Interaction between arachidonic acid and cAMP signaling pathways enhances steroidogenesis and StAR gene expression in MA-10 Leydig tumor cells

Xing Jia Wang*, Matthew T. Dyson, Carolina Mondillo, Zoraida Patrignani, Omar Pignataro, Douglas M. Stocco

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Previous studies have demonstrated that trophic hormone stimulation induced cyclic AMP (cAMP) formation and arachidonic acid (AA) release from phospholipids and that both these compounds were required for steroid biosynthesis and steroidogenic acute regulatory (StAR) gene expression in MA-10 mouse Leydig tumor cells. The present study further investigates the synergistic effects of the AA and cAMP interaction on steroidogenesis. To demonstrate cAMP-induced AA release, MA-10 cells were pre-loaded with 3H-AA and subsequently treated with dibutyryl cyclic AMP (dbcAMP). Stimulation with dbcAMP significantly induced AA release in MA-10 cells to a level 145.7% higher than that of controls. Lowering intracellular cAMP concentration by expressing a cAMP-phosphodiesterase significantly reduced human chorionic gonadotrophin (hCG)-induced AA release. The dbcAMP-induced AA release was inhibited significantly by the phospholipase A2 (PLA2) inhibitor dexamethasone (Dex) and also by the protein kinase A (PKA) inhibitor H89, suggesting the involvement of PKA phosphorylation and/or PLA2 activation in cAMP-induced AA release. The effect of the interaction between AA and cAMP on StAR gene expression and steroid production was also investigated. While 0.2 mM dbcAMP induced only very low levels of StAR protein, StAR mRNA, StAR promoter activity and steroid production, all of these parameters increased dramatically as AA concentration in the culture medium was increased from 0 to 200 μM. Importantly, AA was not able to induce a significant increase in steroidogenesis at any concentration when used in the absence of dbcAMP. However, when used in concert with submaximal concentrations of dbcAMP (0.05 mm to 0.5 mm), AA was capable of stimulating StAR gene expression and increasing steroid production significantly. The results from this study demonstrate that AA and cAMP act in a highly synergistic manner to increase the sensitivity of steroid production to trophic hormone stimulation and probably do so by increasing StAR gene expression.

Original languageEnglish (US)
Pages (from-to)55-63
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume188
Issue number1-2
DOIs
StatePublished - Feb 25 2002

Keywords

  • Arachidonic acid
  • StAR
  • Steroidogenesis
  • cAMP

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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