Insulin-like growth factor-I induces androgen receptor activation in differentiating C2C12 skeletal muscle cells.
The modulating effect of IGF-I on the regulation of AR gene expression and activation in skeletal muscle cells remains poorly understood. In this study, the effects of IGF-I treatment on AR induction and activation in the absence of AR ligands were examined. Differentiating C2C12 cells were treated with different concentrations (0-250 ng/ml) of IGF-I or for various periods of time (0-60 min) of 250 ng/ml IGF-I. Treatment of C2C12 cells with IGF-I resulted in a dose- and time-dependent increase in total AR and phosphorylated AR (Ser 213). IGF-I treatment also led to significantly increased AR mRNA expression when compared with the control. The levels of skeletal alpha-actin and myogenin mRNA, known target genes of AR, were also significantly upregulated after 5 or 10 min of treatment with IGF-I. Confocal images revealed that IGF-I stimulated nuclear localization of AR in the absence of ligands. In addition, an electrophoretic mobility shift assay indicated that IGF-I stimulated the AR DNA binding activity in a time-dependent manner. The present results suggest that IGF-I stimulates the expression and activation of AR by ligand-independent mechanism in differentiating C2C12 mouse skeletal muscle cells.
Kim
Hye Jin
HJ
Department of Exercise Science, College of Health Sciences, Ewha Womans University, Seoul, Korea.
Lee
Won Jun
WJ
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*
D012333:RNA, Messenger; D011944:Receptors, Androgen; D007334:Insulin-Like Growth Factor I