Ligand-induced receptor dimerization may be critical for signal transduction by choriogonadotropin.

A mechanism of signal transduction by human choriogonadotropin (hCG) has been proposed. Competitive inhibition of the binding of hCG to its receptor by the serine protease inhibitors led to the identification of local structural homology of an extracellular region of the receptor with the reactive site loop of chymotrypsin inhibitor. Synthetic peptides from the extracellular domain of luteinizing hormone-choriogonadotropin (LH/CG) receptor, rationally designed on the basis of this homology, were found to affect hormone-receptor binding and bioactivity. A receptor peptide incorporating one complete structural unit of the leucine-rich repeats motif of the extracellular domain of the receptor significantly increased hCG-receptor binding in a dose-dependent manner. However, the testosterone production in a Leydig cell bioassay was inhibited in the presence of this peptide. The agonistic effect on the hCG-receptor binding and the antagonistic effect on the testosterone production of a receptor peptide suggests the possibility of more than one quasi-equivalent receptor-binding site on the hormone. Hormone-induced receptor oligomerization may therefore be involved in the mechanism of signal transduction by hCG.