 1 h The granulosa cell was from follicles in ovaries from in and stages of the estrous the CL were from ovaries during was ovarian structures of ovary were obtained for by of in structures in the ovary were for protein following was from tissues as of was from the a and the of was to treatment and The was in a conducted in and of a and for a final of were to of and were to a to the and The and of for SCARB1 were and S.L. capacity of ovarian tissue in Reprod. 2009; PubMed Scopus Google Scholar), in a final of The protein was for the of SCARB1 The for and were A. L. M. B. and infertility in mice with of in Reprod. PubMed Scopus Google Scholar), in a final of the of of of a pool was of from The pool was in from to and were the described of of was the C. of PubMed Scopus Google Scholar), and the of of the was obtained from the from the of the and and were from was in and by for and SCARB1. of SCARB1 was by the by the of as described by for relative in Res. 2001; PubMed Scopus Google Scholar). The relative of SCARB1 was by the from the of Sci. 1998; PubMed Scopus Google Scholar). The independent was of the estrous structures of the ovary were obtained for protein by of in were and an of the of to were to a The membrane was in for 1 h with SCARB1 in and in in for 1 h were by were in as above, and with in for The density of the for SCARB1 and were quantified by the and in The of SCARB1 and was obtained for and by as described determine the of ovaries were following from free from tissues a in and in and of SCARB1 was by of ovaries were in for and to were in for with SCARB1 HMGR in a some were with in the of were with in for 1 h were and were with in for were in of SCARB1 was by the and of and were for of and a laser of and were for The was for high of of were for cell type theca, granulosa, the within the the was for determine the expression of SCARB1 that luteinization depends on ovulation, immature female mice of chorionic gonadotropin to follicular development, by human chorionic gonadotropin h to h to the prostaglandin to ovulation M.S. on in female luteinizing a Full Text Full Text PDF PubMed Scopus Google Scholar). and were h after the and by and the ovary of mouse were in of ovarian structures and presence of oocytes in were by in tissue and of SCARB1 was by and The ovary of mouse was in and and was that for the of 1 was to treatment and The relative of SCARB1 was by the from of Sci. 1998; PubMed Scopus Google Scholar). were treatment after and the treatment by Given the of SCARB1 in ovarian a SCARB1−/− mouse by M. Krieger (11.Trigatti B. Rayburn H. Vinals M. Braun A. Miettinen H. Penman M. Hertz M. Schrenzel M. Amigo L. Rigotti A. et al.Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology.Proc. Natl. Acad. Sci. USA. 1999; 96: 9322-9327Crossref PubMed Scopus (445) Google Scholar) was to the of SCARB1 absence on ovarian and ovulation of follicles in wild-type and SCARB1−/− mice were with and h supply was further by with de novo synthesis and of cholesterol from h to were to a combination of mevinolin an inhibitor of reductase and of chloroquine a that with cholesterol from of cholesterol from LDL C. de B. A. P. PubMed Scopus Google Scholar, H. Scavenger class type of cholesterol by high density low density and Biol. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). The the form of a and were h after the the in for 24 h and in as described of ovarian structures was by both in and tissue cholesterol ovarian and of SCARB1 in mice, SCARB1 was by as described for cholesterol was to expression of cholesterol ovarian and of HMGR was in by The was similar to that described for of that a in and a in were concentrations in serum were in a according to a described (15.Duggavathi R. Volle D.H. Mataki C. Antal M.C. Messaddeq N. Auwerx J. Murphy B.D. Schoonjans K. Liver receptor homolog 1 is essential for PubMed Scopus Google Scholar). The of was from to of progesterone were by the from of Sci. 1998; PubMed Scopus Google Scholar). were treatment and the by treatment revealed expression SCARB1 in theca, granulosa, and luteal cells In cell expression was the cytoplasm and membrane but from the was in the cytoplasm of luteal cells, and the of cytoplasm with to follicular cells, it was that SCARB1 protein expression cell is in the cells of the SCARB1 expression to be similar as follicles from to and expression increased following luteinization was in laser ovarian tissue stages of the estrous SCARB1 mRNA relative increased as from to the SCARB1 protein as by a similar of increase of SCARB1 mRNA and protein in ovarian cells by laser microdissection from ovaries stages of the estrous cycle from mice, as determined by and scavenger further the expression patterns of SCARB1 and determine the of ovulation in the increase of the SCARB1 gene expression