VASOPRESSIN AND INSULIN-LIKE GROWTH-FACTORS SYNERGISTICALLY INDUCE MYOGENESIS IN SERUM-FREE MEDIUM

Terminal differentiation of myogenic cells has long been known to be p ositively regulated by insulin-like growth factors (IGFs), Arg(8)-vaso pressin (AVP) has been recently reported to potently induce myogenic d ifferentiation, In the present study, the effects and the mechanisms o f action of AVP and IGFs on myogenic cells have been investigated unde r conditions allowing growth and differentiation of myogenic cells in a simple serum-free medium, Under these conditions, L6 and L5 myogenic cells slowly proliferate and do not undergo differentiation (less tha n 1% fusion up to 7 days). AVP rapidly (2-3 days) and dose-dependently induces the formation of multinucleated myotubes. Creatine kinase act ivity and myosin accumulation are strongly up-regulated by AVP. Insuli n or IGF-I or IGF-II, at concentrations that Cause extensive different iation in serum-containing medium, induces a modest degree of differen tiation in serum-free medium, The simultaneous presence of AVP and of one of the IGFs in the synthetic medium induces maximal differentiatio n of L6, L5, and satellite cells, The expression of both myogenin and Myf-5 is dramatically stimulated by AVP, Our results indicate that AVP induces a significant level of myogenic differentiation in the absenc e of other factors. Furthermore, they suggest that to express their fu ll myogenic potential, IGFs require the presence of other factors norm ally present in serum and fully mimicked by AVP, These studies support the conclusion that terminal myogenic differentiation may depend on t he presence of differentiation factors rather than the absence of grow th factors.