The Mechanisms of Anabolic Steroids, Selective Androgen Receptor Modulators and Myostatin Inhibitors
Abstract
In the clinical setting, anabolic agents serve to ameliorate muscle-and bone-wasting diseases.However, many of these anabolic agents are also used by bodybuilders to surpass natural limits of body composition as performanceenhancing drugs (PEDs).The first generation of PEDs comprises testosterone-derived anabolic-androgenic steroids (AAS) which have demonstrated significant myotropic effects.However, AAS lack optimal tissue-selectively and thus, are prone to numerous adverse health consequences.Hence, a newer generation of PEDs, selective androgen receptor modulators (SARMs), was developed with the goal of achieving superior tissue-selectivity (i.e., exerting anabolic effects only in muscle and bone tissue, while minimally affecting other body systems).In general, AAS and SARMs enhance muscle growth primarily through androgen receptor (AR) agonism in target tissues.Despite multiple attempts, no single AAS nor SARM to date is completely risk free.As such, a significant portion of research efforts has been dedicated to manipulating anabolic pathways beyond the AR.Another class of PEDs, myostatin inhibitors, have shown to cause drastic muscle anabolism across multiple species by inhibiting myostatin, the primary deterrent to continuous muscle growth.The myostatin inhibitor, YK-11, blocks myostatin by upregulating its antagonist, follistatin.This effect appears to be mediated through the AR, suggesting a novel and promising gene-selective approach to engineering AR ligands that…
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