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Biology of Reproduction 60, 8-13 (1999)
©Copyright 1999 Society for the Study of Reproduction, Inc.

Identification of Naturally Occurring Follistatin Complexes in Human Biological Fluids1

Eileen Y. Wanga,b, Lawrence B. Draperb, Elbert Leeb, Amanda Polakc, Patrick Slussd, Jeffrey Weissc, and Teresa K. Woodruff2,b,c

a Department of Obstetrics and Gynecology, Northwestern University Medical School, Chicago, Illinois 60611 b Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208 c Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 60611 d Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts 02114

Follistatin (FS) binds activin and inhibin proteins. Many organs are sensitive to activin and inhibin; thus the formation of FS-activin/inhibin complexes is important to our understanding of ligand activity. Other investigators 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 occurring 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 containing recombinant inhibin or activin with FS for comparison with naturally occurring FS forms. The recombinant complex of FS-activin was primarily 97-kDa size, while FS-inhibin complexes were detected in a range of molecular sizes 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-activin/inhibin complexes in a variety of organ systems that may impact upon the available amount of free versus bound (or "complexed") ligand, which must be considered when investigating the biology of activin- or inhibin-responsive cells. In addition, urine may be an important biological fluid that can be used to measure significant changes in circulating FS complexes.

1 This work was supported by a Kroch Twin Grant (to E.W. and T.K.W.), an NIH core grant (P30-HD-28048 to T.K.W.), and by the National Center for Infertility Research (Grant U54-HD-29164 to T.K.W., J.W., P.S.).

2 Correspondence: Teresa K. Woodruff, Northwestern University, Department of Neurobiology and Physiology, O.T. Hogan 4–150, 2153 Sheridan Road, Evanston, IL 60208. FAX: 847 491 2224; tkw{at}nwu.edu




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