Contribution of satellite cells to IGF-I induced hypertrophy of skeletal muscle.

Insulin-like growth factor I (IGF-I) is critical in promoting growth of skeletal muscle. When IGF-I is introduced into mouse hindlimb muscles by viral-mediated gene transfer, local overexpression of IGF-I produces significant increases in muscle mass and strength compared with untreated controls (Barton-Davis et al. 1998). We have proposed that this functional hypertrophy is primarily owing to the activation of satellite cells which leads to increased muscle regeneration. In order to test if satellite cells are essential in mediating the hypertrophic effects of IGF-I, we used gamma radiation to destroy the proliferative capacity of satellite cells. The right hindlimbs of adult C57BL/6 male mice were subjected to one of the following treatments: (1) 2,500 rad gamma radiation only, (2) viral-mediated gene transfer of IGF-I only, (3) 2,500 rad gamma radiation plus viral-mediated gene transfer of IGF-I, or (4) no intervention as a control. Approximately 4 months after treatment, the extensor digitorum longus muscles (EDL) from both hindlimbs were removed for mechanical and morphological measurements. Treatment with gamma radiation significantly prevented normal growth of the muscle. When combined with IGF-I treatment, approximately half of the IGF-I effect was prevented by gamma radiation treatment. This suggests that the remaining half of IGF-I induced hypertrophy is owing to paracrine/autocrine effects on the adult myofibres. Thus, these data are consistent with a mechanism by which IGF-I induced muscle hypertrophy via a combination of satellite cell activation and increasing protein synthesis in differentiated myofibres.