人TSH受容体モノクロナール抗体を用いたTSH受容体の形態学的証明

Material type: 文書・図像類

Author: 水上, 勇治ほか

Publisher: 金沢大学保健学系

Publication date: 1995-03

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Note (General)：: 甲状腺濾胞細胞におけるTSH受容体は、甲状腺濾胞細胞の機能と増殖をコントロールする最も重要な膜受容体である。最近慢性甲状腺炎、グレブス病患者において患者血中にTSH受容体に対する自己抗体が存在することが知られ、これにはblocking typeとstimulating typeがあり、共に患者の甲状...

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Material Type: 文書・図像類
Title: 人TSH受容体モノクロナール抗体を用いたTSH受容体の形態学的証明
Author/Editor: 水上, 勇治
Mizukami, Yuji
Author Heading: 水上, 勇治
Mizukami, Yuji
Publication, Distribution, etc.: 金沢大学保健学系
Publication Date: 1995-03
Publication Date (W3CDTF): 1995-03
Alternative Title: Immunohistochemical demonstration of thyrotropin (TSH) -receptor in normal and diseased human thyroid tissues using monoclonal antibody against recombinant human TSH-receptor protein
Periodical title: 平成6(1994)年度科学研究費補助金一般研究(C) 研究成果報告書 = 1994 Fiscal Year Final Research Report
No. or year of volume/issue: 1993-1994
Volume: 1993-1994
Pages: 8p.-
Text Language Code: jpn
Subject Heading: TSH受容体
免疫組織化学
モノクロナール抗体
Up-regulation
Up-reguration
TSH-receptor
Monoolonal antibody
Immunohistochemistry
Human thyroids
Target Audience: 一般
Note (General): 甲状腺濾胞細胞におけるTSH受容体は、甲状腺濾胞細胞の機能と増殖をコントロールする最も重要な膜受容体である。最近慢性甲状腺炎、グレブス病患者において患者血中にTSH受容体に対する自己抗体が存在することが知られ、これにはblocking typeとstimulating typeがあり、共に患者の甲状腺機能に深く関与している。また甲状腺癌においてもTSH受容体が存在し、癌の増殖、進展に深く関与していることが明らかとされている。しかしこのTSH受容体の分子構造や性状については十分に解明されておらず、また形態学的にも、TSH受容体の濾胞細胞での存在部位、種々の甲状腺疾患におけるTSH受容体の量的及び局在の変化については、現在まで全く明らかとされていなかった。本研究では、フランス国立内分泌研究所Milgrom教授より供与された、この人TSH受容体β-subunit蛋白に対するモノクロナール抗体を用い、甲状腺組織におけるTSH受容体の局在、分布に関する免疫組織化学的検討を行ってきた。その結果、TSH受容体は甲状腺濾胞細胞の基底側細胞膜に存在し、その蛋白量は甲状腺腺腫、癌で正常甲状腺に比し増加し、さらにGraves病甲状腺では極めて増加していることを明らかとした。このことは腺腫、癌でTSH受容体が保たれていること、又グレブス病甲状腺ではTSH受容体がup-regulateされ、これがGraves病における甲状腺機能亢進の病因の一つとなっている可能性を示唆するものであった(Mizukami Y.et al.J Clin Endocrinol Metab.79:616,1994)。さらに私達はTSH受容体の発現を蛋白レベルのみならず、さらにmessenger RNAレベルでも検討し、免疫組織化学的に得られた結果をさらに検証すべきと考え、現在western blotting法およびin situ hybridization法を用いて検討中である。
The TSH-receptor plays a key role in the control of thyroid function and proliferation. To demonstrate this receptor in normal and diseased human thyroid tissues, we performed an immunohistochemical analysis using a monoclonal antibody (T3-356) against recombinant human TSH receptor protein, which recognizes an epitope within the fragment in position 604-764 of human TSH-receptor (C-terminal region) .In normal human thyroid tissues, a positive staining was observed exclusively along the basal cell surface of the flattened follicular cells. In the tissues from adenomatous nodules, adenomas and papillary carcinomas, a positive staining was also found along basal cell surface of the follicular cells, and in addition, a considerable cytoplasmic staining was also observed. Apical and lateral cell surface of the follicular cells showed no staining. The staining intensity was more intense in the papillary carcinomas and follicular adenomas, and it was less intense in the oxyphilic cell adenom as and adenomatous nodules compared with the normal thyroid tissues. The foci of squamous cell metaplasia of papillary carcinomas, anaplastic carcinoma and medullary carcinoma did not show a positive staining. These findings indicate that TSH-receptor is preserved essentially in the basal cell surface of the thyroid follicular cells in neoplastic conditionsThree cases of Graves' disease had been preoperatively treated with anti-thyroid drugs, but were still hyperthyroid at surgery. The positive staining was also observed along the basal cell surface of the follicular cells from Graves' thyroids. The staining intensity was significantly increased in the Graves' thyroids compared with the normal thyroids. The most intense staining was noted in the foci of papillary projection of the columnar follicular cells of the Graves' thyroids. This immunohistochemical finding suggested that the number of TSH-receptors was increased in Graves' thyroids and that a down-regulatory mechanism of TSH-receptor may not be present in Graves' thyroids despite of the continuous stimulation of the thyroid follicular cells by the presence of stimulatory-type autoantibodies against TSH-receptor. Such findings may explain how stimulatory-type autoantibodies are able to act as a stimulator and maintain increased thyroid hormone production in Graves' disease.Further investigation using western blotting and in situ hybridization for quantitative analysis of TSH-receptor protein is performed.
研究課題/領域番号:05670169, 研究期間(年度):1993-1994
出典：「人TSH受容体モノクロナール抗体を用いたTSH受容体の形態学的証明」研究成果報告書　課題番号05670169 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)　　　本文データは著者版報告書より作成
DOI: 10.24517/00049263
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/search/?qm=60110540
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05670169/
https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-05670169/056701691994kenkyu_seika_hokoku_gaiyo/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA