Human exercise-mediated skeletal muscle hypertrophy is an intrinsic process.

Muscle cells (fibres) are post-mitotic and thus undergo changes in phenotype by modifying their existing structure. Hypertrophy is a hallmark change that occurs in response to increased loading and can be achieved in humans through repeated bouts of resistance exercise (i.e., training). In resistance exercise, contractions are initiated by neural drive leading to immediate perturbations such as calcium influx, cross-bridge cycling and tension/stress on the cytoskeleton, sarcolemma and extracellular matrix, as well as more delayed cellular events such as the production/release of potential local growth factors (e.g., IGF-1). Resistance exercise can also elevate the systemic concentration of certain hormones (growth hormone, testosterone, IGF-1) that are hypothesized to drive hypertrophy. However, while these hormones are clearly anabolic during childhood and puberty, or when given at supraphysiological exogenous doses, the transient post-exercise elevations in hormone concentration are of little consequence to the either the acute protein synthetic response or to a hypertrophic phenotype after resistance training. Thus, the acute post-exercise increases in systemic hormones are in no way a proxy marker for anabolism since they do not underpin the capacity of the muscle to hypertrophy in any measurable way. In contrast, the acute activation of intrinsically located signalling proteins such as p70(S6K) and the acute elevation of muscle protein synthesis are more reflective of the potential to increase in muscle mass with resistance training. Ultimately, local mechanisms are activated by the stress imposed by muscle loading and prime the muscle for protein accretion. Membrane-derived molecules and tension-sensing pathways are two intrinsic mechanisms implicated in upregulating the synthesis and incorporation of muscle proteins into the myofibre in response to mechanical stress derived from loaded contractions. Copyright (c) 2010 Elsevier Ltd. All rights reserved.