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.

doi:10.1210/en.130.3.1122

Cited by 29 publications

(13 citation statements)

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“…However, the results from these two inhibitors were essentially identical and thus corroborated our earlier observations. Since StAR protein was demonstrated to play a critical role in cholesterol transfer to the mitochondrial inner membrane (1-4), these results are in agreement with the earlier experiments that suggested that AA regulates steroidogenesis at the rate-limiting step of mitochondrial cholesterol transfer (14,15).…”

Section: Discussionsupporting

confidence: 87%

“…Since previous studies suggested that AA and its metabolites act at the ratelimiting step of steroid biosynthesis, cholesterol transfer to the inner mitochondrial membrane (14,15), we reasoned that the StAR protein might be involved in the role of AA in the regulation of steroidogenesis. This hypothesis was proven correct by our recent studies, which indicated that AA release is essential for StAR protein expression (16).…”

mentioning

confidence: 99%

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The Role of Arachidonic Acid in Steroidogenesis and Steroidogenic Acute Regulatory (StAR) Gene and Protein Expression

Wang

Walsh

Reinhart

et al. 2000

Journal of Biological Chemistry

148

101

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Section: Discussionsupporting

confidence: 87%

mentioning

confidence: 99%

The Role of Arachidonic Acid in Steroidogenesis and Steroidogenic Acute Regulatory (StAR) Gene and Protein Expression

Wang

Walsh

Reinhart

et al. 2000

Journal of Biological Chemistry

148

101

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“…Conversely, melittin, the activator of PLA 2 , had positive effects on testosterone production (Mukhopadhyay et al 1985). Although these results provide evidence for a stimulatory role of AA on steroidogenesis, it was also shown that exogenous AA might exert a dose-and time-dependent biphasic effect on LHstimulated Leydig cells (Lopez-Ruiz et al 1992). In cells incubated with sub-maximal LH concentrations, AA did not modify testosterone production.…”

Section: Discussionmentioning

confidence: 76%

“…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: 98%

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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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24R,25-(OH)2D3 mediates its membrane receptor-dependent effects on protein kinase C and alkaline phosphatase via phospholipase A2 and cyclooxygenase-1 but not cyclooxygenase-2 in growth plate chondrocytes

Schwartz¹,

Sylvia

Toro

et al. 2000

J. Cell. Phys.

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Recent studies have shown that 24R,25-(OH)(2)D(3) mediates its effects on growth plate chondrocytes via membrane receptors. This study examined the roles of phospholipase A(2) (PLA(2)) and cyclooxygenase (Cox) in the mechanism of action of 24R, 25-(OH)(2)D(3) in resting zone chondrocytes in order to determine whether the activity of one or both enzymes provides a regulatory checkpoint in the signaling pathway resulting in increased protein kinase C (PKC) activity. We also determined whether constitutive or inducible Cox is involved. Cultures were incubated with 24R, 25-(OH)(2)D(3) for 90 min to measure PKC or for 24 h to measure physiological responses ([(3)H]-thymidine incorporation, alkaline phosphatase-specific activity, [(35)S]-sulfate incorporation). Based on RT-PCR and Northern blot analysis, resting zone chondrocytes express mRNAs for both Cox-1 and Cox-2. Levels of mRNA for both proteins were unchanged from control levels after a 24-h incubation with 24R,25-(OH)(2)D(3). To examine the role of Cox, the cultures were also treated with resveratrol (a specific inhibitor of Cox-1), NS-398 (a specific inhibitor of Cox-2), or indomethacin (a general Cox inhibitor). Cox-1 inhibition resulted in effects on proliferation, differentiation, and matrix production typical of 24R, 25-(OH)(2)D(3). In contrast, inhibition of Cox-2 had no effect, indicating that 24R,25-(OH)(2)D(3) exerts its effects via Cox-1. Inhibition of Cox-1 also blocked 24R,25-(OH)(2)D(3)-dependent increases in PKC. Activation of PLA(2) with melittin inhibited 24R, 25-(OH)(2)D(3)-dependent stimulation of PKC, and inhibition of PLA(2) with quinacrine stimulated PKC in response to 24R, 25-(OH)(2)D(3). Inclusion of resveratrol reduced the melittin-dependent inhibition of PLA(2) and caused an increase in quinacrine-stimulated PLA(2) activity. Metabolism of arachidonic acid to leukotrienes is not involved in the response to 24R, 25-(OH)(2)D(3) because inhibition of lipoxygenase had no effect. The effect of 24R,25-(OH)(2)D(3) was specific because 24S,25-(OH)(2)D(3), the biologically inactive stereoisomer, failed to elicit a response from the cells. These results support the hypothesis that 24R, 25-(OH)(2)D(3) exerts its effects via more than one signaling pathway and that these pathways are interrelated via the modulation of PLA(2). PKC regulation may occur at multiple stages in the signal transduction cascade.

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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 29 publications

References 0 publications

The Role of Arachidonic Acid in Steroidogenesis and Steroidogenic Acute Regulatory (StAR) Gene and Protein Expression

The Role of Arachidonic Acid in Steroidogenesis and Steroidogenic Acute Regulatory (StAR) Gene and Protein Expression

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

24R,25-(OH)2D3 mediates its membrane receptor-dependent effects on protein kinase C and alkaline phosphatase via phospholipase A2 and cyclooxygenase-1 but not cyclooxygenase-2 in growth plate chondrocytes

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