Identification of naturally occurring follistatin complexes in human biological fluids

Follistatin (FS) binds activin and inhibin proteins. Many organs are sensit ive to activin and inhibin; thus the formation of FS-activin/inhibin comple xes is important to our understanding of ligand activity Other investigator s studying FS have detected large molecular weight immunoreactive FS bands (greater than the expected molecular weight of FS alone) that have not been well characterized. The goal of this study was to identify naturally occur ring FS monomers and FS-activin/inhibin complexes in several organ systems. The pituitary, ovary, kidney, and urine were chosen for this investigation . Molecular masses were assigned to in vitro assemblies of complexes contai ning recombinant inhibin or activin with FS for comparison with naturally o ccurring FS forms. The recombinant complex of FS-activin was primarily 97-k Da size, while FS-inhibin complexes were detected in a range of molecular s izes from 66 kDa to 97 kDa, 133 kDa, and > 220 kDa. FS-containing complexes of 66-kDa, 97-kDa, and 133-kDa were identified in the tissues examined and in pregnant urine. Our study points to the assembly of a series of FS-acti vin/inhibin complexes in a variety of organ systems that may impact upon th e available amount of free versus bound (or "complexed") ligand, which must be considered when investigating the biology of activin- or inhibin-respon sive cells. In addition, urine may be an important biological fluid that ca n be used to measure significant changes in circulating FS complexes.