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Action of starfish gonadotropic hormone: interaction with the receptor and mechanism of gamete shedding

Research Project

Project/Area Number 19K06747
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 InstitutionShowa University

Principal Investigator

MITA Masatoshi  昭和大学, 医学部, 客員教授 (50190674)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords生殖腺刺激ホルモン / リラキシン様生殖巣刺激ペプチド / G-タンパク質共役受容体 / 生殖制御機構 / ヒトデ / リラキシン様生殖腺刺激ペプチド / 免疫組織化学染色 / C末アミド化ペプチド / Gタンパク質共役受容体 / 免疫組織化学 / シグナル伝達 / アセチルコリン
Outline of Research at the Start

生殖腺刺激ホルモン(GTH)は脊椎動物ばかりでなく無脊椎動物においても生殖細胞の形成や成長・成熟に重要な働きを持つ。ヒトデのGTHは放射神経に存在し、リラキシンとよく似た2本鎖ペプチドから構成されるペプチドホルモンである。それ故、ヒトデのGTHをリラキシン様生殖腺刺激ペプチド (relaxin-like gonad-stimulating peptide, RGP)と呼ぶ。本研究は、ヒトデをモデルに生殖制御機構を分子レベルで解明することを目的として、RGP受容体を同定し、RGPと受容体との相互作用の解析を行い、さらに、これまでほとんど未解決であった放卵・放精のメカニズムについて解析する。

Outline of Final Research Achievements

Orthologs of relaxin-like gonadotrophic peptides (RGPs) were identified or predicted from 24 species of starfish. Some RGPs were chemically synthesized and examined spawning-inducing activities. RGP receptors (RGPRs) were also identified in Patiria pectinifera. The GPCRs were G protein-coupled receptors. Immunohistochemical analysis using anti-RGP antibodies revealed that RGP existed not only in the radial nerve cords and circumoral nerve rings but also in the terminal tentacles and gonoducts. Acetylcholine (ACh) was found within ovaries and testes. Thus presumably, RGP secreted from gonoducts stimulates ovarian follicle cells or interstitial cells, to produce maturation-inducing hormone, 1-methyladenine, resulting oocyte maturation and ACh secretion to shed mature eggs or spermatozoa.

Academic Significance and Societal Importance of the Research Achievements

ヒトデのRGPは無脊椎動物で世界で最初に同定された生殖腺刺激ホルモン様活性物質でヒトの妊娠期の女性ホルモンとして知られるリラキシンとよく似た2本鎖ペプチドである。最近、RGPはヒトデ以外の他の棘皮動物(ナマコ類やクモヒトデ類)においても生殖腺刺激ホルモン様活性を持つことが明らかになった。さらにショウジョウバエの生殖巣の発達にリラキシン様ペプチド(Dilp8)とその受容体(Lgr3)が制御していることが示されている。それ故、本研究の成果は、ヒトデの生殖研究分野に新たな研究基盤を確立したばかりでなく、新口動物と旧口動物にまたがるリラキシン様ペプチドとその受容体の分子共進化を知る切っ掛けとなった。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (39 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 5 results) Presentation (20 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] Queen Mary University of London(英国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Queen Mary University of London(英国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Queen Mary University of London(英国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Queen Mary University of London(英国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] A Relaxin-Like Gonad-Stimulating Peptide Appears in the Early Development of the Starfish Patiria pectinifera2023

    • Author(s)
      Mita Masatoshi、Katayama Hidekazu、Yamamoto Kazutoshi、Shibata Yasushi、Kiyomoto Masato
    • Journal Title

      Zoological Science

      Volume: 40 Issue: 1 Pages: 7

    • DOI

      10.2108/zs220058

    • URL

      https://pure.teikyo.jp/en/publications/fbf818a8-1c7e-43f7-aa1e-dd529ec931c6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The C-terminally amidated relaxin-like gonad-stimulating peptide in the starfish Astropecten scoparius2023

