Follistatin-activin complexes in human serum and follicular fluid differ immunologically and biochemically.
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.
Reproductive Endocrine Unit, Massachusetts General Hospital, Boston 02214, USA.
A L
AL
Schneyer
H A
HA
Hall
G
G
Lambert-Messerlian
Q F
QF
Wang
P
P
Sluss
W F
WF
Crowley
D028341:Activins; D002850:Chromatography, Gel; D016264:Dextran Sulfate; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism*; D038681:Follistatin; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007265:Inhibins / Q000097:blood / Q000378:metabolism*; D011233:Precipitin Tests; D011994:Recombinant Proteins
D038681:Follistatin; D006023:Glycoproteins; D011994:Recombinant Proteins; D028341:Activins; D007265:Inhibins; D016264:Dextran Sulfate