Human chorionic gonadotropin (hCG) is a member of the glycoprotein hormone family which includes FSH. hCG TSH. These hormone family is characterized by a heterodimeric structure composed a common $alpha$-subunit noncovalently linked to a hormone specific $eta$-subunit. To determine u and $eta$ -subunits can be synthesized as a single polypeptide chain (tethered-hCG) and also display biological activity, the tethered-hCC and -FSH molecule by fusing the carboxyl terminus of the hCG $eta$-subunit to the amino terminus of the $alpha$-subunit was constructed. To determine the importance of $alpha$ COOH -terminal amino acid, we also deleted the $alpha$ COOH-terminal amino acids. The expressing vectors were transfected into CHO-K 1 cells. The tethered-wthCG and -wtFSH was efficiently secreted. The $alpha$ Δ83hCG and $alpha$ Δ 83FSH mutants had no secretion. These results are the first conclusive evidence that COOH-terminal amino acids are very important for secretion in human glycoprotein hormone $alpha$-subunit. These results demonstrated that the $alpha$ Δ83hCG and $alpha$ Δ 83FSH mutants could be play a pivotal role in the secretion of tethered-molecule.