Induction of steroidogenesis in immature rat Leydig cells by interleukin-1α is dependent on extracellular signal-regulated kinases
Autor: | Youngah Jo, Olof Söder, Mikael Holst, Irina Svechnikova, N. Renlund, Konstantin Svechnikov, Douglas M. Stocco |
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Rok vydání: | 2006 |
Předmět: |
Male
MAPK/ERK pathway Time Factors Biology Mitochondrion Rats Sprague-Dawley Endocrinology Nitriles Butadienes medicine Animals Phosphorylation Inner mitochondrial membrane Protein Kinase Inhibitors Molecular Biology Cells Cultured Protein Kinase C Protein kinase C Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Leydig cell Kinase Leydig Cells Biological Transport Cell Differentiation Cyclic AMP-Dependent Protein Kinases Rats Cell biology Enzyme Activation Cholesterol medicine.anatomical_structure Mitochondrial Membranes Steroids Signal transduction Interleukin-1 |
Zdroj: | Journal of Molecular Endocrinology. 36:327-336 |
ISSN: | 1479-6813 0952-5041 |
Popis: | 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. |
Databáze: | OpenAIRE |
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