Follistatin was initially isolated from porcine follicular fluid. Follistatin is a single chain glycoprotein that inhibits the secretion of FSH from the pituitary. Follistatin is a TGF-β family member antagonist, which along with other antagonists (noggin, chordin, DAN/Cerberus), binds to the ligands and interfere with their binding to the receptors. Follistatin binds to Activin with high affinity (Kd ～45 pM), but it also binds other ligands with lower affinity, these additional ligands include: BMPs 2, 4, 6, 7, 11, and 15, and myostatin. It is known that follistatin knockout mice display defects in skeleton and muscle development size; therefore, they die shortly after birth. Follistatin is expressed in the ovary, kidney, and brain. In the ovary, follistatin mRNA expression is low in primordial follicles, but increases in the granulosa cells in secondary and tertiary follicles. Also, follistatin is produced by the liver and it seems to be the major source of follistatin in human serum. Changes in follistatin and activin expression have been associated with hepatic diseases such as inflammation, fibrosis, liver failure, and hepatocellular carcinoma.