Altered glycosylation of human chorionic gonadotropin decreases its hormonal activity as determined by cyclic-adenosine 3',5'-monophosphate production in MA-10 cells.
Human chorionic gonadotropin (hCG) purified from pooled urine of normal pregnant women contains four asparagine-linked sugar chains and four mucin-type sugar chains. The structures of asparagine-linked sugar chains of this hormone are constant and site-specific. hCGs obtained from the urine of patients with invasive mole or choriocarcinoma have quite different sets of oligosaccharides although the primary structures of the polypeptides and the numbers of the sugar chains are the same as those of normal hCG. In order to examine the biological activities of these hCGs with altered glycosylation, we measured the amount of cAMP produced in a murine Leydig tumour cell line, MA-10, after incubation with the hCG samples. The extent of sialylation of oligosaccharides in the three hCG samples used in this study were 88% in normal hCG, 82% in invasive mole hCG and 63% in choriocarcinoma hCG. The hormonal activity of invasive mole hCG was slightly lower while that of choriocarcinoma hCG was significantly (P less than 0.01) lower than that of normal hCG. Complete desialylation induced remarkable loss of full activities in all the samples. However, the hormonal activities of the three samples were different even after desialylation. The full activities of the desialylated samples of invasive mole hCG and choriocarcinoma hCG were 78 and 65% of that of desialylated normal hCG. These results indicated that the structures of the neutral oligosaccharide portion are also important for the expression of full hormonal activity.
Amano
J
J
Department of Biochemistry, University of Tokyo, Japan.
Nishimura
R
R
Sato
S
S
Kobata
A
A
D000818:Animals; D002240:Carbohydrate Sequence; D002460:Cell Line; D002822:Choriocarcinoma / Q000473:pathology / Q000652:urine*; D006063:Chorionic Gonadotropin / Q000737:chemistry / Q000494:pharmacology* / Q000652:urine; D000242:Cyclic AMP / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014644:Genetic Variation; D006031:Glycosylation; D006801:Humans; D006828:Hydatidiform Mole / Q000473:pathology / Q000652:urine*; D007984:Leydig Cell Tumor; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009690:Nucleic Acid Conformation; D009844:Oligosaccharides / Q000737:chemistry* / Q000302:isolation & purification; D011247:Pregnancy; D012016:Reference Values; D014594:Uterine Neoplasms / Q000473:pathology / Q000652:urine*
D006063:Chorionic Gonadotropin; D009844:Oligosaccharides; D000242:Cyclic AMP