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The insulin-like growth factor signalling pathway is an important regulator of skeletal muscle growth. We examined the mRNA expression of components of the insulin-like growth factor (IGF) signalling pathway as well as Fibroblast Growth Factor 2 (FGF2) during maturation of myotubes in primary cell cultures isolated from fast myotomal muscle of Atlantic salmon ( Salmo salar ). The transcriptional regulation of IGFs and IGFBP expression by amino acids and insulin-like growth factors was also investigated. Proliferation of cells was 15% d −1  at days 2 and 3 of the culture, increasing to 66% d −1  at day 6. Three clusters of elevated gene expression were observed during the maturation of the culture associated with mono-nucleic cells ( IGFBP5.1  and  5.2 ,  IGFBP-6 ,  IGFBP-rP1 ,  IGFBP-2.2  and  IGF-II ), the initial proliferation phase ( IGF-I ,  IGFBP-4 ,  FGF2  and  IGF-IRb ) and terminal differentiation and myotube production ( IGF2R ,  IGF-IRa ). In cells starved of amino acids and serum for 72 h,  IGF-I  mRNA decreased 10-fold which was reversed by amino acid replacement. Addition of IGF-I and amino acids to starved cells resulted in an 18-fold increase in  IGF-I  mRNA indicating synergistic effects and the activation of additional pathway(s) leading to IGF-I production via a positive feedback mechanism.  IGF-II ,  IGFBP-5.1  and  IGFBP-5.2  expression was unchanged in starved cells, but increased with amino acid replacement. Synergistic increases in expression of  IGFBP5.2  and  IGFBP-4 , but not  IGFBP5.1  were observed with addition of IGF-I, IGF-II or insulin and amino acids to the medium. IGF-I and IGF-II directly stimulated  IGFBP-6  expression, but not when amino acids were present. These findings indicate that amino acids alone are sufficient to stimulate myogenesis in myoblasts and that IGF-I production is controlled by both endocrine and paracrine pathways. A model depicting the transcriptional regulation of the IGF pathway in Atlantic salmon muscle following feeding is proposed.

Transcriptional Regulation of the IGF Signaling Pathway by Amino Acids and Insulin-Like Growth Factors during Myogenesis in Atlantic Salmon