Human chorionic gonadotropin with C-elongated alpha-subunit retains full receptor binding and partial agonist activity.

Objective: To test whether extension of the C-terminus of human chorionic gonadotropin (hCG) a-subunit (ha) alters the bioactivity of the recombined ab heterodimer. Design: The stop codon of ha was mutated to produce a 24 amino acid extension. Methods: The extended ha (a+24) was co-expressed with hCGb in COS-7 cells and the receptor binding and in vivo bioactivity of the secreted hormone was compared with its wild-type counterpart. Results: This extension did not impair the binding of hCG to rat LH/CG receptors and provoked a sixfold reduction in its stimulatory activity of testosterone secretion in rat Leydig cells. Conclusions: The extension of a by itself does not lead to inhibition of the ab heterodimer to LH receptors but the structure of the extension appears to play an important role. It is thus possible that one-chain hCG chimeras with the b N-terminus fused to the a C-terminus might be active.