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 ske letal 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 (Ba rton-Davis et al. 1998). We have proposed that this functional hypertrophy is primarily owing to the activation of satellite cells which leads to incr eased muscle regeneration. In order to test if satellite cells are essentia l in mediating the hypertrophic effects of IGF-I, we used gamma radiation t o destroy the proliferative capacity of satellite cells. The right hindlimb s of adult C57BL/ 6 male mice were subjected to one of the following treatm ents: (1) 2500 rad gamma radiation only, (2) viral-mediated gene transfer o f IGF-I only, (3) 2500 rad gamma radiation plus viral-mediated gene transfe r of IGF-I, or (4) no intervention as a control. Approximately 4 months aft er treatment, the extensor digitorum longus muscles (EDL) from both hindlim bs were removed for mechanical and morphological measurements. Treatment wi th gamma radiation significantly prevented normal growth of the muscle. Whe n combined with IGF-I treatment, approximately half of the IGF-I effect was prevented by gamma radiation treatment. This suggests that the remaining h alf of IGF-I induced hypertrophy is owing to paracrine/autocrine effects on the adult myofibres. Thus, these data are consistent with a mechanism by w hich IGF-I induced muscle hypertrophy via a combination of satellite cell a ctivation and increasing protein synthesis in differentiated myofibres.