Preferential Masking by the Receptor of Immunoreactive Sites on the α 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), free125I-hCG or125I-hCG--receptor complex was precipitated by double-antibody technique. The ability of any antiserum to bind to the hormone-specific β 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 α subunit was dramatically inhibited in binding to the solubilized125I-hCG--receptor complex. These results suggest that the α 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 β 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 β subunit with the receptor that activates a second site for the high-affinity binding of α subunit and stabilization of the hormone--receptor complex.