To address this limitation, toward the systematization of a ‘multi-dimensional mechanism’ model, here we review the molecular mechanisms underlying exercise-induced physiological cardiac hypertrophy, with particular focus on how physical activity regulates hormones and growth factors including insulin-like growth factor-1, vascular endothelial growth factor, neuregulin-1, and norepinephrine. The gene discussed is IGF1; the disease is cardiac hypertrophy.