Arachidonic acid is involved in the regulation of HCG induced steroidogenesis in rat leydig cells

Didolkar, Ashok K.; Sundaram, K.

doi:10.1016/0024-3205(87)90223-2

Cited by 44 publications

(22 citation statements)

References 25 publications

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“…Previous studies have reported that phospholipase A 2 (PLA 2 ) inhibitors abrogate the effect of LH-and ACTH-stimulated steroid production thereby suggesting the involvement of PLA 2 in the mechanism of action of trophic hormones (2,3,7). However, no evidence has been reported demonstrating the activation of PLA 2 by steroidogenic hormones.…”

Section: Introductionmentioning

confidence: 97%

Arachidonic Acid Regulation of Steroid Synthesis: New Partners in the Signaling Pathway of Steroidogenic Hormones

et al. 2004

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Although the role of arachidonic acid (AA) in trophic hormone-stimulated steroid production in various steroidogenic cells is well documented, the mechanism responsible for AA release remains unknown. We have previously shown evidence of an alternative pathway of AA generation in steroidogenic tissues. Our results are consistent with the hypothesis that, in steroidogenic cells, AA is released by the action of a mitochondrial acyl-CoA thioesterase (MTE-I). We have shown that recombinant MTE-I hydrolyses arachidonoyl-CoA to release free AA. An acyl-CoA synthetase specific for AA, acyl-CoA synthetase 4, has also been described in steroidogenic tissues. In the present study we investigate the new concept in the regulation of intracellular levels of AA, in which trophic hormones can release AA by mechanisms different from the classical PLA2-mediated pathway. Inhibition of ACS4 and MTE-I activity by triacsin C and NDGA, respectively results in a reduction of StAR mRNA and protein abundance. When both inhibitors are added together there is a synergistic effect in the inhibition of StAR mRNA, StAR protein levels and ACTH-stimulated steroid synthesis. The inhibition of steroidogenesis produced by the NDGA and triacsin C can be overcome by the addition of exogenous AA. In summary, results shown here demonstrate a critical role of the acyl-CoA synthetase and the acyl-CoA thioesterase in the regulation of AA release, StAR induction, and steroidogenesis. This further suggests a new concept in the regulation of intracellular distribution of AA through a mechanism different from the classical PLA2-mediated pathway that involves a hormone-induced acyl-CoA synthetase and a hormone-regulated acyl-CoA thioesterase.

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Section: Introductionmentioning

confidence: 97%

Arachidonic Acid Regulation of Steroid Synthesis: New Partners in the Signaling Pathway of Steroidogenic Hormones

et al. 2004

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“…a role in testosterone formation in rat Leydig cells [49,50]. Thus, the increased AA in the present study may explain why Ppard activation confers placental endocrine system development and placentation.…”

Section: Ding Et Almentioning

confidence: 69%

Activation of Peroxisome Proliferator Activator Receptor Delta in Mouse Impacts Lipid Composition and Placental Development at Early Stage of Gestation1

Ding

Zhang

Liu³

et al. 2014

Biology of Reproduction

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Peroxisome proliferator-activated receptor delta (Ppard) activation has been implicated in regulating a multitude of biological processes in placental development. In this study, we employed the UPLC-ESI-TOFMS approach to investigate the metabolic traits in placenta from GW501516-treated mice at Embryonic Day 10.5. By analyzing the mass spectrum data, ions with the most significant differences between control and GW501516-treated groups were identified. Among these metabolites, the fatty acids, phospholipids, and sterol lipids were dramatically increased. Ingenuity Pathway Analysis (IPA) showed that phosphatidylethanolamine biosynthesis and glycolysis were the top two altered metabolic pathways involved in carbohydrate metabolism, energy production, and lipid metabolism. Subsequent immunoblotting experiments provided evidence for positive correlation of PPARD level and AKT and ERK signaling pathways upon GW501516 treatment. Furthermore, the stimulation of GW501516 increased trophoblast cell fusion gene syncytin-A (Syna), but not syncytin-B (Synb), expression, suggesting a potential role of Ppard activation in promoting cytotrophoblast differentiation. Our results reveal that Ppard activation elicits dramatic changes of the metabolic activities in placenta, which is correlated to AKT and ERK signaling.

