Stimulation of progesterone production in human granulosa-lutein cells by lipoproteins: evidence for cholesterol-independent actions of high-density lipoproteins

Ragoobir, Jennifer; Abayasekara, D R E; Bruckdorfer, K. Richard; Michael, A E

doi:10.1677/joe.0.1730103

Cited by 9 publications

(6 citation statements)

References 58 publications

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“…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.…”

Section: Discussionsupporting

confidence: 92%

“…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.…”

Section: Discussionmentioning

confidence: 58%

“…Thecal vascularization and vascular permeability increase during preovulatory development, and preovulatory follicles have been reported to contain LDL and high density lipoprotein (HDL) (Simpson et al 1980, Volpe et al 1991, Jaspard et al 1997). 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).…”

Section: Introductionmentioning

confidence: 99%

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

Löhrke¹,

Viergutz²,

Krüger³

2005

Journal of Molecular Endocrinology

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The role of endogenously oxidized low density lipoprotein (oxLDL) in follicular steroidogenic regulation is unknown. Information may be important in order to elucidate ovulatory dysregulation in disordered lipid metabolism. To obtain specific data, we studied the effect of polar phospholipids (PL) isolated from oxLDL with different endogenous levels of lipohydroperoxides (LHP) on the thecal expression of mRNA encoding steroidogenic enzymes and cyclooxygenase 2 (COX-2), and on the thecal production of superoxide and progesterone. Large (preovulatory) bovine follicles were used and analyses of thecal fragments from single follicles were performed by radioimmunoassays, chemiluminescence assays and quantitative RT-PCR. Basal concentration of mRNA for several lipoprotein receptors exceeded by about 10-times the basal level of mRNA encoding steroidogenic enzymes, suggesting that preovulatory theca receptors may favour uptake of oxLDL. PL (5-11 pmol phosphorus/ml) decreased (up to 0·5-times the control) progesterone synthesis, production of superoxide and levels of P450 cholesterol side chain cleavage (P450 scc), 3 -hydroxysteroid dehydrogenase and COX-2 mRNA. Abundance of COX-2 transcripts in thecal tissue incubated with forskolin depended on the progesterone/17 -oestradiol ratio of the follicle fluid, i.e. the previous microenvironment in vivo. PL effects were mimicked by the platelet-activating factor (PAF). WEB 2086, a PAF receptor blocker, did not always abolish these responses, suggesting that the effects were not mediated solely by this receptor. PAF interfered dose-dependently with LH-induced responses, indicating interference with LH signalling. PL from mildly oxidized LDL (0·5 nmol/ml LHP) tended to exert greater effects than PL from oxLDL containing 1·5 nmol/ml LHP. In consideration of the known physiologic role of progesterone, COX-2 and possibly superoxide, these results provide evidence for a potential of PL from oxLDL to induce ovulatory dysregulation and suggest that the extent of the LDL oxidation seems to be important for interfering with thecal responses to the preovulatory LH surge.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Löhrke¹,

Viergutz²,

Krüger³

2005

Journal of Molecular Endocrinology

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“…Because P-HDL was reported to stimulate progesterone synthesis in granulosa lutein cells in vitro [18,19], we further explored the possibility that FF-HDL regulates progesterone synthesis via its S1P content. As shown in Figure 1, D and E, incubation of serum-starved hGCs and HGL5 cells with FF-HDL led to time-and dose-dependent stimulation of progesterone release, with the largest increase observed between 1.2 and 1.6 g/ml of FF-HDL.…”

Section: Ff-hdl and S1p Induce Migration Of Hgcsmentioning

confidence: 99%

Follicular Fluid High-Density Lipoprotein-Associated Sphingosine 1-Phosphate (S1P) Promotes Human Granulosa Lutein Cell Migration via S1P Receptor Type 3 and Small G-Protein RAC11

