FOLLISTATIN ACTIVIN COMPLEXES IN HUMAN SERUM AND FOLLICULAR-FLUID DIFFER IMMUNOLOGICALLY AND BIOCHEMICALLY

Follistatin (FS) is the principle high affinity activin-binding protei n in tissues such as the pituitary and ovary as well as in serum. In a ddition, 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 recombi nant human follistatin 288 (rhFS288) under a variety of incubation con ditions, further supporting the identification of the serum and hFF ac tivin-binding proteins as FS. Using enhanced resolution gel filtration , immunoprecipitation with monoclonal antibodies to rhFS288, and sulfa ted carbohydrate binding, activin-FS complexes in hFF and serum differ ed. 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 huma n serum elutes at an apparent M(r) of 60-70 kDa, is not precipitated b y anti-rhFS288 monoclonal antibodies, and is weakly bound by sulfate C ellufine 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 f or serum and hFF activin-binding proteins have implications for potent ial tissue-specific forms of FS that may well have distinct biological functions.