Study on novel molecular mechanisms for thyroid dysfunction
| Project/Area Number |
17590484
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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 |
Laboratory medicine
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| Research Institution | Gunma University |
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Principal Investigator |
MURAKAMI Masami Gunma University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (30241871)
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| Co-Investigator(Kenkyū-buntansha) |
KUWABARA Atsushi Gunma University, School of Medicine, Research Associate, 医学部, 助手 (90323344)
OGIWARA Takayuki Gunma University, School of Medicine, Research Associate, 医学部, 助手 (80361377)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Hypothyroidism / Thyroid Stimulating Hormone / Iodothyronine Deiodinase / Autoimmunity |
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| Research Abstract |
Thyroxine (T4) needs to be converted to 3,5,3'-triiodothyronine (T3) by iodothyronine deiodinase to exert its biological activity. There are type 1(D1) and type 2 (D2) of iodothyronine deiodinase that activates t4. We have demonstrated that D2 exists in human osteoblasts, and its activity is stimulated by thyroid stimulating hormone (TSH) via TSH receptor. We have also demonstrated that T3, which is produced from T4 by D2, inhibits proliferation and migration activities of human cardiac arterial smooth muscle cells.
Serum T3 is increased compared to T4 in patients with thyroglobulin mutation. We have demonstrated that D2 activity is increased in the thyroid tissue of patients with thyroglobulin mutation, which may result in increased T3 secretion from thyroid gland.
Recently, single nucleotide polymorphism (SNP) inD2 has been reported to be associated with insulin resistance. We have successfully developed a rapid and reliable method to detect D2 SNP accurately.
We have identified novel TSH receptor mutations in patients with TSH resistance. The patients were compound heterozygote of V473I/R450H, R519C/R450H. We have studied TSH binding, cAMP response, IP response and cell surface expression of mutant TSH receptors expressed is COS-7 cells. These novel TSH receptor mutations demonstrated the close relationship between clinical signs including serum TSH levels and functions of mutant TSH receptors. R450H mutation is commonly observed TSH receptor mutation in patients with TSH resistance in Japan.
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Report
(3 results)
Research Products
(15 results)
