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Study of functional evolution of steroid hormone receptor protein

Research Project

Project/Area Number 19K06734
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44040:Morphology and anatomical structure-related
Research InstitutionHokkaido University

Principal Investigator

Katsu Yoshinao  北海道大学, 理学研究院, 教授 (00332180)

Co-Investigator(Kenkyū-buntansha) 漆谷 博志  会津大学短期大学部, 食物栄養学科, 准教授 (30571301)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsステロイドホルモン受容体 / 軟骨魚類 / 分子進化 / 機能進化 / ホルモン応答性 / ステロイドホルモン / 鉱質コルチコイド受容体 / 副腎ステロイド受容体
Outline of Research at the Start

脊椎動物のステロイドホルモン受容体は「ホルモン結合、受容体の二量体化、標的遺伝子との結合、補因子のリクルート、標的遺伝子の転写制御」という流れによって機能を発現する。本研究は女性ホルモンおよび副腎ステロイドの受容体のホルモン応答性に焦点を当て、キメラタンパク質の作成およびアミノ酸変異導入を利用して、動物種によるホルモン応答性の差異を明らかにし、「ステロイドホルモン受容体タンパク質の機能獲得の進化的プロセス」の解明を目指す。

Outline of Final Research Achievements

In this study, we succeeded in isolating glucocorticoid, mineralocorticoid, and progesterone receptor genes from the cartilaginous fish elephant shark. This result suggests that the adrenal steroid receptor and progesterone receptor possessed in higher vertebrates such as humans are already expressed from the evolutionary stage of cartilage fish. Next, these isolated receptors were used to investigate hormone responsiveness in detail. As a result, we found some differences between cartilaginous fish receptors and human receptors, and then we identified the causative site. By analyzing the function of steroid receptors in cartilaginous fish in this way, we were able to obtain some findings that lead to the functional evolution of the receptors.

Academic Significance and Societal Importance of the Research Achievements

本研究において、軟骨魚類であるゾウギンザメから糖質コルチコイド受容体、鉱質コルチコイド受容体、さらにプロゲステロン受容体遺伝子の単離に成功し、ホルモン応答性を詳細に調べた。ホルモン応答性の結果から、受容体のN末端領域の重要性を示唆するデータを得ることができた。これまで機能が不明だったN末端領域の機能解明につながる大きな学術的成果である。さらに、軟骨魚類のプロゲステロン受容体はヒトのプロゲステロン受容体のアンタゴニストであるミフェプリストンに反応しないことが判明した。この結果は、生殖医療への応用を視野に入れた新たな研究を進展させる基盤となることが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (18 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (5 results) Remarks (1 results)

  • [Int'l Joint Research] University of California, San Diego(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of California, San Diego/St. Could State University(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of California, San Diego/St. Cloud State University(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Aldosterone and dexamethasone activate African lungfish mineralocorticoid receptor: Increased activation after removal of the amino-terminal domain2022

    • Author(s)
      Katsu Yoshinao、Oana Shin、Lin Xiaozhi、Hyodo Susumu、Baker Michael E.
    • Journal Title

      The Journal of Steroid Biochemistry and Molecular Biology

      Volume: 215 Pages: 106024-106024

    • DOI

      10.1016/j.jsbmb.2021.106024

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] N-terminal domain regulates steroid activation of elephant shark glucocorticoid and mineralocorticoid receptors2021

    • Author(s)
      Katsu Yoshinao、Shariful Islam M.D.、Lin Xiaozhi、Takagi Wataru、Urushitani Hiroshi、Kohno Satomi、Hyodo Susumu、Baker Michael E.
    • Journal Title

      The Journal of Steroid Biochemistry and Molecular Biology

      Volume: 210 Pages: 105845-105845

    • DOI

      10.1016/j.jsbmb.2021.105845

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Diversification of mineralocorticoid receptor genes in a subterranean rodent, the naked mole-rat2021

