Mechano growth factor (MGF) is an alternatively spliced variant of insulin-like growth factor-I (IGF-I). Previous reports have revealed that the MGF in skeletal muscles is induced by mechanical overload or muscle injury. In the present study, we examined the effect of growth hormone (GH) on MGF expression in C2C12 mouse muscle cell lines since GH is the principal regulator of IGF-I. The MGF mRNA increased 1 h following GH stimulation whereas IGF-IEa mRNA, which encodes a systemic type of IGF-I, increased 4 h following GH stimulation. The diverse expression of MGF and IGF-IEa was also observed in the case of muscle injury by using bupivacaine in the same cell line. Furthermore, GH induced the increase of MyoD as well as M-cadherin expression, the peak of which was parallel to that of MGF. These results indicate that GH directly and preferentially increased MGF prior to the IGF-IEa expression in C2C12 cells, which may lead to the activation of muscle satellite cells.