and we treated mice with the inhibitor of with of the ovaries revealed that ovulation had in but a large follicles in the by h after treatment. The CL formation was in 24 and h In the ovaries of mice treated with oocytes by of cumulus cells in follicles and corpora h after follicles with entrapped oocytes and a corpora 24 and oocytes entrapped in follicles with h In the mice, the granulosa h after in follicles of SCARB1 mRNA increased after and was a maximum h of of treatment treatment by that ovulation with ovary SCARB1 SCARB1 protein that treatment a of the SCARB1 among ovarian In the ovaries of mice, the for SCARB1 was found in the cytoplasm of granulosa cells h after the ovulatory stimulus and to vary 24 h h The granulosa cells expression levels from In in luteal cells in corpora lutea, by the absence of an of the granulosa cell and increased relative to granulosa to increase In ovaries from in which ovulation was with the of increased expression of SCARB1 in as by h the cells in the granulosa an increase in cell and the presence of cytoplasm characteristic of luteal The SCARB1 expression was with luteinization, in of the absence of ovulation and of the In the follicles that in mice, the was similar to that in granulosa cells of the 24 h the luteal was in but it to be relative to the in that was an expression of SCARB1 expression of SCARB1 in corpora and in follicles of immature mice with and and h 24 h after Mice meloxicam, a prostaglandin synthase-2 inhibitor of of SCARB1 and of of by chorionic human chorionic scavenger that is luteal in mice bearing null mutation of the SCARB1 In we found that circulating progesterone levels in serum of mice were in SCARB1 knockout mice by 50% with the during the luteal It was of interest to determine are in ovaries of SCARB1−/− mice to progesterone The ovaries in the SCARB1−/− mice examined structures found in The was a blood-filled follicular was in of the SCARB1−/− h after and h after ovulation, ovaries from SCARB1−/− mice some normal corpora and luteinized was the presence of structures that to with the cells and the the granulosa cell of a normal follicle further this ovarian were with to revealed an membrane the and to the that this is an follicle with a hypertrophied theca to further the cholesterol pool in SCARB1−/− and mice by de novo synthesis with and LDL processing with this treatment circulating progesterone was in mice and in SCARB1−/− effect of the treatment on luteal morphology was in ovaries from the SCARB1−/− mice further the means by which SCARB1−/− mice for the in HDL we examined the of for a in the cholesterol in the luteal in and SCARB1−/− mice by and The of that HDL in SCARB1−/− mice results in increased expression of this Blockade of HMGR and with LDL metabolism had effect on the of the HMGR cellular protein in the mice. In the expression of the cholesterol in the SCARB1−/− mice. further the that increased HMGR expression is a major by which SCARB1−/− mice the cholesterol required for luteal steroid of the in cholesterol synthesis, in corpora from SCARB1−/− mature mice with and and h after Mice a combination of mevinolin an HMGR and chloroquine an inhibitor of lysosomal processing of for the SCARB1 the was chorionic human chorionic 3-hydroxy-3-methylglutaryl CoA scavenger The of expression of SCARB1 in the mouse follicle from the pig (9.Miranda-Jimenez L. Murphy B.D. Lipoprotein receptor expression during luteinization of the ovarian follicle.Am. J. Physiol. Endocrinol. Metab. 2007; 293: E1053-E1061Crossref PubMed Scopus (16) Google Scholar), the species it has been examined in in that is in the granulosa cells the estrous The protein was found in the cytoplasm and the periphery of both granulosa and luteal cells in the expression in granulosa cells is in to the pig was a low level of expression in the cytoplasm and a of the protein (9.Miranda-Jimenez L. Murphy B.D. Lipoprotein receptor expression during luteinization of the ovarian follicle.Am. J. Physiol. Endocrinol. Metab. 2007; 293: E1053-E1061Crossref PubMed Scopus (16) Google Scholar). may in in the of in demonstrated SCARB1 to be on the membrane of the revealed both and membrane Schwarz M. Rigotti A. Krieger M. of intestinal scavenger receptor class type (SR-BI) expression in rodents of bile to the J. 2001; PubMed Scopus (59) Google Scholar). further SCARB1 expression in the cumulus of the with the that the cumulus as an source of cholesterol for the K. K. regulation of mouse cumulus cells and and cholesterol in cumulus PubMed Scopus Google Scholar). The of the protein SCARB1 may an in uptake of HDL from the follicular and to the The SCARB1−/− mouse, of ovulation, is to that (12.Miettinen H.E. Rayburn H. Krieger M. Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)-deficient mice.J. Clin. Invest. 