Role of intramitochondrial arachidonic acid and acyl-CoA synthetase 4 in angiotensin II-regulated aldosterone synthesis in NCI-H295R adrenocortical cell line

Endocrinology. 2012 Jul;153(7):3284-94. doi: 10.1210/en.2011-2108. Epub 2012 May 1.


Although the role of arachidonic acid (AA) in angiotensin II (ANG II)- and potassium-stimulated steroid production in zona glomerulosa cells is well documented, the mechanism responsible for AA release is not fully described. In this study we evaluated the mechanism involved in the release of intramitochondrial AA and its role in the regulation of aldosterone synthesis by ANG II in glomerulosa cells. We show that ANG II and potassium induce the expression of acyl-coenzyme A (CoA) thioesterase 2 and acyl-CoA synthetase 4, two enzymes involved in intramitochondrial AA generation/export system well characterized in other steroidogenic systems. We demonstrate that mitochondrial ATP is required for AA generation/export system, steroid production, and steroidogenic acute regulatory protein induction. We also demonstrate the role of protein tyrosine phosphatases regulating acyl-CoA synthetase 4 and steroidogenic acute regulatory protein induction, and hence ANG II-stimulated aldosterone synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / metabolism*
  • Angiotensin II / metabolism*
  • Animals
  • Arachidonic Acid / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cattle
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Leydig Cells / metabolism
  • Male
  • Mitochondria / metabolism*
  • Phospholipases A2 / metabolism
  • Zona Glomerulosa / metabolism


  • ASCL4 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Angiotensin II
  • Arachidonic Acid
  • Aldosterone
  • Phospholipases A2