Direct effect of arachidonic acid on protein kinase C and LH-stimulated steroidogenesis in rat Leydig cells; evidence for tonic inhibitory control of steroidogenesis by protein kinase C.

López-Ruiz, M.P.; Choi, Michael S.K.; Rose, Matthew P.; West, Anthony P.; Cooke, Brian A.

doi:10.1210/endo.130.3.1311229

Cited by 26 publications

(25 citation statements)

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“…PKC has important roles in various biological processes (e.g., signal transduction, cell proliferation) including the tonic inhibitor control of steroidogenesis as reported in mammal cells stimulated by intracellular ARA [15,16,53]. In this study, results do not indicate that PKC was involved in maintaining similar cortisol levels between groups.…”

Section: Discussioncontrasting

confidence: 67%

Dietary Lecithin Source Affects Growth Potential and Gene Expression in Sparus aurata Larvae

Martins

Estévez

Stickland

et al. 2010

Lipids

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Soybean lecithin (SBL), used as a phospholipid source in larval fish diets, may compromise growth and survival in marine species, and affect gene expression, due to differences in fatty acid composition relative to marine lecithins (ML). The potential of SBL as a phospholipid source in gilthead seabream microdiets as compared to ML was evaluated. Two stocking densities were tested in order to exacerbate possible dietary effects: 5 and 20 larvae L(-1). Larvae reflected dietary fatty acid profiles: linoleic acid was higher, whereas eicosapentaenoic and arachidonic acids were lower in SBL fed groups than in ML fed larvae. Highest stocking density decreased survival, and led to elevated saturates and lower docosahexaenoic acid levels in polar lipid. Muscle histology observations showed hindered growth potential in SBL fed larvae. Despite similar cortisol levels between treatments, higher glucocorticoid receptor (GR), as well as hormone-sensitive lipase (HSL) mRNA levels in SBL fed groups revealed a role for fatty acids in gene regulation. Further analysed genes suggested these effects were independent from the hypothalamus-pituitary-interrenal axis control and the endocannabinoid system. Cyclooxygenase-2 and gluconeogenesis seemed unaffected. For the first time in fish, a link between dietary lecithin nature and HSL gene transcription, perhaps regulated through GR fatty acid-induced activation, is suggested. Enhanced lipolytic activity could partly explain lower growth in marine fish larvae when dietary ML is not provided.

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Section: Discussioncontrasting

confidence: 67%

Dietary Lecithin Source Affects Growth Potential and Gene Expression in Sparus aurata Larvae

Martins

Estévez

Stickland

et al. 2010

Lipids

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“…The involvement of the PKC pathway in Leydig cell steroidogenesis has been documented, and the mechanisms that regulate steroidogenesis and StAR expression via PKC action appear to be highly dependent on the cells and their tissue types, as well as the external stimuli influencing these cells. Several studies have shown that the PKC pathway is involved in the activation of steroid synthesis [31,34,57], while others have observed negative relationships [31,34,35,[58][59][60] or no effect [61] in various cell types. It appears that the concentration of PMA is one critical factor in controlling trophic hormone effects on steroid production.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Protein Kinase C and Cyclic Adenosine 3′,5′-Monophosphate-Dependent Kinase in Steroidogenic Acute Regulatory Protein Expression and Steroid Biosynthesis in Leydig Cells1