2001; 108: 1717-1722Crossref PubMed Scopus (152) Google Scholar). infertility is by of the ovaries to the (12.Miettinen H.E. Rayburn H. Krieger M. Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)-deficient mice.J. Clin. Invest. 2001; 108: 1717-1722Crossref PubMed Scopus (152) Google Scholar) by induction of hepatic SCARB1 expression in the liver (13.Yesilaltay A. Morales M.G. Amigo L. Zanlungo S. Rigotti A. Karackattu S.L. Donahee M.H. Kozarsky K.F. Krieger M. Effects of hepatic expression of the high-density lipoprotein receptor SR-BI on lipoprotein metabolism and female fertility.Endocrinology. 2006; 147: 1577-1588Crossref PubMed Scopus (55) Google Scholar). are with the that and transfer of HDL cholesterol the cumulus cells and the normal development, the the of ovulation and luteinization in SCARB1 we a pharmacological blockade of an known to be for the ovulatory process that the for Endocrinol. PubMed Scopus Google Scholar). The results that the process of SCARB1 expression in the ovary in the absence of ovulation and on a similar of SCARB1 expression in to were similar is intriguing are the ovarian structures with SCARB1 and were in a in mice in to a of the SCARB1 by treatment. the SCARB1 in follicles in the the that the granulosa cells The follicles that following treatment in expression of suggesting in a the treatment the absence of the SCARB1 protein in the SCARB1−/− In to that in ovarian morphology null and mice and in circulating progesterone (11.Trigatti B. Rayburn H. Vinals M. Braun A. Miettinen H. Penman M. Hertz M. Schrenzel M. Amigo L. Rigotti A. et al.Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology.Proc. Natl. Acad. Sci. USA. 1999; 96: 9322-9327Crossref PubMed Scopus (445) Google Scholar), pathology in the SCARB1−/− mouse corpora were in in There were large follicles that structures in mice with null mutation of the gene J.F. in reproductive tissues of female receptor null N. Y. Acad. Sci. 2001; PubMed Scopus Google Scholar), suggesting that may a in the The may be in the steroidogenic It is known that progesterone is required for ovulation V. M. gene expression in primary mouse granulosa cell Reprod. PubMed Scopus Google Scholar), and it is possible that the absence of granulosa cell steroidogenesis that after the ovulatory further by an granulosa by a hypertrophied theca, was in the ovaries of the SCARB1−/− The for this is unclear, but follicles with similar morphology can be found in a mouse to the luteinizing and are luteinizing in mice causes and ovarian PubMed Scopus Google Scholar). Given the of SCARB1 in S. Azhar S. Menon K.M. Lipoprotein of ovarian cell relative contribution of scavenger receptor class B and in high-density transport and PubMed Scopus Google Scholar), the cells produce only low levels of examined the of the of cholesterol by of de novo synthesis and with processing of treatment had effect on the morphology of the and but circulating progesterone in both and SCARB1−/− mice. The increased expression of HMGR in the SCARB1−/− ovary was to be an to the in cholesterol in the ovaries N. Schoonjans K. Murphy B.D. supply and of the gene in steroidogenic Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). The mouse bearing mutation in the gene is to process LDL cholesterol but circulating progesterone concentrations that from mice N. N. M. Murphy B.D. protein is expressed in steroidogenic tissues and by PubMed Scopus (16) Google Scholar). The of the LDL pathway is by de novo synthesis of cholesterol and importation via SCARB1. were believed to been in the it be concluded that cholesterol in the CL in the form of esters was the source of the substrate for progesterone synthesis. The for cholesterol homeostasis is by the of the active form of protein N. Schoonjans K. Murphy B.D. supply and of the gene in steroidogenic Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). of is the HMGR and evidence from the that expression is in the SCARB1−/− mouse with the that of an as in the mouse, is by increased de novo cholesterol synthesis. an expression of HMGR was of both the HDL and LDL It that increased HMGR expression is a major to supply cholesterol for luteal steroidogenesis. shown an SCARB1 protein expression in theca and granulosa cells in the mouse ovary during the final stages of follicle with expression as follicular cells in to the ovulatory of a functional SCARB1 protein resulted in of follicular structures in the ovary and in progesterone synthesis. cholesterol mechanisms can in the for a cholesterol The and for and for with and Krieger and for contribution of SCARB1 mice. corpus luteum chorionic gonadotropin human chorionic gonadotropin 3-hydroxy-3-methylglutaryl CoA reductase LDL receptor prostaglandin synthase-2 scavenger receptor-B1

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