Follistatin (FS) is a monomeric glycoprotein that binds activins and inhibins. Since initial identification of FS as an inhibitor of FSH release, it has become clear that the role of FS action in the pituitary lies in its ability to bind and regulate activins. Activins and inhibins are disulfide-linked dimeric protein members of the transforming growth factor p (TGF-p) superfamily. Inhibins are he-terodimeric proteins composed of an a subunit and a p subunit, while activins are dimers of p subunits. Numerous studies of these proteins have centered on their roles in the reproductive axis, primarily in the pituitary and in the ovary—notablyinhibin’sinhibitoryeffectpponpituityyFSFI secretion and activin’s opposing effect. In addition to the ovary and pituitary, there is evidence that nongonadal tissues, such as endothelial, neural, muscular, and exocrine glandular tissues, produce FS and that FS mediates activin activity in these tissues.
Follistatin proteins have apparent molecular sizes of 32 and 35 kDa. These molecular size forms arise from alternatively spliced mRNAs between the fifth and sixth exons resulting in 288-amino acid (FS288) and 315 (FS315)-amino acid forms. The truncated FS288 protein binds cell surfaces through an exposed proteoglycan-binding domain, while the longer FS315 form does not seem to bind cell surface proteoglycans. The activin-binding site of FS is in the N-terminus, and all forms of FS bind activin with a similar affinity. FS proteins of 300 amino acids and 303 amino acids also exist and are the products of proteolytic processing. ventolin 100 mcg
Follistatin mRNA localization and accumulation have been examined in the ovary and pituitary throughout the reproductive cycle; however, the various FS proteins and protein complexes have not been well characterized in these or other tissues. The molecular weight of recombinant hormone complexes can be directly compared to that of detected FS forms from biologic specimens. In the present study we specifically investigated FS and FS complexes in the ovary and pituitary during the normal rat estrous cycle. In addition, FS protein was measured in the rat kidney, a tissue replete with FS, and in urine from pregnant women and rats. Identification of FS and FS complexes will allow further exploration of their function in these activin/inhibin-regulated tissues.