GDF-8

Myostatin (GDF-8) is a secreted TGF-beta superfamily member that serves as the principal negative regulator of skeletal muscle mass. It signals through activin type IIB receptors (ActRIIB) and type I receptors (ALK4/ALK5), activating Smad2/3 transcription factors that suppress myogenic gene expression (MyoD, myogenin) and inhibit satellite cell activation, myoblast proliferation, and differentiation. Myostatin loss-of-function mutations produce dramatic muscle hypertrophy in multiple species. The propeptide remains associated with mature myostatin as an inhibitor until cleaved by BMP-1/tolloid proteases.