1988 Fiscal Year Final Research Report Summary
Structures and function of the sugar chains of glycohormones.
| Project/Area Number |
62480449
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KOBATA Akira Professor, the University of Tokyo, 医科学研究所, 教授 (30030852)
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| Co-Investigator(Kenkyū-buntansha) |
AMANO Junko Technical Official of Ministry of Education, the University of Tokyo, 医科学研究所, 教務職員 (10159460)
ENDO Tamao Assistant, the University of Tokyo, 医科学研究所, 助手 (30168827)
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| Project Period (FY) |
1988
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| Keywords | Glycoprotein / Human chorionic gonadotropin / Follicle stimulating hormone / Sialic acid / Asparagine-linked sugar chain / Mucin-type sugar chain / Adenylyl cyclase / Ley-dig細胞 |
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| Research Abstract |
Four glycoprotein hormones so for reported in mammals are composed of two non-covalently linked subunits: and . Studies of amino acid sequences of the two subunits of the four glycohormones have revealed that their -subunits have an identical structure within an animal species. Because of this, it has been believed without proof that the specificity of each hormone to bind to its target cells resides in its -subunit. Removal of sugar chains from human chorionic gonadotropin (hCG) by enzymatic or by chemical means does not affect its in vitro binding to the receptor of target cells, but leads to a drastic drop in the biological activity of the hormone. Based on this interesting evidence, we tried to elucidate the functional role of the sugar chains of glycohormones more, concretely. The major evidences revealed by the two years of study are as follows.
1) Human FSH was found to contain different set of asparagine-linked sugar chains from hCG. Accordingly, the -subunits of glycohormones should no more be considered the same. 2) A portion of the monoantennary complex-type asparagine-linked sugar chains, which is detected in the -subunit of hCH, was chemically synthesized. This monoatennary pentasaccharide showed a weak inhibitory activity when added to hcG-MA10 cell system. 3) Isomeric hCG, in which all sialic acid residues occur as the Neu5Ac 2 6Gal group, showed exactly the same hormonal activity in vitro as natural hCG which contains the Neu5Ac 2 3Gal group only. 4) Studies of choriocarcinoma hCG and invasive mole hCG revealed that the more the sugar chains are altered, the less hormonal activity is expressed. These results indicated that both sialic acid residues and the remaining part of oligosaccharides play important roles in the expression of hormonal activity of hCG.
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