Group X secretory phospholipase A2 regulates the expression of steroidogenic acute regulatory protein (StAR) in mouse adrenal glands

Preetha Shridas, William M. Bailey, Boris B. Boyanovsky, Rob C. Oslund, Michael H. Gelb, Nancy R. Webb

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

We developed C57BL/6 mice with targeted deletion of group X secretory phospholipase A2 (GX KO). These mice have ∼80% higher plasma corticosterone concentrations compared with wild-type (WT) mice under both basal and adrenocorticotropic hormone (ACTH)-induced stress conditions. This increased corticosterone level was not associated with increased circulating ACTH or a defect in the hypothalamic-pituitary axis as evidenced by a normal response to dexamethasone challenge. Primary cultures of adrenal cells from GX KO mice exhibited significantly increased corticosteroid secretion compared with WTcells. Conversely, overexpression of GX secretory phospholipase A2 (sPLA2), but not a catalytically inactive mutant form of GX sPLA 2, significantly reduced steroid production 30-40% in Y1 mouse adrenal cell line. This effect was reversed by the sPLA2 inhibitor, indoxam. Silencing of endogenous M-type receptor expression did not restore steroid production in GX sPLA2-overexpressing Y1 cells, ruling out a role for this sPLA2 receptor in this regulatory process. Expression of steroidogenic acute regulatory protein (StAR), the rate-limiting protein in corticosteroid production, was ∼2-fold higher in adrenal glands of GX KO mice compared with WT mice, whereas StAR expression was suppressed in Y1 cells overexpressing GX sPLA2. Results from StAR-promoter luciferase reporter gene assays indicated that GX sPLA2 antagonizes StAR promoter activity and liver X receptor-mediated StAR promoter activation. In summary, GX sPLA2 is expressed in mouse adrenal glands and functions to negatively regulate corticosteroid synthesis, most likely by negatively regulating StAR expression.

Original languageEnglish
Pages (from-to)20031-20039
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number26
DOIs
StatePublished - Jun 25 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Group X secretory phospholipase A2 regulates the expression of steroidogenic acute regulatory protein (StAR) in mouse adrenal glands'. Together they form a unique fingerprint.

Cite this