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Study on novel molecular mechanisms for thyroid dysfunction

Research Project

Project/Area Number 17590484
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionGunma University

Principal Investigator

MURAKAMI Masami  Gunma University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (30241871)

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)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
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)
KeywordsHypothyroidism / Thyroid Stimulating Hormone / Iodothyronine Deiodinase / Autoimmunity
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.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (15 results)

All 2007 2006 2005

All Journal Article (15 results)

  • [Journal Article] Thyroglobulin gene mutations producing defective intracellular transport of thyroglobulin are associated with increased thyroidal type 2 iodothyronine deiodinase activity.2007

    • Author(s)
      Kanou et al.
    • Journal Title

      J Clin Endocrinol Metab 92

      Pages: 1451-1457

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Rapid SNP diagnostics using asymmetric isothermal amplification and a new mismatch-suppression technology.2007

    • Author(s)
      Mitani et al.
    • Journal Title

      Nature Methods 4

      Pages: 257-262

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Thyroglobulin gene mutations producing defective intracellular transport of thyroglobulin are associated with increased thyroidal type 2 iodothyronine deiodinase activity.2007

    • Author(s)
      Kanou et al.
    • Journal Title

      J Clin Endocrinal Metab 92

      Pages: 1451-1457

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Thyroglobulin gene mutations producing defective intracellular transport of thyroglobulin are associated with increased thyroidal type 2 iodothyronine deiodinase activity/2007

    • Author(s)
      Kanou et al.
    • Journal Title

      J Clin Endocrinol Metab 92

      Pages: 1451-1457

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification and functional analysis of novel inactivating thyrotropin receptor mutations in patients with thyrotropin resistance.2006

    • Author(s)
      Tsunekawa et al.
    • Journal Title

      Thyroid 16

      Pages: 471-479

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Regulation of iodothyronine deiodinase and roles of thyroid hormones in human coronary artery smooth muscle cells.2006

    • Author(s)
      Kasahara T et al.
    • Journal Title

      Atherosclerosis 186

      Pages: 207-214

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Unique regulation of thyroid hormone metabolism during fasting in the house musk shrew (Suncus murinus, Insectivora : Soricidae).2006

    • Author(s)
      Takeuchi Y et al.
    • Journal Title

      Gen Comp Endocrinol 146

      Pages: 236-241

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 甲状腺癌2006

    • Author(s)
      村上 正巳
    • Journal Title

      検査と技術 34

      Pages: 812-818

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Expression of type 2 iodothyronine deiodinase in human osteoblast is stimulated by thyrotropin.2005

    • Author(s)
      Morimura T et al.
    • Journal Title

      Endocrinology 146

      Pages: 2077-2084

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Association of antipituitary antibody and type 2 iodothyronine deiodinase antibody in patients with autoimmune thyroid disease.2005

    • Author(s)
      Nakahara R et al.
    • Journal Title

      Endocrine J 52

      Pages: 691-699

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Association of antipituitary antibody and type 3 iodothyronine deiodinase antibody in patients with autoimmune thyroid disease.2005

    • Author(s)
      Nakahara R et al.
    • Journal Title

      Endocrine J 52

      Pages: 691-699

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression of type 2 iodothyronine denominate in human osteobiast is stimulated by thyrotropin.2005

    • Author(s)
      Morimura T et al.
    • Journal Title

      Endocrinology 146

      Pages: 2077-2084

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Association of human follitropin(FSH)receptor with splicing variant of human lutropin/choriogonadotropin receptor negatively controis the expression of human FSH receptor.2005

    • Author(s)
      Yamashita S et al.
    • Journal Title

      Mol Endocrinol 19

      Pages: 2099-2111

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Long-term outcome of interferon-alpha-induced autoimmune thyroid disorders in chronic hepatitis C.2005

    • Author(s)
      Doi F et al.
    • Journal Title

      Liver Int 25

      Pages: 242-246

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 甲状腺疾患の診断と治療における臨床検査2005

    • Author(s)
      村上 正巳
    • Journal Title

      日本臨床検査自動化学会会誌 30

      Pages: 193-198

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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