How β₂-adrenergic agonists induce skeletal muscle hypertrophy?

抄録

Some β₂-adrenergic agonists (β₂-agonists) can strongly induce muscular hypertrophy, and are prohibited to use as doping drugs for athletes. The pharmacological mechanism for such induced hypertrophy is not clear. These agonists affect many organs via the cAMP-PKA system. Muscular hypertrophy is most likely induced by way of protein synthesis via the IGF-1/PI3K/PKB system and negative myostatin pathway. There are some reports indicating that β₂-agonists might stimulate protein synthesis via the IGF-1/PI3K/PKB system. Furthermore, it inhibits proteolysis via the ATP-dependent ubiquitin-proteasome system (UPS), autophagy-lysosome system and calcium-calpain system. In this review, some discrepancies are introduced between a basic hypertrophic mechanism and inhibited atrophic mechanism using β₂-agonists. Surfaces of muscle fiber might have some various receptors, and the β₂-adrenoceptor might be activated directly by PI3K via Gα_s to trigger skeletal muscle hypertrophy. β₂-agonists might be stimulated to synthesize follistatin of the myostatin inhibitor, as well as to produce satellite cells. Furthermore, increased myostatin may work to determine the size of each muscle fiber, and an increased number of quiescent satellite cells serve as myonuclei donors for hypertrophied muscle fibers. Recently, it was reported that follistatin synthesis was regulated by microRNAs. The effect of microRNA on β₂-agonists is not clear. In the cAMP/PKA/CREB pathway, β₂-agonists might inhibit various proteolytic systems, resulting in an increase of structural proteins. But β₂-agonists have more pharmacological functions like lipolytic action and stimulation of the central nervous system; thus, more research and analysis is needed.