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

Objective: To test whether extension of the C-Cerminus of human chorionic g onadotropin (hCG) or-subunit (h alpha) alters the bioactivity of the recomb ined alpha beta heterodimer. Design: The stop codon of hot was mutated to produce a 24 amino acid extens ion. Methods: The extended h alpha (alpha(+24)) was co-expressed with hCG beta i n COS-7 cells and the receptor binding and in vivo bioactivity of the secre ted hormone was compared with its wild-type counterpart. Results: This extension did not impair the binding of hCG to rat LH/CC rece ptors and provoked a sixfold reduction in its stimulatory activity of testo sterone secretion in rat Leydig cells. Conclusions: The extension of alpha by itself does not lead to inhibition o f the alpha beta heterodimer to LH receptors but the structure of the exten sion appears to play an important role. It is thus possible that one-chain hCG chimeras with the beta N-terminus fused to the alpha C-terminus might b e active.