Antibodies against human chorionic gonadotropin convert the deglycosylated hormone from an antagonist to an agonist.
Chemical deglycosylation of human chorionic gonadotropin (hCG) produced an antagonist (DG-hCG) that specifically bound to hCG receptors but was no longer able to stimulate adenylate cyclase in the murine Leydig tumor cell line, MLTC-1. DG-hCG was restored to an agonist by incubating cells or membranes having the bound analogue with antibodies against hCG (anti-hCG). In the presence of anti-hCG, cyclic AMP accumulation and adenylate cyclase activity were stimulated over DG-hCG alone. There was no accumulation of cyclic AMP when the cells were exposed to anti-hCG alone or DG-hCG and normal serum or anti-hCG first then DG-hCG. Several different batches of anti-hCG were effective but their activity did not correlate with their affinity for DG-hCG or hCG. The effect of anti-hCG on DG-hCG activity was dose- and time-dependent. Maximal stimulation of cyclic AMP was achieved with antisera dilutions of 1:200 or less. When DG-hCG-treated cells were exposed to anti-hCG at 37 degrees C, there was a 10-min lag. The lag was eliminated when the cells were exposed to the antibodies at 4 degrees C for 3 h and then warmed to 37 degrees C. Adenylate cyclase was also activated when Fab fragments prepared by papain digestion of anti-hCG were used, whereas Fc fragments were not effective. Thus, the divalency of the anti-hCG is not the critical factor in the mechanism of antibody action. Our results suggest that anti-hCG converts DG-hCG from an antagonist to an agonist possibly by altering the conformation of the modified hormone.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000906:Antibodies; D000936:Antigen-Antibody Complex; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D007700:Kinetics; D007984:Leydig Cell Tumor / Q000378:metabolism; D008297:Male; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism; D011974:Receptors, LH
D000906:Antibodies; D000936:Antigen-Antibody Complex; D006063:Chorionic Gonadotropin; D011956:Receptors, Cell Surface; D011974:Receptors, LH; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine