Stimulatory effect of LH, PGE2 and progesterone on StAR protein, cytochrome P450 cholesterol side chain cleavage and 3β hydroxysteroid dehydrogenase gene expression in bovine luteal cells

Rękawiecki, Robert; Nowik, Marta; Kotwica, J.

doi:10.1016/j.prostaglandins.2005.06.009

Cited by 68 publications

(68 citation statements)

References 62 publications

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“…However, changes in the expression of the enzyme 20a-HSD, that catabolizes progesterone into the inactive progestin and 20a-DHP cannot be rule out. Coincident with a previous report (Rekawiecki et al 2005), the presence of progesterone in the culture medium caused an increase in CL STAR protein expression. It is worth noting that the inhibition of Notch overrides this effect, suggesting an influence of the Notch pathway on the progesterone autocrine CL regulation.…”

Section: Link Between Notch and Progesterone In CL Functionsupporting

confidence: 85%

A link between Notch and progesterone maintains the functionality of the rat corpus luteum

et al. 2015

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In this study, we investigated the interaction between the Notch pathway and progesterone to maintain the functionality of the corpus luteum (CL). When Notch signaling is activated, the g-secretase complex releases the active intracellular domains (NICD) of their receptors, which exert survival effects. We designed studies to analyze whether the in vitro inhibition of Notch affects progesterone production, steroidogenic regulators, apoptotic parameters, and signaling transduction pathways in the cultures of CL isolated from pregnant and superovulated rats. We detected a decrease in progesterone production when corpora lutea (CL) were incubated with N-(N-(3,5-difluorophenacetyl-L-alanyl))-S-phenylglycine t-butyl ester (DAPT), a g-secretase inhibitor. This effect could be in part due to the decrease detected in the CL protein levels of P450scc because STAR and 3b-hydroxysteroid dehydrogenase were not affected by Notch inhibition. Besides, the addition of aminoglutethimide to the CL culture medium decreased NICD of NOTCH1. We observed an increase in the expression of active CASPASE3 (CASP3) after inhibition by Notch, which was reversed by the presence of progesterone. The BAX:BCLX L ratio was increased in CL treated with DAPT and the presence of progesterone reversed this effect. In addition, phosphorylation of AKT was inhibited in CL treated with DAPT, but had no effect on ERK activation. To demonstrate that the action of DAPT is specifically related with the inhibition of Notch, CLs were incubated with DLL4 antibody and a decrease in progesterone production was detected. These results suggest the existence of a novel link between progesterone and the Notch signaling pathway to maintain the functionality of the CL.

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Section: Link Between Notch and Progesterone In CL Functionsupporting

confidence: 85%

A link between Notch and progesterone maintains the functionality of the rat corpus luteum

et al. 2015

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“…It was noteworthy that P 4 increased significantly 30 min after application of hCG in the control, but not in the LPS group. In cattle, LH binds to its specific receptor LHCGR and ultimately increases synthesis of STAR and activity of cytochrome P450scc and HSD3B, followed by an increase in P 4 secretion (Rekawiecki et al 2005). However, in control ovaries in the present study, mRNA expressions of LHCGR, STAR and HSD3B were not increased 30 min after hCG challenge, although P 4 concentrations were already higher at that time.…”

Section: Discussioncontrasting

confidence: 70%

“…However, in control ovaries in the present study, mRNA expressions of LHCGR, STAR and HSD3B were not increased 30 min after hCG challenge, although P 4 concentrations were already higher at that time. Consistently, concentrations of mRNA for STAR, and HSD3B (measured at 3-h intervals) were not increased until 6 h after luteal cell stimulation with LH (Rekawiecki et al 2005). Furthermore, LH responsiveness seemed to be more dependent on the extent of desensitization of luteal cells to LH (e.g., by extensive clustering and internalization of the receptor complex) than on the number of LH receptors, as during functional luteolysis, luteal cells apparently became desensitized to LH, despite maintenance of LHCGR (Amsterdam et al 2002).…”

Section: Discussionmentioning

confidence: 64%

Lipopolysaccharide enhances apoptosis of corpus luteum in isolated perfused bovine ovaries in vitro

