Pharmacology of doping agents—mechanisms promoting muscle hypertrophy

Doping with performance enhancing substances in professional andamateur sports has increasingly gained awareness. Furthermore, not only thenumber but also the variety of substances detected in sports has increased.Intending muscle growth, anabolic androgenic steroids (AAS) have beencomplemented by selective androgen receptor modulators (SARMs), β2-adrenergicagonists, estrogen receptor (ER) β agonists and peptide-hormones like growthhormone (GH), insulin-like growth factor-1 (IGF-1) and insulin. However, withrespect to therapeutic use, drugs which increase anabolic actions in the bodyare highly desired for treatment of cachexia, sarcopenia, etc. The aim of the following review is to elaborate on the agents’similarities and differences in mechanisms inducing muscle hypertrophy whilegiving an overview of the relevant signalling cascades. In addition to that,potential agents for treatment of catabolic diseases are identified.Information, onwhich this paper is based on, hasbeen collected from various publications which have been published inhigh-quality scientific journals. The insight obtained has shown that signalling pathways mediatinggenomic actions of steroids have already been well-characterised, while thereis still need for further research on the mechanisms of non-genomicactions and downstream pathways as well as on those of SARMs and β2-adrenergicagonists’ action. A new and promising target is the estrogen receptor β. Theuse of ER-β agonists, which are proposed to activate anabolic mechanismsindependently from androgen receptor activation, may prevent the non-desiredandrogenic effects, which are associated with AAS administration. Thus, theymay be considered a promising alternative for treatment of diseases, whichcause loss of muscle mass and cachexia. In this context, phytoecdysteroids,such as ecdysterone etc, are considered as an interesting class of substances,where further investigations are highly desired. Furthermore, some peptidehormones also promote muscle hypertrophy. The signalling mechanisms of growthhormone, IGF-1 and insulin are summarised. Finally, the potential of myostatininhibition is discussed