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2012 Fiscal Year Final Research Report

Molecular mechanism in the regulation of energy metabolism by nuclear hormone receptors

Research Project

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Project/Area Number 20591106
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionDepartment of Clinical Research, National Hospital Organization Kyoto Medical Center

Principal Investigator

TAGAMI Tetsuya  独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部(分子内分泌代謝), 研究室長 (60273439)

Co-Investigator(Kenkyū-buntansha) MORIYAMA Kenji  武庫川女子大学, 薬学部, 教授 (00301739)
NARUSE Mitsuhide  独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究部長 (40120018)
Co-Investigator(Renkei-kenkyūsha) YAMAMOTO Hiroyuki  武庫川女子大学, 薬学部, 助教 (10466295)
Project Period (FY) 2008 – 2012
Keywords甲状腺ホルモン受容体 / PPAR / 核内受容体 / ミトコンドリア脱共役蛋白 / 転写制御
Research Abstract

A novel thyroid hormone receptor β isoform (TR.4), recently we have cloned from human pituitary, may modulate hormone action as an endogenous antagonist in the tissue or cellular context. For example, aberrant expression of TR.4 may partly contribute to the inappropriate secretion of TSH in a TSHoma. Sites for co-repressors (CoR), co-activators (CoA), and RXR binding partially overlapped, but CoR and CoA bindings were well correlated with T3-independent and T3-dependent transcriptional regulations, respectively, while RXR binding was not among TR mutants, suggesting that transcriptional regulation by TR is mainly mediated by an exchange of CoRs and CoAs. Telmisartan, one of angiotensin II receptor blockers, specifically activates PPARγ. Telmisartan and thiazolidinediones (TZDs) had differential effects on the transcriptional control and interaction with cofactors among PPARγ mutants, suggesting that these mutants could be powerful tools for developing novel therapeutic agents that retain the metabolic efficacy of PPARγ activation with fewer adverse effects associated with TZDs. Moreover, we have studied the effects of FFA, fibrates or irbesartan on TR or PPAR mediated transcription, the search for PPAR activators in herb, and the crosstalk between nuclear hormone receptors and transcription factors that mediate GH/IGF-1 action or glucose, lipid and energy metabolism.

  • Research Products

    (26 results)

All 2013 2012 2011 2010 2009 2008

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (12 results) Book (4 results)

  • [Journal Article] Serum levels of IgG and IgG4 in Hashimoto thyroiditis.2013

    • Author(s)
      Kawashima ST, Tagami T, Naruse M,
    • Journal Title

      Endocrine.

      Volume: [Epub ahead of print]

    • URL

      http://link.springer.com/article/10.1007%2Fs12020-013-9988-9

    • Peer Reviewed
  • [Journal Article] Short-term effects of s-adrenergic antagonists and methimazole in new-onset thyrotoxicosis caused by Graves' disease.2012

    • Author(s)
      Tagami T, Naruse M.
    • Journal Title

      Intern Med

      Volume: 51 Pages: 2285-2290

    • URL

      https://www.jstage.jst.go.jp/article/internalmedicine/51/17/51_51.7302/_article

    • Peer Reviewed
  • [Journal Article] Forkhead box A1 (FOXA1) and A2 (FOXA2) oppositely regulate human type 1 iodothyronine deiodinase gene in liver.2012

    • Author(s)
      Kanamoto N, Tagami T
    • Journal Title

      Endocrinology

      Volume: 153 Pages: 492-500

    • DOI

      doi:10.1210/en.2011-1310

    • Peer Reviewed
  • [Journal Article] Multi-center study on the prevalence of hypothyroidism in patients with hypercholesterolemia.2011

    • Author(s)
      Tagami T, Naruse M.
    • Journal Title

      Endocr J

      Volume: 58 Pages: 449-457

    • URL

      https://www.jstage.jst.go.jp/article/endocrj/58/6/58_K11E-012/_article

    • Peer Reviewed
  • [Journal Article] Aberrant expression of thyroid hormone receptor beta isoform may cause inappropriate secretion of TSH in a TSH-secreting pituitary adenoma.2011

