Structure, pathology and function of the N-linked sugar chains of human chorionic gonadotropin

Human chorionic gonadotropin (hCG) contains five acidic N-linked sugar chai ns, which are derived from three neutral oligosaccharides by sialylation. E ach of the two subunits (hCG alpha and hCG beta) of hCG contain two glycosy lated Asn residues. Glycopeptides, each containing a single glycosylated As n, were obtained by digestion of hCG alpha with trypsin, and of hCG beta wi th chymotrypsin and lysyl endopeptidase. Comparative study of the sugar cha ins of the four glycopeptides revealed the occurrence of site-directed glyc osylation. Studies of the sugar chains of hCGs, purified from urine of pati ents with various trophoblastic diseases, revealed that choriocarcinoma hCG s contain sialylated or non-sialylated forms of eight neutral oligosacchari des. In contrast, hCGs from invasive mole patients contain sialyl derivativ es of five neutral oligosaccharides. The structural characteristics of the five neutral oligosaccharides, detected in choriocarcinoma hCGs but not in normal placental hCGs, indicate that N-acetylglucosaminyltransferase IV (Gn T-IV) is abnormally expressed in the malignant cells. This supposition was confirmed by molecular biological study of GnT-IV in placenta and choriocar cinoma cell lines. The appearance of tumor-specific sugar chains in hCG has been used to develop a diagnostic method of searching for malignant tropho blastic diseases. In addition, a summary of the current knowledge concernin g the functional role of N-linked sugar chains in the expression of the hor monal activity of hCG has been presented. (C) 1999 Elsevier Science B.V. Al l rights reserved.