Follistatin has been considered primarily as the binding protein for activin; however, there is evidence that FS may serve other functions that do not relate to its ability to bind activin. FS-deficient mice demonstrate a variety of structural anomalies (shiny taut skin, thirteenth pair of ribs, whisker and tooth irregularities) and a failure to survive after birth, while activin-deficient mutant mice do not show such a widespread pattern of anomalies. This discordance of effects suggests that the impact of FS in development surpasses the range of effects with activin, implying that FS is more than just an activin bioneutralizer. This, in addition to recent data providing evidence that FS can inhibit the TGF-p effect on cytotrophoblast outgrowth, suggests that FS may also modulate other members of the TGF-p superfamily or may function independently of these ligands. The demonstration of the FS-inhibin complexes in the present study is intriguing; these complexes may in themselves serve a biological role as a ligand, as a possible method to sequester free FS from activin; but at present it is unclear what functional role, if any, exists for these complexes. ventolin 100 mcg
Our data illustrate the elaborate ability of FS to form complexes with activin and inhibin. Significantly, the free form of FS is not detected in biological tissues. While the bioneutralizing actions of FS on activin at the level of pituitary FSH secretion and erythroid cell differentiation are understood, FS regulation of inhibin, the presence of cell-bound FS, and potential conformational changes of FS-in-hibin/activin complex have not been correlated with functional roles in the kidney and other organs. The physiology of these alternative FS forms warrants investigation; in the meantime, the ability to detect changes in the levels of FS and inhibin in the urine in pregnancy should be further explored under the conditions of normal and abnormal pregnancy.