Endocrinology, Vol 137, 240-247, Copyright © 1996 by Endocrine Society

ARTICLES

Follistatin-activin complexes in human serum and follicular fluid differ immunologically and biochemically

AL Schneyer, HA Hall, G Lambert-Messerlian, QF Wang, P Sluss and WF Crowley Jr
Reproductive Endocrine Unit, Massachusetts General Hospital, Boston 02214, USA.

Follistatin (FS) is the principle high affinity activin-binding protein in tissues such as the pituitary and ovary as well as in serum. In addition, the activin-binding peaks identified after gel filtration of serum or human follicular fluid (hFF) exhibited high affinity and low reversibility binding kinetics, with higher concentrations in hFF than serum. This extremely low reversibility was also observed for recombinant human follistatin 288 (rhFS288) under a variety of incubation conditions, further supporting the identification of the serum and hFF activin-binding proteins as FS. Using enhanced resolution gel filtration, immunoprecipitation with monoclonal antibodies to rhFS288, and sulfated carbohydrate binding, activin-FS complexes in hFF and serum differed. The activin-FS complex in hFF elutes at approximately 200-300 kDa, is immunoprecipitated by anti-hFS288 monoclonal antibodies, and binds to sulfate Cellufine matrix, all characteristics similar to those of recombinant human FS288. In contrast, the activin binding peak in human serum elutes at an apparent Mr of 60-70 kDa, is no precipitated by anti-rhFS288 monoclonal antibodies, and is weakly bound by sulfate Cellufine matrix, characteristics shared by rhFS315 conditioned medium. As the forms of FS that bind sulfate-containing matrices also bind to cell surface proteoglycans, the molecular differences reported here for serum and hFF activin-binding proteins have implications for potential tissue- specific forms of FS that may well have distinct biological functions.

This article has been cited by other articles:

				Y. Xia and A. L Schneyer The biology of activin: recent advances in structure, regulation and function J. Endocrinol., July 1, 2009; 202(1): 1 - 12. [Abstract] [Full Text] [PDF]

				A. Veiga-Lopez, W. Ye, D.J. Phillips, C. Herkimer, P.G. Knight, and V. Padmanabhan Developmental Programming: Deficits in Reproductive Hormone Dynamics and Ovulatory Outcomes in Prenatal, Testosterone-Treated Sheep Biol Reprod, April 1, 2008; 78(4): 636 - 647. [Abstract] [Full Text] [PDF]

				B. Refaat, S. Amer, B. Ola, N. Chapman, and W. Ledger The Expression of Activin- A- and - B-Subunits, Follistatin, and Activin Type II Receptors in Fallopian Tubes Bearing an Ectopic Pregnancy J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 293 - 299. [Abstract] [Full Text] [PDF]

				A. L. Schneyer, Q. Wang, Y. Sidis, and P. M. Sluss Differential Distribution of Follistatin Isoforms: Application of a New FS315-Specific Immunoassay J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5067 - 5075. [Abstract] [Full Text] [PDF]

				H. T. Keutmann, A. L. Schneyer, and Y. Sidis The Role of Follistatin Domains in Follistatin Biological Action Mol. Endocrinol., January 1, 2004; 18(1): 228 - 240. [Abstract] [Full Text] [PDF]

				L. M. Bilezikjian, A. M. O. Leal, A. L. Blount, A. Z. Corrigan, A. V. Turnbull, and W. W. Vale Rat Anterior Pituitary Folliculostellate Cells Are Targets of Interleukin-1{beta} and a Major Source of Intrapituitary Follistatin Endocrinology, February 1, 2003; 144(2): 732 - 740. [Abstract] [Full Text] [PDF]

				C. Welt, Y. Sidis, H. Keutmann, and A. Schneyer Activins, Inhibins, and Follistatins: From Endocrinology to Signaling. A Paradigm for the New Millennium Experimental Biology and Medicine, October 1, 2002; 227(9): 724 - 752. [Abstract] [Full Text] [PDF]

				V. Padmanabhan, D. Battaglia, M. B. Brown, F. J. Karsch, J. S. Lee, W. Pan, D. J. Phillips, and J. Van Cleeff Neuroendocrine Control of Follicle-Stimulating Hormone (FSH) Secretion: II. Is Follistatin-Induced Suppression of FSH Secretion Mediated via Changes in Activin Availability and Does It Involve Changes in Gonadotropin-Releasing Hormone Secretion? Biol Reprod, May 1, 2002; 66(5): 1395 - 1402. [Abstract] [Full Text]

				R. L. Jones, L. A. Salamonsen, Y. C. Zhao, J.-F. Ethier, A. E. Drummond, and J. K. Findlay Expression of activin receptors, follistatin and betaglycan by human endometrial stromal cells; consistent with a role for activins during decidualization Mol. Hum. Reprod., April 1, 2002; 8(4): 363 - 374. [Abstract] [Full Text] [PDF]

				T. Fujiwara, Y. Sidis, C. Welt, G. Lambert-Messerlian, J. Fox, A. Taylor, and A. Schneyer Dynamics of Inhibin Subunit and Follistatin mRNA during Development of Normal and Polycystic Ovary Syndrome Follicles J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4206 - 4215. [Abstract] [Full Text] [PDF]

				R. J. Norman, C. R. Milner, N. P. Groome, and D. M. Robertson Circulating follistatin concentrations are higher and activin concentrations are lower in polycystic ovarian syndrome Hum. Reprod., April 1, 2001; 16(4): 668 - 672. [Abstract] [Full Text] [PDF]

				D. J. Phillips, K. L. Jones, D. J. McGaw, N. P. Groome, J. J. Smolich, H. Pärsson, and D. M. de Kretser Release of Activin and Follistatin during Cardiovascular Procedures Is Largely due to Heparin Administration J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2411 - 2415. [Abstract] [Full Text]

				J. R. McFarlane, L. M. Foulds, A. E. O’Connor, D. J. Phillips, G. Jenkin, M. T. W. Hearn, and D. M. de Kretser Uterine Milk Protein, a Novel Activin-Binding Protein, Is Present in Ovine Allantoic Fluid Endocrinology, October 1, 1999; 140(10): 4745 - 4752. [Abstract] [Full Text]

				A. Delbaere, Y. Sidis, and A. L. Schneyer Differential Response to Exogenous and Endogenous Activin in a Human Ovarian Teratocarcinoma-Derived Cell Line (PA-1): Regulation by Cell Surface Follistatin Endocrinology, June 1, 1999; 140(6): 2463 - 2470. [Abstract] [Full Text]

				D. S. McConnell, Q. Wang, P. M. Sluss, N. Bolf, R. H. Khoury, A. L. Schneyer, A. R. Midgley Jr., N. E. Reame, W. F. Crowley Jr., and V. Padmanabhan A Two-Site Chemiluminescent Assay for Activin-Free Follistatin Reveals That Most Follistatin Circulating in Men and Normal Cycling Women Is in an Activin-Bound State J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 851 - 858. [Abstract] [Full Text]

				N. Di Simone, H. A. Hall, C. Welt, and A. L. Schneyer Activin Regulates {beta}A-Subunit and Activin Receptor Messenger Ribonucleic Acid and Cellular Proliferation in Activin-Responsive Testicular Tumor Cells Endocrinology, March 1, 1998; 139(3): 1147 - 1155. [Abstract] [Full Text] [PDF]