Induction of steroidogenesis in immature rat Leydig cells by interleukin-1α is dependent on extracellular signal-regulated kinases

N. Renlund, Y. Jo, I. Svechnikova, M. Holst, D. M. Stocco, O. Söder, Konstantin Svechnikov

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Interleukin-1α (IL-1α) plays an important role in the regulation of immune responses as well as in non-inflammatory events in different types of cells. Here we have investigated the involvement of the extracellular signal-regulated kinase (ERK) cascade in IL-1α-induced steroidogenesis by primary cultures of immature rat Leydig cells. Our findings indicate that protein kinase C functions as an upstream component of signal transduction from the IL-1 receptor type I (IL-1RI) to the ERK cascade. It was observed that IL-1α upregulated both steroidogenic acute regulatory (StAR) protein expression and its phosphorylation when compared with controls. Selective inhibition of these mitogen-activated protein kinases (MAPKs) by UO126 enhanced both the expression and phosphorylation of the StAR protein, but suppressed androgen production by the immature Leydig cells as well as dissipating the mitochondrial electrochemical potential (Ψm) in these cells. The evidence that water-soluble cholesterol but not 22R-hydroxycholesterol-stimulated steroidogenesis was inhibited by UO126 suggested that an intact Ψm across the inner mitochondrial membrane is required for cholesterol translocation and is positively regulated by the ERK cascade. We propose that activation of ERKs by IL-1α plays a dual role in the regulation of steroidogenesis in immature Leydig cells: these MAPKs downregulate StAR expression and phosphorylation, while at the same time they support an intact Ψm across the inner mitochondrial membrane, thereby promoting translocation of cholesterol into the mitochondria of the Leydig cell.

Original languageEnglish (US)
Pages (from-to)327-336
Number of pages10
JournalJournal of molecular endocrinology
Volume36
Issue number2
DOIs
StatePublished - Apr 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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