LIGAND-INDUCED RECEPTOR DIMERIZATION MAY BE CRITICAL FOR SIGNAL-TRANSDUCTION BY CHORIOGONADOTROPIN

A mechanism of signal transduction by human choriogonadotropin (hCG) h as been proposed. Competitive inhibition of the binding of hCG to its receptor by the serine protease inhibitors led to the identification o f local structural homology of an extracellular region of the receptor with the reactive site loop of chymotrypsin inhibitor. Synthetic pept ides from the extracellular domain of luteinizing hormone-choriogonado tropin (LH/CG) receptor, rationally designed on the basis of this homo logy, were found to affect hormone-receptor binding and bioactivity. A receptor peptide incorporating one complete structural unit of the le ucine-rich repeats motif of the extracellular domain of the receptor s ignificantly increased hCG-receptor binding in a dose-dependent manner . However, the testosterone production in a Leydig cell bioassay was i nhibited in the presence of this peptide. The agonistic effect on the hCG-receptor binding and the antagonistic effect on the testosterone p roduction of a receptor peptide suggests the possibility of more than one quasi-equivalent receptor-binding site on the hormone. Hormone-ind uced receptor oligomerization may therefore be involved in the mechani sm of signal transduction by hCG.