Becker¹,

Otte²,

Robenek³

et al. 2011

Biology of Reproduction

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Coordinated migration and progesterone production by granulosa cells is critical to the development of the corpus luteum, but the underlying mechanisms remain obscure. Sphingosine 1-phosphate (S1P), which is associated with follicular fluid high-density lipoprotein (FF-HDL), was previously shown to regulate ovarian angiogenesis. We herein examined the effects of S1P and FF-HDL on the function of granulosa lutein cells. Both FF-HDL and S1P induced migration of primary human granulosa lutein cells (hGCs) and the granulosa lutein cell line HGL5. In addition, FF-HDL but not S1P promoted progesterone synthesis, and neither of the two compounds stimulated proliferation of granulosa lutein cells. Polymerase chain reaction and Western blot experiments demonstrated the expression of S1P receptor type 1 (S1PR1), S1PR2, S1PR3, and S1PR5 but not S1PR4 in hGCs and HGL5 cells. The FF-HDL- and S1P-induced granulosa lutein cell migration was emulated by FTY720, an agonist of S1PR1, S1PR3, S1PR4, and S1PR5, and by VPC24191, an agonist of S1PR1 and S1PR3, but not by SEW2871 and phytosphingosine 1-phosphate, agonists of S1PR1 and S1PR4, respectively. In addition, blockade of S1PR3 with CAY1044, suramine, or pertussis toxin inhibited hGC and HGL5 cell migration toward FF-HDL or S1P, while blockade of S1PR1 and S1PR2 with W146 and JTE013, respectively, had no effect. Both FF-HDL and S1P triggered activation of small G-protein RAC1 and actin polymerization in granulosa cells, and RAC1 inhibition with Clostridium difficile toxin B or NSC23766 abolished FF-HDL- and S1P-induced migration. The FF-HDL-associated S1P promotes granulosa lutein cell migration via S1PR3 and RAC1 activation. This may represent a novel mechanism contributing to the development of the corpus luteum.

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“…Controlled ovarian hyperstimulation was induced by the sequential administration of a gonadotrophin-releasing hormone (GnRH) analogue, human menopausal gonadotrophin (hMG) and hCG as previously described (Ragoobir et al 2002). All samples were obtained with informed patient consent (in accordance with the Declaration of Helsinki) and with the approval of the local ethics committee.…”

Section: Cell Isolation and Culturementioning

confidence: 99%

Expression of 11beta-hydroxysteroid dehydrogenase (11betaHSD) proteins in luteinizing human granulosa-lutein cells

Thurston¹,

Chin

Jonas

et al. 2003

Journal of Endocrinology

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In a range of tissues, cortisol is inter-converted with cortisone by 11 -hydroxysteroid dehydrogenase (11 HSD). To date, two isoforms of 11 HSD have been cloned. Previous studies have shown that human granulosa cells express type 2 11 HSD mRNA during the follicular phase of the ovarian cycle, switching to type 1 11 HSD mRNA expression as luteinization occurs. However, it is not known whether protein expression, and 11 HSD enzyme activities reflect this reported pattern of mRNA expression. Hence, the aims of the current study were to investigate the expression and activities of 11 HSD proteins in luteinizing human granulosa-lutein (hGL) cells. Luteinizing hGL cells were cultured for up to 3 days with enzyme activities (11 -dehydrogenase (11 DH) and 11-ketosteroid reductase (11 KSR)) and protein expression (type 1 and type 2 11 HSD) assessed on each day of culture. In Western blots, an immunopurified type 1 11 HSD antibody recognized a band of 38 kDa in hGL cells and in human embryonic kidney (HEK) cells stably transfected with human type 1 11 HSD. The type 2 11 HSD antibody recognized a band of 48 kDa in HEK cells transfected with human type 2 11 HSD cDNA but the type 2 protein was not expressed in hGL cells throughout the 3 days of culture. While the expression of type 1 11 HSD protein increased progressively by 2·7-fold over 3 days as hGL cells luteinized, both 11 DH and reductase activities declined (by 52·9% and 34·2%; P,0·05) over this same period. Changes in enzyme expression and activity were unaffected by the suppression of ovarian steroid synthesis.

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Stimulation of progesterone production in human granulosa-lutein cells by lipoproteins: evidence for cholesterol-independent actions of high-density lipoproteins

Cited by 9 publications

References 58 publications

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

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

Follicular Fluid High-Density Lipoprotein-Associated Sphingosine 1-Phosphate (S1P) Promotes Human Granulosa Lutein Cell Migration via S1P Receptor Type 3 and Small G-Protein RAC11

Expression of 11beta-hydroxysteroid dehydrogenase (11betaHSD) proteins in luteinizing human granulosa-lutein cells

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