Lüttgenau¹,

Möller²,

Kradolfer³

et al. 2016

Reproduction

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Lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria, has detrimental effects on the structure and function of bovine corpus luteum (CL) in vivo. The objective was to investigate whether these effects were mediated directly by LPS or via LPS-induced release of PGF 2a . Bovine ovaries with a mid-cycle CL were collected immediately after slaughter and isolated perfused for 240 min. After 60 min of equilibration, LPS (0.5 mg/ml) was added to the medium of five ovaries, whereas an additional six ovaries were not treated with LPS (control). After 210 min of perfusion, all ovaries were treated with 500 iu of hCG. In the effluent perfusate, concentrations of progesterone (P 4 ) and PGF 2a were measured every 10 and 30 min, respectively. Punch biopsies of the CL were collected every 60 min and used for RT-qPCR to evaluate mRNA expression of receptors for LPS (TLR2, -4) and LH (LHCGR); the cytokine TNFA; steroidogenic (STAR, HSD3B), angiogenic (VEGFA 121 , FGF2), and vasoactive (EDN1) factors; and factors of prostaglandin synthesis (PGES, PGFS, PTGFR) and apoptosis (CASP3, -8, -9). Treatment with LPS abolished the hCG-induced increase in P 4 (P%0.05); however, there was a tendency (PZ0.10) for increased release of PGF 2a at 70 min after LPS challenge. Furthermore, mRNA abundance of TLR2, TNFA, CASP3, CASP8, PGES, PGFS, and VEGFA 121 increased (P%0.05) after LPS treatment, whereas all other factors remained unchanged (PO0.05).In conclusion, reduced P 4 responsiveness to hCG in LPS-treated ovaries in vitro was not due to reduced steroidogenesis, but was attributed to enhanced apoptosis. However, an impact of luteal PGF 2a could not be excluded.

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“…Progesterone is one of the fundamental steroid hormones for the regulation of the bovine estrous cycle, and its biosynthesis is attributed to the increased expression of steroidogenic acute regulatory protein (Star) and cytochrome P-450 (CYP11A1) (Mosa et al 2015;Zhang et al 2015). The mechanism of progesterone biosynthesis involves CYP11A1 catalyzing the conversion of cholesterol to pregnenolone and Star transporting cholesterol from the outer to the inner mitochondrial membrane (Pescador et al 1996;Rekawiecki et al 2005). In this study, we found that the mRNA expression of CYP11A1 and Star decreased, but the P 4 level has no significant difference between control and heat treatment group.…”

Section: Discussionmentioning

confidence: 99%

The effect of heat stress on gene expression, synthesis of steroids, and apoptosis in bovine granulosa cells

Luo

et al. 2016

Cell Stress and Chaperones

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Summer heat stress (HS) is a major contributing factor in low fertility in lactating dairy cows in hot environments. Heat stress inhibits ovarian follicular development leading to diminished reproductive efficiency of dairy cows during summer. Ovarian follicle development is a complex process. During follicle development, granulosa cells (GCs) replicate, secrete hormones, and support the growth of the oocyte. To obtain an overview of the effects of heat stress on GCs, digital gene expression profiling was employed to screen and identify differentially expressed genes (DEGs; false discovery rate (FDR) ≤ 0.001, fold change ≥2) of cultured GCs during heat stress. A total of 1211 DEGs including 175 upregulated and 1036 downregulated ones were identified, of which DEGs can be classified into Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results suggested that heat stress triggers a dramatic and complex program of altered gene expression in GCs. We hypothesized that heat stress could induce the apoptosis and dysfunction of GCs. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of steroidogenic genes (steroidogenic acute regulatory protein (Star), cytochrome P-450 (CYP11A1), CYP19A1, and steroidogenic factor 1 (SF-1)) and apoptosis-related genes (caspase-3, BCL-2, and BAX). Radio immunoassay (RIA) was used to analyze the level of 17β-estradiol (E 2 ) and progesterone (P 4 ). We also assessed the apoptosis of GCs by flow cytometry. Our data suggested that heat stress induced GC apoptosis through the BAX/BCL-2 pathway and reduced the steroidogenic gene messenger RNA (mRNA) expression and E 2 synthesis. These results suggest that the decreased function of GCs may cause ovarian dysfunction and offer an improved understanding of the molecular mechanism responsible for the low fertility in cattle in summer.

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Stimulatory effect of LH, PGE2 and progesterone on StAR protein, cytochrome P450 cholesterol side chain cleavage and 3β hydroxysteroid dehydrogenase gene expression in bovine luteal cells

Cited by 68 publications

References 62 publications

A link between Notch and progesterone maintains the functionality of the rat corpus luteum

A link between Notch and progesterone maintains the functionality of the rat corpus luteum

Lipopolysaccharide enhances apoptosis of corpus luteum in isolated perfused bovine ovaries in vitro

The effect of heat stress on gene expression, synthesis of steroids, and apoptosis in bovine granulosa cells

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