King

Khan

et al. 2005

Biology of Reproduction

103

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This study investigated the roles of the protein kinase C (PKC) and protein kinase A (PKA) pathways in regulating constitutive steroidogenesis and steroidogenic acute regulatory (STAR; herein designated by its common name, StAR) protein in R2C Leydig tumor cells. Inhibition of PKC and phospholipase C resulted in significant decreases in steroid production, phosphorylation of cAMP-responsive element binding (CREB) protein, and Star gene transcription under basal conditions in R2C cells. These observations were corroborated in MA-10 and mLTC-1 Leydig tumor cell lines, in which activation of PKC by phorbol-12-myristate-13-acetate (PMA, 10 nM) increased CREB phosphorylation and total StAR (tot-StAR) protein expression. However, induction of StAR protein by PMA did not result in the expected concomitant increase in steroids because PKC failed to phosphorylate StAR, the biologically active form of the protein. However, in conjunction with PMA, minor increases in PKA activity using submaximal doses of (Bu)2cAMP (0.05-0.1 mM; a concentration range insufficient for induction of StAR), were able to stimulate dramatic increases in both phospho-StAR (P-StAR) and steroid production. Human chorionic gonadotropin stimulation also resulted in a further enhancement in P-StAR and progesterone production when added to PMA-treated MA-10 cells. Similar results for tot-StAR and P-StAR expression were observed in primary cultures of immature rat Leydig cells treated with PMA and submaximal doses of (Bu)2cAMP. In summary, the present study demonstrates that basal activities of both PKC and PKA play important roles in the constitutive steroidogenic characteristics of R2C cells. This study also demonstrates for the first time a role for PMA-induced PKC in StAR protein regulation and the requirement for submaximal doses of cAMP to produce steroids in Leydig cells.

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“…Values represent the mean 6 SD of three experiments from different cultures. Different letters indicate a significant difference at P , 0.05. rated fatty acid, arachidonic acid, is able to modify STAR expression and, consequently, to regulate the cholesterol transfer to the mitochondrial inner membrane, which is the rate-limiting step of steroidogenesis in mouse Leydig cells [40][41][42]. Furthermore, the metabolites of the lipoxygenase and epoxygenase pathways have been demonstrated to stimulate HSD3B and HSD17B activities and to enhance the synthesis of testicular steroid hormones [43].…”

Section: Expression Of Scd2 In Ovarymentioning

confidence: 99%

Expression and Regulation of the SCD2 Desaturase in the Rat Ovary

Moreau

Froment²,

Tosca

et al. 2006

Biology of Reproduction

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Despite the significant role of the lipid reserve in cell structure and function, very few studies have provided detailed descriptions of unsaturated fatty acid synthesis in the ovary. In the present study, we have shown by RT-PCR, Northern blot, and Western blot analyses the mRNA and protein expression of SCD2 (stearoyl-coenzyme A desaturase 2; also named delta 9 desaturase) in rat ovary. We also have localized Scd2 mRNA by in situ hybridization, mainly in granulosa cells of antral follicles, cumulus oophorus, and corpus luteum. Interestingly, either no or very weak SCD2 expression was observed in primordial follicles and oocytes. After eCG injection for 24 h in immature rats (age, 22 days), the level of SCD2 expression and SCD activity in ovary was increased by approximately fourfold (P < 0.05), and the response was further increased 48 h after hCG treatment. As expected, eCG/hCG treatment increased expression of the steroidogenesis enzymes (CYP11A1 and HSD3B) and STAR. We also found a decrease in the SCD2 expression and SCD activity in the corpus luteum at Days 10 and 15 compared to Day 3 of gestation, paralleled by a decrease in the expression of the steroidogenesis enzymes and STAR. To investigate the molecular mechanisms involved in the regulation of SCD2 expression in ovary, we performed primary culture of rat granulosa cells. We observed that both insulin-like growth factor 1 (IGF1) (7.5 x 10(-8)g/ml) and FSH (350 x 10(-8)g/ml) increased SCD2 expression and SCD activity by approximately threefold. Using specific inhibitors, we demonstrated that the MAPK3/MAP1 and PIK3R1/AKT pathways are involved in the IGF1- and FSH-induced SCD2 expression, respectively. The SCD2 is expressed and active in rat ovary, and it may be involved in the regulation of follicular growth and/or the oocyte maturation.

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Direct effect of arachidonic acid on protein kinase C and LH-stimulated steroidogenesis in rat Leydig cells; evidence for tonic inhibitory control of steroidogenesis by protein kinase C.

Cited by 26 publications

References 0 publications

Dietary Lecithin Source Affects Growth Potential and Gene Expression in Sparus aurata Larvae

Dietary Lecithin Source Affects Growth Potential and Gene Expression in Sparus aurata Larvae

Involvement of Protein Kinase C and Cyclic Adenosine 3′,5′-Monophosphate-Dependent Kinase in Steroidogenic Acute Regulatory Protein Expression and Steroid Biosynthesis in Leydig Cells1

Expression and Regulation of the SCD2 Desaturase in the Rat Ovary

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