title: Topographical differences in human choriogonadotropin antagonist as revealed by monoclonal antibodies.
abstract: Human choriogonadotropin (hCG), a highly glycosylated hormone loses its biological activity following deglycosylation. The deglycosylated hormone (DG-hCG) binds to gonadal cell receptors without causing complete signal transduction. In order to analyze the molecular features of DG-hCG, we have prepared and studied five monoclonal antibodies (Mab). Two DG-hCG Mabs were highly specific while three others showed some but low cross-reactivity with hCG. Only those that recognized hCG albeit weakly, could inhibit binding of 125I-hCG to receptors or hCG action in MA-10 (mouse Leydig tumor cells). All five Mabs were highly reactive with the free alpha subunit. As these alpha subunit favoring antibodies easily recognized DG-hCG but not the intact hCG configuration, we suggest that loss of sugars in alpha and beta subunits of DG-hCG was responsible for these alterations. Thus, in the molecular topography of DG-hCG, the orientation of the alpha subunit would be different from that in the native hormone and this may be further perturbed following binding to the specific receptor, leading to inefficient coupling to the signal transducing machinery.
authors.affiliation: Reproduction Research Laboratory, Clinical Research Institute of Montreal, Québec, Canada.
authors.forename: L G
authors.initials: LG
authors.lastname: Jiang
authors.forename: M R
authors.initials: MR
authors.lastname: Sairam
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D006063:Chorionic Gonadotropin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006031:Glycosylation; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011974:Receptors, LH / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000911:Antibodies, Monoclonal; D006063:Chorionic Gonadotropin; D011974:Receptors, LH