Growth Factor Research
Research Only
Follistatin
Also known as: FS-344, FST, follistatin, activin binding protein
Naturally occurring glycoprotein that binds myostatin. Studied in myostatin-pathway research.
Research overview
Follistatin is a naturally occurring glycoprotein (a protein with sugar chains attached), first isolated from ovarian follicular fluid as a protein that inhibits release of follicle-stimulating hormone (FSH) from the pituitary. The human gene makes two precursor forms, of 344 and 317 amino acids; "Follistatin 344" (FS344) names the longer one, and the mature protein is about 315 amino acids, so it is a protein rather than a short peptide. Interest for muscle research comes from animals: mice engineered to make extra follistatin in muscle had large increases in muscle mass (Lee and McPherron, PNAS 2001), and macaques given the FS344 gene in a virus vector had larger, stronger thigh muscles.
In people, the only published studies are two small gene therapy trials from one US group, six patients each with Becker muscular dystrophy or inclusion body myositis, with no placebo group; the second trial's claims were publicly disputed. These delivered the FS344 gene, not the protein. There are no published controlled human trials of follistatin protein. An anti-doping analysis of 17 products sold online as FS344 found follistatin in only nine (Reichel et al., Drug Test Anal 2019). Long-term safety and effects outside muscle are not known. Supplied for laboratory research use only.
Mechanism of action
Follistatin is a binding protein rather than a receptor agonist. It binds activins and myostatin, members of the TGF-beta family of growth-signalling proteins, in the fluid around cells, and in lab binding tests it stopped myostatin from binding its receptor, activin receptor type IIB (Lee and McPherron, 2001). Blocking this signal in mice, by making extra follistatin in muscle, gave muscle increases similar to those in mice lacking myostatin. It was first identified as a protein that inhibits FSH release from the pituitary.
