Human chorionic gonadotropin (hCG) contains five acidic N-linked
sugar chains, which are derived from three neutral
oligosaccharides by sialylation. Each of the two subunits (hCGalpha and hCGbeta) of hCG contain two glycosylated Asn residues.
Glycopeptides, each containing a single glycosylated Asn, were obtained by digestion of hCGalpha with
trypsin, and of hCGbeta with
chymotrypsin and
lysyl endopeptidase. Comparative study of the
sugar chains of the four
glycopeptides revealed the occurrence of site-directed glycosylation. Studies of the
sugar chains of hCGs, purified from urine of patients with various trophoblastic diseases, revealed that
choriocarcinoma hCGs contain sialylated or non-sialylated forms of eight neutral
oligosaccharides. In contrast, hCGs from
invasive mole patients contain sialyl derivatives 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 (
GnT-IV) is abnormally expressed in the malignant cells. This supposition was confirmed by molecular
biological study of
GnT-IV in placenta and
choriocarcinoma cell lines. The appearance of
tumor-specific
sugar chains in hCG has been used to develop a diagnostic method of searching for malignant trophoblastic diseases. In addition, a summary of the current knowledge concerning the functional role of N-linked
sugar chains in the expression of the hormonal activity of hCG has been presented.