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Gene Expression of Iodothyronine Deiodinase in Human

Research Project

Project/Area Number 08671191
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionKansai Medical University

Principal Investigator

NISHIKAWA Mitsushige  Kansai Medical University, 2nd Department of Internal Medicine, Associate Professor, 医学部, 助教授 (40156055)

Co-Investigator(Kenkyū-buntansha) TOYODA Nagaoki  Kansai Medical University, 2nd Department of Internal Medicine, Assistant, 医学部, 助手 (90278630)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsDeiodinase / Graves' disease / Mononuclear cells / mRNA / Gene expression
Research Abstract

Iodothyronine deiodinase catalyzes the conversion from thyroxine (T4) to triiodothyronine (T3), an active thyroid hormone. Two distinct deiodinases, Type 1 (D1) and Type 2 (D2) are known in both rodents and humans. D1 plays an important role to produce T3 and supply T3 to peripheral organs, whereas D2 is essential to the local supply of T3 in some specific organs including brain and pituitary.Complementary DNA for both D1 and D2 are identified and they were found to have a rare amino acid, selenocystein, at the catalytic unit. D1 in rats is increased by T3 and cyclic AMP,however, the regulatory mechanisms of D1 and D2 in humans are not clear partly because of the difficulty of the experimental materials. The purpose of the present study is to elucidate the mechanisms of the gene expression of D1 and D2 in human.
We utilized peripheral blood mononuclear cells (PBMC) for quantification of human D1. PBMC were isolated from normal volunteers and patients with hyperthyroidism using Ficoll-Hypaque gradient centrifugation from about 10 ml peripheral blood. D1 mRNA in PBMC was isolated and quantified by reverse transcriptase protein chain reaction using deleted mutated D1 cDNA.D1 mRNA of hyperthyroid Graves's disease was significantly higher than that of normal controls. There was a significant, positive correlation between D1 mRNA and serum T3 concentration. However, there was not a significant correlation between D1 mRNA in PBMC and serum activity of anti-thyrotropin receptor antibody. When T3 was added to cultured PBMC,D1 mRNA in PBMC was significantly increased. These findings indicate that the present method is valid for quantifying human D1 in PBMC and that D1 mRNA in PBMC is up-regulated by T3 in humans. We have shown an activity for D2 and D2 mRNA in human thyroid tissue. The regulatory mechanism of D1 and D2 in human thyroid tissue is being investigated.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Nishikawa M, et al.: "Evaluation of type I iodothyronine deiodinase mRNA levels in peripheral blood mononuclear cells." Thyroid. 6S1. S57 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nishikawa M, et al.: "Occult papillary thyroid carcinoma in Hashimoto's thyroiditis presenting as a metastatic bone tumor." Thyroid. 7S1. S65 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toyoda N, et al.: "Induction of type II deiodinase by cAMP and cGMP at pretranslational level in cultured rat glial cells." Thyroid. 7S1. S37 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tabata S, et al.: "Effect of streptozotocin(STZ)-induced diabetes mellitus(DM) on type I deiodinase in inherited D1-deficient mice(C3H)" Thyroid. 6S1. S89 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshikawa N, et al.: "Simultaneous xenotransplantation of human Graves' thyroid tissue and autologous bone marrow cells in severe combined immunodeficient mice:successful reconstitution of human Graves' hyperthyroidism." European Journal of Endocrinology. 136. 213-222 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toyoda n, et al.: "The structure of the coding and 5'-flanking region of the type I iodothyronine deiodinase(diol) gene is normal in a patient with suspected congenital diol deficiency." Journal of Clinical Endocrinology and Metabolism. 81. 2121-2124 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nishikawa M,Toyoda N,Tabata S,Ogawa Y,Inada M: "Evaluation of type 1 iodothyronine deiodinase m RNA levels in peripheral blood mononuclear cells." Thyroid. 6S1. S-57 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshikawa N,Nishikawa M,Mori S,Tokoro T,Yamamoto Y,Ikehara S,Kumazawa H,Yamashita T,Inada M: "Simultaneous xenotransplantation of human Graves' thyroid tissue and autologous bone marrow cells in severe combined immunodeficient mice : successful reconstitution of human Graves' hyperthyroidism." European Journal of Endocrinology. 136. 213-222 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tabata S,Toyoda N,Ogawa Y,Nishikawa M: "Effect of streptozotocin (STZ) -induced diabetes mellitus (DM) on type 1 deiodinase in inherited D1-deficient mice (C3H)." Thyroid. 6S1. S-89 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toyoda N,Kleinhaus N,Larsen PL: "The structure of the coding and 5'-flanking region of the type 1 iodothyronine deiodinase (diol) gene is normal in a patient with suspected congenital diol deficiency." Journal of Clinical Endocrinology and Metabolism. 81. 2121-2124 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Toyoda N,Gondou A,Tabata S,Yonemoto T,Ogawa Y,Sakaguchi, N,Nishikawa M,Inada M: "Induction of type II deiodinase by cAMP and cGMP at pretranslational level in cultured rat glial cells." Thyroid. 7S1. S-37 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nishikawa M, et al: "Evaluation of type 1 iodothyronie deiodinase m RNA levels in peripheral blood mononuclear cells." Thyroid. 6S1. S-57 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nishikawa M, et al: "Occult papillary thyroid carcinoma in Hashimoto′s thyroidtis presenting as a metastatic bone tumor." Thyroid. 7S1. S-65 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Toyoda N, et al.: "Induction of type II deiodinase by cAMP and cGMP at pretranslational level in cultured rat glial cells." Thyroid. 7S1. S-37 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tabata S, et al.: "Effect of streptozocin(STZ)-induced diabetes mellitus (DM)on type 1 deiodinase in inherited D1-deficient mice(C3H)" Thyroid. 6S1. S-89 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 西川光重: "ヒト末梢血単核球における1型ヨードサイロニン脱ヨード酵素(D1)mRNAの発現" 日本内分泌学会雑誌. 72・2. 309 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 豊田長興: "ヒト1型ヨードサイロニン脱ヨード酵素遺伝子構造の解析とその臨床応用" 日本内分泌学会雑誌. 72・2. 309 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 田端作好: "1型ヨードサイロニン脱ヨード酵素(D1)低発現マウス(C3H)のD1活性におよぼす糖尿病の影響" 日本内分泌学会雑誌. 72・2. 310 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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