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“…In Leydig cells, several reports have indicated that AA may regulate both basal and hormone-stimulated steroidogenesis (Didolkar & Sundaram 1987, Lopez-Ruiz et al 1992, Marinero et al 1996. This suggests a link between intracellular release of AA and steroidogenesis.…”

Section: Discussionmentioning

confidence: 97%

“…AA may be released after hormone-receptor interaction, mainly by the action of phospholipase A 2 (PLA 2 ) or phospholipase C (PLC) and diacyglycerol lipase. In addition, AA can be metabolized by three independent pathways (cyclo-oxygenase, lipoxygenase and the cytochrome P450-dependent epoxygenase; Needleman et al 1986), producing metabolites able to regulate LH and LH releasing hormone (LHRH)-induced testosterone production by rat Leydig cells (Didolkar & Sundaram 1987, Romanelli et al 1995, Mele et al 1997.…”

Section: Introductionmentioning

confidence: 99%

Arachidonic acid release from rat Leydig cells: the involvement of G protein, phospholipase A2 and regulation of cAMP production

Ronco

Moraga²,

Llanos³

2002

Journal of Endocrinology

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We have previously demonstrated that the release of arachidonic acid (AA) from human chorionic gonadotropin (hCG)-stimulated Leydig cells occurs in a dose-and time-dependent manner. In addition, the amount of AA released was dependent on the hormone-receptor interaction and the concentration of LH-hCG binding sites on the cell surface. The present study was conducted to evaluate the involvement of phospholipase A 2 (PLA 2 ) and G proteins in AA release from hormonally stimulated rat Leydig cells, and the possible role of this fatty acid in cAMP production. Cells were first prelabelled with [ 14 C]AA to incorporate the fatty acid into cell phospholipids, and then treated in different ways to evaluate AA release. hCG (25 mIU) increased the release of AA to 180 12% when compared with AA released from control cells, arbitrarily set as 100%. Mepacrine and parabromophenacyl bromide (pBpB), two PLA 2 inhibitors, decreased the hormone-stimulated AA release to 85 9 and 70 24% respectively. Conversely, melittin, a PLA 2 stimulator, increased the release of AA up to 200% over control. The inhibitory effect of mepacrine on the release of AA was evident in hCG-treated Leydig cells, but not in the melittin-treated cells. To determine if the release of AA was also mediated through a G protein, cells were first permeabilized and subsequently treated with pertussis toxin or GTP S, a non-hydrolyzable analog of GTP. Results demonstrate that GTP S was able to induce a similar level of the release of AA as hCG. In addition, pertussis toxin completely abolished the stimulatory effect of hCG on the release of AA, indicating that a member of the G i family was involved in the hCG-dependent release of AA. Cells treated with PLA 2 inhibitors did not modify cAMP production, but exogenously added AA significantly reduced cAMP production from hCG-treated Leydig cells, in a manner dependent on the concentration of AA and hCG. Results presented here suggest an involvement of PLA 2 and G proteins in the release of AA from hCG-stimulated Leydig cells, and under particular conditions, regulation of cAMP production by this fatty acid in these cells.

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Arachidonic acid is involved in the regulation of HCG induced steroidogenesis in rat leydig cells

Cited by 44 publications

References 25 publications

Arachidonic Acid Regulation of Steroid Synthesis: New Partners in the Signaling Pathway of Steroidogenic Hormones

Arachidonic Acid Regulation of Steroid Synthesis: New Partners in the Signaling Pathway of Steroidogenic Hormones

Activation of Peroxisome Proliferator Activator Receptor Delta in Mouse Impacts Lipid Composition and Placental Development at Early Stage of Gestation1

Arachidonic acid release from rat Leydig cells: the involvement of G protein, phospholipase A2 and regulation of cAMP production

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