Preferential masking by the receptor of immunoreactive sites on the alpha subunit of human choriogonadotropin.
125I-Labeled human choriogonadotropin (125I-hCG) bound to rat ovarian receptor was solubilized in Triton X-100. By using increasing concentrations of nine different antisera specific for the individual subunits of human choriogonadotropin (hCG), free 125I-hCG or 125I-hCG-receptor complex was precipitated by double-antibody technique. The ability of any antiserum to bind to the hormone-specific beta subunit was not affected by hCG binding to receptor, suggesting that this subunit is not directly involved with the receptor in the final state of the hormone-receptor complex. In contrast, every antiserum specific for the alpha subunit was dramatically inhibited in binding to the solubilized 125I-hCG-receptor complex. These results suggest that the alpha subunit directly interacts with the receptor, thereby masking immunoreactive sites normally available on the free hormone. Because a number of reports describe binding activity of high concentrations of immunopurified beta subunits of hCG, we propose a two-step model for the binding of hCG to receptor and postulate separate and distinct roles for the subunits. We propose that the binding of hCG to the receptor involves a specific low-affinity initial interaction of the beta subunit with the receptor that activates a second site for the high-affinity binding of alpha subunit and stabilization of the hormone-receptor complex.
D000818:Animals; D000936:Antigen-Antibody Complex; D001667:Binding, Competitive; D006063:Chorionic Gonadotropin / Q000276:immunology / Q000378:metabolism*; D003429:Cross Reactions; D004054:Diethylstilbestrol / Q000494:pharmacology; D005260:Female; D015292:Glycoprotein Hormones, alpha Subunit; D007106:Immune Sera; D046911:Macromolecular Substances; D010053:Ovary / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011555:Pseudopregnancy / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011974:Receptors, LH
D000936:Antigen-Antibody Complex; D006063:Chorionic Gonadotropin; D015292:Glycoprotein Hormones, alpha Subunit; D007106:Immune Sera; D046911:Macromolecular Substances; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011974:Receptors, LH; D004054:Diethylstilbestrol