    • Author(s)
      Tagami T, Moriyama K, Naruse M.
    • Journal Title

      J Clin Endocrinol Metab

      Volume: 96 Pages: E948-952

    • DOI

      doi:10.1210/jc.2010-2496

    • Peer Reviewed
  • [Journal Article] Monoclonal autoantibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample.2010

    • Author(s)
      Evans M, Sanders J, Tagami T
    • Journal Title

      Clin Endocrinol (Oxf)

      Volume: 73(3) Pages: 404-12

    • DOI

      doi:10.1111/j.1365-2265.2010.03831.x

    • Peer Reviewed
  • [Journal Article] Identification of a novel human thyroid hormone receptor beta isoform as a transcriptional modulator.2010

    • Author(s)
      Tagami T, Yamamoto Y, Moriyama K, Naruse M.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 396 Pages: 983-988

    • DOI

      doi:10.1016/j.bbrc.2010.05.038

    • Peer Reviewed
  • [Journal Article] Lipid profiles in the untreated patients with Hashimoto thyroiditis and the effects of thyroxine treatment on subclinical hypothyroidism with Hashimoto thyroiditis.2010

    • Author(s)
      Tagami T, Naruse M.
    • Journal Title

      Endocr J

      Volume: 57 Pages: 253-258

    • URL

      https://www.jstage.jst.go.jp/article/endocrj/57/3/57_K09E-315/_article

    • Peer Reviewed
  • [Journal Article] The retinoid X receptor binding to the thyroid hormone receptor : relationship with cofactor binding and trascriptional activity.2009

    • Author(s)
      Tagami T, Yamamoto Y, Moriyama K, Naruse M.
    • Journal Title

      J Mol Endocrinol

      Volume: 42 Pages: 415-428

    • DOI

      doi:10.1677/JME-08-0153

    • Peer Reviewed
  • [Journal Article] A selective peroxisome proliferator-activated receptor γ modulator, telmisartan, binds to the receptor in a different fashion from thiazolidinediones.2009

    • Author(s)
      Tagami T, Yamamoto Y, Moriyama K, Naruse M.
    • Journal Title

      Endocrinology

      Volume: 150 Pages: 862-870

    • DOI

      doi:10.1210/en.2008-0502

    • Peer Reviewed
  • [Presentation] 甲状腺ホルモンによる骨代謝、糖・脂質代謝に関わる遺伝子の転写調節2012

    • Author(s)
      田上哲也, 森山賢治, 二若久美, 島津章, 成瀬光栄
    • Organizer
      第55回日本甲状腺学会
    • Place of Presentation
      福岡
    • Year and Date
      20121129-1201
  • [Presentation] 新規甲状腺ホルモン受容体アイソフォームβ4の細胞内機能に関する基礎的検討2012

    • Author(s)
      安宅麻美, 二若久美, 山本裕之, 島津章, 成瀬光栄, 田上哲也, 森山賢治
    • Organizer
      第55回日本甲状腺学会
    • Place of Presentation
      福岡
    • Year and Date
      20121129-1201
  • [Presentation] GH/IGF-1下流の転写因子群と脂質・エネルギー代謝に関わる核内受容体ファミリー間のクロストークの解析2012

    • Author(s)
      田上哲也, 二若久美, 森山賢治, 臼井健, 成瀬光栄, 島津章
    • Organizer
      第85回日本内分泌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      20120419-21
  • [Presentation] PPARsに対するアゴニスト探索と作用評価の試み2012

    • Author(s)
      森山賢治, 李娟娥, 二若久美, 山本裕之, 安宅麻美, 田上哲也
    • Organizer
      第85回日本内分泌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      20120419-21
  • [Presentation] 新規甲状腺ホルモン受容体アイソフォームβ4の細胞内局在に関する基礎的検討2011

