1994 Fiscal Year Final Research Report Summary
Immunohistochemical demonstration of thyrotropin (TSH) -receptor in normal and diseased human thyroid tissues using monoclonal antibody against recombinant human TSH-receptor protein.
Project/Area Number |
05670169
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Human pathology
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Research Institution | Kanazawa University |
Principal Investigator |
MIZUKAMI Yuji Kanazawa Univ., Hosp., Pathology, Assistant Prof., 医学部・附属病院・病理部, 講師 (60110540)
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Co-Investigator(Kenkyū-buntansha) |
TAKIZAWA Takenori Kanazawa Univ., School of Medicine, Biochemistry, Assistant Prof., 医学部・生化学, 講師 (40192158)
MICHIGISHI Takatoshi Kanazawa Univ., Hosp., Nuclear Medicine, Assistant Prof., 医学部・附属病院・核医学, 講師 (60020012)
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Project Period (FY) |
1993 – 1994
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Keywords | TSH-receptor / Monoolonal antibody / Immunohistochemistry / Human thyroids / Up-reguration |
Research Abstract |
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
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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 conditions Three 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. Less
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Research Products
(4 results)
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[Publications] Mizukami, Y., Hashimato, T., Nonomura, A., Michigishi, T., Nakamura, S., Noguchi, M., Matsukawa, S.: "Immunohistochemical demonstration of thyrotropin (TSH) -receptor in normal and diseased human thyroid tissues using monoclonal antibody against recombinant human TSH-receptor protein." Crit.Rev.Oncol Hematol.18. 67-102 (1995)
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