Vasoactive intestinal peptide (VIP)-mediated expression and function of steroidogenic acute regulatory protein (StAR) in granulosa cells

Mariusz P. Kowalewski, Matthew T. Dyson, Alois Boos, Douglas M. Stocco*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

VIP is a peptide hormone capable of activating the cAMP/PKA pathway and modifying gonadal steroidogenic capacity. Less is known about the molecular mechanisms of VIP-mediated steroidogenesis and its role in regulating the steroidogenic acute regulatory protein (STAR). We examined the impact of VIP on STAR expression and function in immortalized (KK1) and primary mouse granulosa cells, where VIP strongly upregulated STAR expression and steroidogenesis. Inhibitors of the PKA and PKC pathways suggested that both are activated by VIP. VIP did not efficiently phosphorylate STAR (P-STAR); however, VIP together with cAMP-analogs that activate Type II PKA increased P-STAR and further increased steroidogenesis. Our results suggest that VIP-induced STAR expression and function in granulosa cells result from the preferential activation of Type I PKA. Furthermore, the PKA and PKC pathways appear to converge at regulating VIP-mediated Star transcription and translation.

Original languageEnglish (US)
Pages (from-to)93-103
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume328
Issue number1-2
DOIs
StatePublished - Oct 2010

Keywords

  • Granulosa cells
  • STAR
  • Steroidogenesis
  • VIP

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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