    • Author(s)
      安宅麻美, 山本裕之, 二若久美, 田上哲也, 森山賢治
    • Organizer
      第54回日本甲状腺学会
    • Place of Presentation
      大阪
    • Year and Date
      20111121-23
  • [Presentation] 漢方薬構成生薬中のPPARsに対する有効成分の探索と効果評価の試み2011

    • Author(s)
      森山賢治, 李娟娥, 山本裕之, 桑村優衣子, 安宅麻美, 田上哲也
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌
    • Year and Date
      20110519-21
  • [Presentation] イルベサルタンによるPPARδ活性化2011

    • Author(s)
      田上哲也, 臼井健, 山本裕之, 森山賢治, 島津章, 成瀬光栄
    • Organizer
      第84回日本内分泌学会
    • Place of Presentation
      神戸
    • Year and Date
      20110421-23
  • [Presentation] TSH産生下垂体腺腫における新規甲状腺ホルモン受容体アイソフォームの発現2010

    • Author(s)
      田上哲也, 山本裕之, 森山賢治, 紅粉陸男, 臼井健, 島津章, 成瀬光栄
    • Organizer
      第53回日本甲状腺学会
    • Place of Presentation
      長崎
    • Year and Date
      20101111-13
  • [Presentation] 新規甲状腺ホルモン受容体アイソフォームβ4に関する基礎的検討2010

    • Author(s)
      森山賢治, 山本裕之, 安宅麻美, 臼井健, 成瀬光栄, 田上哲也
    • Organizer
      第53回日本甲状腺学会
    • Place of Presentation
      長崎
    • Year and Date
      20101111-13
  • [Presentation] フィブラートによるPPAR活性化作用の分子メカニズム2009

    • Author(s)
      田上哲也, 山本裕之, 森山賢治, 沢井邦子, 臼井健, 島津章, 成瀬光栄
    • Organizer
      第82回日本内分泌学会学術総会
    • Place of Presentation
      前橋
    • Year and Date
      20090423-25
  • [Presentation] 長鎖脂肪酸が甲状腺ホルモンの転写活性に及ぼす影響評価2009

    • Author(s)
      森山賢治, 山本裕之, 野井亜沙美, 濱口亜紀, 臼井健, 田上哲也
    • Organizer
      第82回日本内分泌学会学術総会
    • Place of Presentation
      前橋
    • Year and Date
      20090423-25
  • [Presentation] 甲状腺ホルモン受容体(TR)のレチノイドX受容体(RXR)結合転写共役因子結合と転写活性の関係2008

    • Author(s)
      田上哲也, 森山賢治, 山本裕之, 臼井 健, 沢井邦子, 成瀬光栄
    • Organizer
      第81回日本内分泌学会学術総会
    • Place of Presentation
      青森
    • Year and Date
      20080516-18
  • [Book] 甲状腺疾患の診かた,考えかた.2012

    • Author(s)
      田上哲也
    • Total Pages
      145
    • Publisher
      中外医学社
  • [Book] 内分泌代謝専門医ガイドブック改訂第3版2012

    • Author(s)
      成瀬光栄, 平田結喜緒, 島津章(編)田辺晶代, 寺内康夫, 高橋裕, 竹内靖博, 田上哲也(編協)
    • Total Pages
      411
    • Publisher
      診断と治療社
  • [Book] 内分泌画像検査・診断マニュアル2011

    • Author(s)
      成瀬光栄, 織内昇, 平田結喜緒, 西川光重(編)田辺晶代, 田上哲也, 柴田洋孝, 山田正三(編協)
    • Total Pages
      235
    • Publisher
      診断と治療社
  • [Book] 甲状腺疾患診療マニュアル2009

    • Author(s)
      田上哲也, 伊藤公一, 成瀬光栄, 西川光重(編)
    • Total Pages
      157
    • Publisher
      診断と治療社

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Published: 2014-08-29  

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