ARGININE-VASOPRESSIN INDUCES DIFFERENTIATION OF SKELETAL MYOGENIC CELLS AND UP-REGULATION OF MYOGENIN AND MYF-5

The neurohypophyseal nonapeptide arginine(8)-vasopressin (AVP) induces phosphoinositide turnover and calcium and pH changes in skeletal myogenic cells in culture. In order to investigate the effect of AVP on skeletal myogenesis, we examined the effect of this hormone on proliferating mononucleated L6 myoblast cultures. Addition of AVP to the medium resulted in the formation of much larger myotubes than those formed in its absence and in a significant increase (2.2-fold) of the percentage of fusion within 3-4 days of treatment. The effect of AVP was dose dependent, in the 10 nM to 1 mu M range, and was observed also in primary cultures of mouse satellite cells. The rate of growth of L6 cells was not affected by AVP treatment. The induction of morphological differentiation by AVP correlated with an increased expression of muscle-specific gene products, such as myosin, and an increased number of acetylcholine receptor sites. The accumulation of mRNA transcripts of the acetylcholine receptor subunits was also enhanced by AVP. The mechanism involved in the myogenic action of AVP was investigated. Using AVP-related peptides and antagonists, we found that a specific chemical structure is required and that V1 receptors probably mediate the effect on myogenesis. Expression of muscle-specific transcription factor genes Myf-5 and myogenin and their products are strongly upregulated by AVP. Our findings support the hypothesis that AVP may represent a novel physiological modulator of skeletal muscle differentiation through its action on muscle regulatory genes.