2000 Fiscal Year Final Research Report Summary
MECHANISM OF ONSET AND AGGRAVATION OF THYROTOXICOSIS IN PATIENTS WITH GRAVES' DISEASE
| Project/Area Number |
10671047
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | KANSAI MEDICAL UNIVERSITY |
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Principal Investigator |
NISHIKAWA Mitsushige INSTITUTOIN, DEPARTMENT, TITLE OF POSITION ; KANSAI MEDICAL UNIVERSITY, FACULTY OF MEDICINE, PROFESSOR, 医学部, 教授 (40156055)
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| Co-Investigator(Kenkyū-buntansha) |
TOYODA Nagaoki INSTITUTOIN, DEPARTMENT, TITLE OF POSITION ; KANSAI MEDICAL UNIVERSITY, FACULTY OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (90278630)
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| Project Period (FY) |
1998 – 2000
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| Keywords | deiodinase / Graves' disease / mRNA / PKA / PKC / thyroid / thyrotoxicosis / gene |
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| Research Abstract |
Type 1 and 2 iodothyronine deiodinases(D1 and D2)catalyze T4 activation. In human thyroid, unlike rodents, both D1 and D2 are expressed. To evaluate the regulatory mechanism of D1 and D2 expression in Graves' disease, we have measured the D1 mRNA in peripheral blood mononuclear cells(PBMC). We also have investigated the effects of TSH, (Bu)2cAMP, and TPA on the D2 mRNA levels and activity in cultured human thyroid cells.
D1 mRNA levels in PBMC were measured by using competitive reverse transcriptase-polymerase chain reaction with the deleted complimentary RNA of D1 as the standard for quantification. They increased significantly in Graves' disease than in normal controls. There was a significant positive correlation between D1 mRNA and serum T3 concentration. D1 mRNA levels increased by adding T3 dose-dependently in cultured PBMC.D2 mRNA levels in the cultured human thyroid cells, which were obtained from patients with Graves' disease at the time of thyroidectomy, were increased by TSH and(Bu)2cAMP.The increase of D2 mRNA was faster and the increment was greater than that of D1 mRNA levels. The increment of the Vmax value for D2 by(Bu)2cAMP stimulation was similar to that of D2 mRNA levels, suggesting that(Bu)2cAMP enhances D2 activity mainly at the pretranslational level. On the other hand, TPA suppressed the D2 mRNA levels in the absence and presence of(Bu)2cAMP.
These data suggest that (1) D1 gene expression in human PBMC is up-regulated by T3 and is responsible for the exacerbation of thyrotoxicosis in Graves' disease, and (2) D1 and D2 expression in human thyroid cells are regulated differently by the PKA and PKC pathways and both D1 and D2 could contribute to thyrotoxicosis in patients with Graves' disease.
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[Publications] Mitsushige Nishikawa, Nagaoki Toyoda, Toshinaga Yonemoto, Yoshifumi Ogawa, Sakuyoshi Tabata, Noriko Sakaguchi, Toshiko Tokoro, Atsushi Gondou, Masayoshi Yoshimura, Norio Yoshikawa, Mitsuo Inada.: "Quantitative measurement for type 1 deiodinase messenger ribonucleic acid in human peripheral mononuclear cells : mechanism of the preferential increase of T3 in hyperthyroid Graves' disease."Biochem Biophys Res Commun. 250. 642-646 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Atsushi Gondou, Nagaoki Toyoda, Mitsushige Nishikawa, Sakuyoshi Tabata, Toshinaga Yonemoto, Yoshifumi Ogawa, Toshiko Tokoro, Noriko Sakaguchi, Fangzheng Wang, Mitsuo Inada.: "Induction of type 2 deiodinase activity by cyclic guanosine 3', 5'-monophosphate in cultured rat glial cells."Thyroid. 8. 615-622 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sakuyoshi Tabata, Nagaoki Toyoda, Mitsushige Nishikawa, Toshinaga Yonemoto, Atsushi Gondou, Yoshifumi Ogawa, Noriko Sakaguchi, Toshiko Tokoro, Fangzheng Wang, Tamayo Kadobayashi, Yuko Imai, Mitsuo Inada.: "Effect of streptozotocin-induced diabetes mellitus on type 1 deiodinase (D1) in inherited D1-deficient mice."Endocrine J. 46. 497-504 (1999)
Description
「研究成果報告書概要(欧文)」より
