The role of carbohydrate in human choriogonadotropin (hCG) action. Effects of N-linked carbohydrate chains from hCG and other glycoproteins on hormonal activity.
Deglycosylation of gonadotropins and thyrotropin results in a major loss of hormonal bioactivity, while not impairing receptor-binding activity. However, a direct role of the glycan moieties in hormonal signal transduction has not been demonstrated. The addition of carbohydrate chains together with the deglycosylated hormone does not restore the hormonal activity. In contrast, glycopeptides were found to inhibit human choriogonadotropin (hCG)-stimulated adenylyl cyclase activity and hCG binding to its receptor. An inhibition of hCG-stimulated adenylyl cyclase activity but not hCG binding to receptor by glycopeptides specifically from hCG, has previously been reported as a lectin-like membrane component has been implicated in hCG action. In the present study we have shown that glycopeptides and oligosaccharides prepared from hCG, transferrin, fetuin, alpha 1-acid glycoprotein and ovalbumin inhibit the binding of hCG to its receptor. The inhibition was also observed with a highly purified preparation of the receptor, thus suggesting a lack of involvement of other lectin-like membrane components as previously proposed. We suggest that a lectin-like interaction with the hormone, if any, involves the receptor itself. Adenylyl cyclase activity stimulated by hCG, isoproterenol or forskolin was inhibited by oligosaccharides, indicating a non-specific interaction. Our results suggest that Asn-linked oligosaccharide chains from various glycoproteins perturb hCG-receptor interactions through a putative carbohydrate binding site on the receptor.
Molecular, Cellular and Nutritional Endocrinology Branch, NIDDK, NIH, Bethesda, MD 20892.
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Thotakura
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Weintraub
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D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology*; D006801:Humans; D009844:Oligosaccharides / Q000494:pharmacology*; D010047:Ovalbumin / Q000494:pharmacology; D010053:Ovary / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology; D051381:Rats; D011974:Receptors, LH / Q000378:metabolism*; D015398:Signal Transduction; D014168:Transferrin / Q000494:pharmacology; D000509:alpha-Fetoproteins / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D006063:Chorionic Gonadotropin; D006020:Glycopeptides; D009844:Oligosaccharides; D011134:Polysaccharides; D011974:Receptors, LH; D014168:Transferrin; D000509:alpha-Fetoproteins; D010047:Ovalbumin; D000262:Adenylyl Cyclases