Lipid Transport in the Developing Bovine Follicle: Messenger RNA Expression Increases for Selective Uptake Receptors and Decreases for Endocytosis Receptors

Abstract

Differences in rates of steroid production and secretion will, eventually, determine the developmental rates of ovarian follicles. The major supply of cholesterol, the precursor for steroid and androgen biosynthesis, to ovarian cells is from circulating lipoproteins via membrane receptors from the low density lipoprotein receptor (LDL) superfamily. This occurs by either endocytosis, which has been described for very low density lipoprotein receptors (VLDLr), for LDL receptors (LDLr), and by the selective uptake pathway described for the scavenger receptor class B type 1 receptor (SRB1) and the recently described ovarian receptor, lipoprotein receptor-related protein 8 (LRP8). In this study, the mRNA expression of these four cholesterol receptors in bovine ovarian cells was determined at different stages of follicular development. In small antral follicles, mRNA expression of the endocytosis receptors was higher than in large antral follicles. Expression of LRP8 mRNA increased linearly with follicular size together with an increase in LDL, VLDL, and cholesterol concentrations in the follicular fluid. SRB1 mRNA expression tended to increase with follicular diameter. Because different mRNA expression patterns were found for the two types of receptor, this may imply different regulation of cholesterol supply at different stages of follicular development. Accumulation of LDL and VLDL particles in the follicular fluid of large antral follicles may enhance cholesterol availability for the intense steroidogenic activity that is essential at these stages.

Polar phospholipids from bovine endogenously oxidized low density lipoprotein interfere with follicular thecal function

“…We observed a marked preovulatory thecal expression of transcripts encoding lipoprotein receptors. In agreement with previous studies on other ovarian cells or follicle stages (Brannian et al 1995, Ragoobir et al 2002, Argov et al 2004), these observations allow us to conclude that circulating lipoproteins appear to be an important source for preovulatory steroidogenesis. In our study, the cAMP/PKA pathway was experimentally induced by LH or the PKA-activator, forskolin, to obtain a positive control.…”

“…Inhibition of the corresponding pathways has been reported to block ovulation or to impair fertilization (Tanaka et al 1991, Behrman et al 2001, Sirois et al 2004. Various pathways regulate progesterone synthesis, including the supply of substrate mediated by several types of lipoprotein receptors and intracellular transporters (Ragoobir et al 2002, Argov et al 2004, and cAMP/PKA-and PGE 2 -signalling (Elvin et al 2000). We observed a marked preovulatory thecal expression of transcripts encoding lipoprotein receptors.…”

“…The LH surge induces an intense synthesis of progesterone in follicular thecal and granulosal layers, requiring a supply of serum lipoproteins as steroidogenic substrates in some mammalian species (Carroll et al 1992, Brannian et al 1995. Steroidogenic tissue is capable of utilizing circulating lipids via expression of diverse ligands and receptors (Umans et al 1999, Argov et al 2004. Progesterone possesses anti-mitogenic and anti-apoptotic properties that are mediated via progesterone receptors (Peluso & Pappalardo 1998, Quirk et al 2004.…”

“…These lipoproteins have been shown to support synthesis of progesterone by supplying cholesterol from LDL (Bao et al 1995) but also by cholesterol-dependent and -independent actions of HDL , Ragoobir et al 2002. Follicle cells express receptors of the LDL superfamily, including very low density lipoprotein (VLDL) receptors, LDL receptors and lipoprotein receptor-related protein (LRP) receptors (Argov et al 2004). The uptake of LDL is mediated via an endocytotic pathway (Golos et al 1986) and the 2-macroglobulin receptor (Chu & Pizzo 1994, Ireland et al 2004.…”

“…The uptake of LDL is mediated via an endocytotic pathway (Golos et al 1986) and the 2-macroglobulin receptor (Chu & Pizzo 1994, Ireland et al 2004. The uptake of lipoprotein particle remnants and HDL is mediated via the scavenger receptor, class B, type I and LRP receptors (Acton et al 1996, Argov et al 2004. While intact LDL is known to stimulate luteal steroidogenesis (Pate & Condon 1989, Brannian et al 1995, oxidatively modified LDL (oxLDL) prepared in a laboratory setting has been reported to inhibit luteal progesterone production (Carroll et al 1992).…”