    • Author(s)
      Oka Kaori、Bono Hidemasa、Kuroiwa Asato、Fujioka Shusuke、Shimizu Atsushi、Katsu Yoshinao、Miura Kyoko
    • Journal Title

      Journal of Molecular Endocrinology

      Volume: 66 Pages: 299-311

    • DOI

      10.1530/jme-20-0325

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation by Progestins, Corticosteroids, and RU486 of Transcriptional Activation of Elephant Shark and Human Progesterone Receptors: An Evolutionary Perspective2021

    • Author(s)
      Lin Xiaozhi、Takagi Wataru、Hyodo Susumu、Ijiri Shigeho、Katsu Yoshinao、Baker Michael E.
    • Journal Title

      ACS Pharmacology & Translational Science

      Volume: 5 Issue: 2 Pages: 52-61

    • DOI

      10.1021/acsptsci.1c00191

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Oil dispersant Corexit 9500 is weakly estrogenic, but does not skew the sex ratio in Alligator mississippiensis.2020

    • Author(s)
      McNabb NA, Bernhard MC, Brunell A, Lowers RH, Katsu Y, Spyropoulos DD, Kohno S
    • Journal Title

      Journal of Applied Toxicology

      Volume: 40 Issue: 2 Pages: 245-256

    • DOI

      10.1002/jat.3900

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Progesterone: An enigmatic ligand for the mineralocorticoid receptor.2020

    • Author(s)
      Baker ME, Katsu Y
    • Journal Title

      Biochemical Pharmacology

      Volume: 177 Pages: 113976-113976

    • DOI

      10.1016/j.bcp.2020.113976

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Transcriptional activation of elephant shark mineralocorticoid receptor by corticosteroids, progesterone, and spironolactone.2019

    • Author(s)
      Katsu Y, Kohno S, Oka K, Lin X, Otake S, Pillai NE, Takagi W, Hyodo S, Venkatesh B, Baker ME
    • Journal Title

      Science Signaling

      Volume: 12 Issue: 584 Pages: 1-10

    • DOI

      10.1126/scisignal.aar2668

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Evolution of the mineralocorticoid receptor.2019

    • Author(s)
      Baker ME, Katsu Y
    • Journal Title

      Vitamins and Hormones

      Volume: 109 Pages: 17-36

    • DOI

      10.1016/bs.vh.2018.10.009

    • ISBN
      9780128177822
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ミネラルコルチコイド受容体の分子進化2019

    • Author(s)
      勝 義直、Xiaozhi Lin, Michael E. Baker
    • Journal Title

      循環器内科

      Volume: 86 Pages: 215-222

    • NAID

      40022007887

    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] プロゲステロン受容体の11-デオキシコルチゾール結合のin vitroおよびin silico解析2021

    • Author(s)
      林 暁智・兵藤 晋・勝 義直
    • Organizer
      日本動物学会第92回大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ハイギョミネラルコルチコイド受容体の構造解析2021

    • Author(s)
      小穴進・兵藤晋・勝義直
    • Organizer
      日本動物学会第92回大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ゾウギンザメのプロゲステロン受容体の生理的リガンドの研究2020

    • Author(s)
      林 暁智・兵藤 晋・勝 義直
    • Organizer
      日本動物学会
    • Related Report
      2020 Research-status Report
  • [Presentation] ヌタウナギのプロゲステロン受容体とコルチコステロン受容体の単離と機能解析2019

    • Author(s)
      陳 澤・林 暁智・勝 義直
    • Organizer
      日本動物学会
    • Related Report
      2019 Research-status Report
  • [Presentation] ゾウギンザメのプロゲステロン受容体のヘリックス3―ヘリックス5の相互作用の研究2019

    • Author(s)
      林 暁智・兵藤 晋・勝 義直
    • Organizer
      日本動物学会
    • Related Report
      2019 Research-status Report
  • [Remarks] 北海道大学 生殖発生生物学講座1b

    • URL

      https://www.repdev-katsu.jp/index.html

    • Related Report
      2021 Annual Research Report 2020 Research-status Report 2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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