SATELLITE CELLS AND MUSCLE HYPERTROPHY: ROLE OF IGF-I

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DESCRIPTION (Adapted from the applicant's abstract): Skeletal muscle enlargement in response to increased mechanical loading appears to include the proliferation and differentiation of satellite cells via myogenic processes which are similar to, but distinct from, the type of growth seen during both early development and maturation. Findings to date suggest that insulin like growth factor-1 (IGF-1), acting in an autocrine/paracrine mode, serves as a primary mediator of these myogenic mechanisms which support the hypertrophy process in mature skeletal muscle fibers. Potential mechanisms by which IGF-1 modulates the process of myogenic cell proliferation, differentiation, and fusion have been delineated using in vitro approaches. The premise is presented that relatively little is known with regard to whether the processes identified in vitro also occur in skeletal muscle in vivo under conditions in which myofibers undergo compensatory hypertrophy due to chronic increases in loading. The proposed objective of this proposal is to test the hypothesis that IGF-1 mediates muscle hypertrophy by promoting myogenic processes in vivo. The proposed experiments will employ rodent models that target individual skeletal muscles. The treatments will include the delivery of growth factors and / or inhibitory agents either alone or in conjunction with resistance training of the target muscle. Analyses will include morphological, biochemical, molecular, microscopic and electron microscopic measures of cellular proliferation, differentiation and fusion as well as quantification of hypertrophy responses including measurements of muscle function. The proposed experiments will elucidate the role of the IGF-1 signaling system in the hypertrophy process.