Scavenger receptor-B1 and luteal function in mice

Abstract

This article is available online at http://www.jlr.org augmentation of the supply is by importation of lipoprotein-bound cholesterol ( 1 ). Low-density lipoproteins enter cells by receptor-mediated endocytosis of the LDL complex and the LDL receptor (LDLR) ( 2 ). 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 ). 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 ). 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 ). The HDL pathway appears to predominate in the CL of rodents ( 1 ), and SCARB1 is expressed in theca and luteal cells of the rat ovary ( 6 ). 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 ). There is a low level of expression of SCARB1 in mouse granulosa cells ( 8 ), and recent studies of luteinization in the pig demonstrated similar low expression of SCARB1 in the granulosa cells of the follicle ( 9 ). 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 ). 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 Abstract

Expression and regulation of scavenger receptor class B type 1 in the rat ovary and uterus during the estrous cycle

“…SR-B1 expression is essential for maintaining normal ovarian cholesterol homeostasis and luteal steroid synthesis (Jimenez et al, 2010;Miranda-Jimenez and Murphy, 2007). Data in this study showed that SR-B1 expression in the ovary grew up during proestrus and estrus.…”

“…Besides, SR-B1 mRNA expression reached its highest level at metoestrus in the new CL then gradually declined; while in the old CL, it was consistently high throughout the estrous cycle (Taketa et al, 2012). Moreover, SR-B1 expression appeared to be similar as follicles developed from proestrus to estrus, and expression increased drastically following luteinization in mice (Jimenez et al, 2010). Our results demonstrated that the expression levels of SR-B1 mRNA and protein were consistent and were highest during metoestrus and lowest during diestrus in the ovary.…”

“…Data in this study showed that SR-B1 expression in the ovary grew up during proestrus and estrus. As luteinization formed during metoestrus, the abundant SR-B1 expression in the corpus luteum correlated with luteinization in vivo (Jimenez et al, 2010;Li et al, 1998), which could increase seven-fold during bovine luteinization (Rajapaksha et al, 1997). In the normal estrous cycle (non-fertile), rat corpus luteum (CL) would undergo formation and degeneration during metoestrus and diestrus, respectively.…”

“…During the early phase of follicle maturation, the major steroidogenic cell types were the thecal and interstitial cells, which played crucial roles in controlling follicular growth and atresia, regulating ovarian steroidogenesis and providing supporting structural framework for ovarian follicles (Parrott and Skinner, 1998). In the mouse, SR-B1 is expressed in cytoplasm and periphery of theca, granulosa, and cumulus cells of developing follicles and increases dramatically during formation of corpora lutea (Jimenez et al, 2010). Like other steroidogenic cells, thecal and interstitial cells required extraneous cholesterol for the initial step in the steroidogenic process, in which, SR-B1 supplied cholesterol for synthesis of androgen steroids that served as substrates for estrogen production (Li et al, 2001;Wu et al, 2003).…”

“…SR-B1 gene knockout (KO) mice were accompanied by abnormal structure, composition, and abundance of lipoproteins, which altered the development of female gametes and caused a significant proportion of ovulated oocytes to die soon after ovulation, resulting in infertility (Trigatti et al, 1999). More recently, Jimenez reported that SR-B1 KO mice had 50% lower serum progesterone levels than normal wild-type mice (Jimenez et al, 2010), and markedly lower progesterone secretion was associated with SR-B1 protein deficiency in human granulosa cells (Kolmakova et al, 2010).…”