    • Author(s)
      Katayama Hidekazu、Mita Masatoshi
    • Journal Title

      General and Comparative Endocrinology

      Volume: 334 Pages: 114226-114226

    • DOI

      10.1016/j.ygcen.2023.114226

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization and localization of relaxin-like gonad-stimulating peptide in the crown-of-thorns starfish, Acanthaster cf. solaris2022

    • Author(s)
      Mita Masatoshi、Osugi Tomohiro、Kawada Tsuyoshi、Satake Honoo、Katayama Hidekazu、Kitamura Takaya、Miura Takeshi、Miura Chiemi
    • Journal Title

      General and Comparative Endocrinology

      Volume: 328 Pages: 114107-114107

    • DOI

      10.1016/j.ygcen.2022.114107

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A specific and sensitive enzyme-linked immunosorbent assay for measurement of relaxin-like gonad-stimulating peptide in the starfish Asterias rubens2021

    • Author(s)
      Mita Masatoshi、Elphick Maurice R.、Katayama Hidekazu
    • Journal Title

      General and Comparative Endocrinology

      Volume: 310 Pages: 113831-113831

    • DOI

      10.1016/j.ygcen.2021.113831

    • URL

      https://pure.teikyo.jp/en/publications/67310248-d818-4625-a007-ab2c8a6d1fa8

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Starvation causes female-to-male sex reversal through lipid metabolism in the teleost fish, medaka (Olyzias latipes)2020

    • Author(s)
      Sakae Yuta、Oikawa Akira、Sugiura Yuki、Mita Masatoshi、Nakamura Shuhei、Nishimura Toshiya、Suematsu Makoto、Tanaka Minoru
    • Journal Title

      Biology Open

      Volume: 9 Issue: 4 Pages: 1-12

    • DOI

      10.1242/bio.050054

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipid composition of gametes in scleractinian reef-building corals: wax-esters generate buoyancy for the gametes2020

    • Author(s)
      Okubo Nami、Nakano Yoshikatsu、Mita Masatoshi
    • Journal Title

      Invertebrate Reproduction & Development

      Volume: 64 Issue: 4 Pages: 291-295

    • DOI

      10.1080/07924259.2020.1815875

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel G protein-coupled receptor for starfish gonadotropic hormone, relaxin-like gonad-stimulating peptide2020

    • Author(s)
      Mita Masatoshi、Matsubara Shin、Osugi Tomohiro、Shiraishi Akira、Wada Azumi、Satake Honoo
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 11 Pages: 0242877-0242877

    • DOI

      10.1371/journal.pone.0242877

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A relaxin-like gonad-stimulating peptide identified from the starfish Astropecten scoparius2020

    • Author(s)
      Mita Masatoshi、Osugi Tomohiro、Matsubara Shin、Kawada Tsuyoshi、Satake Honoo、Katayama Hidekazu
    • Journal Title

      Molecular Reproduction and Development

      Volume: 88 Issue: 1 Pages: 34

    • DOI

      10.1002/mrd.23444

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ヒトデの配偶子放出のメカニズム:ヒトデの放卵・放精はアセチルコリンによるCa2+-influxにより誘起される2020

    • Author(s)
      三田雅敏, 大杉知宏, 高橋俊雄, 渡辺健宏, 佐竹 炎
    • Journal Title

      比較内分泌学

      Volume: 46 Pages: 79-81

    • NAID

      130007854007

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of chimeric relaxin-like gonad-stimulating peptides on oocyte maturation and ovulation in the starfish Asterias rubens and Aphelasterias japonica2020

    • Author(s)
      Mita Masatoshi、Elphick Maurice R.、Katayama Hidekazu
    • Journal Title

      General and Comparative Endocrinology

      Volume: 287 Pages: 113351-113351

    • DOI

      10.1016/j.ygcen.2019.113351

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mechanism of gamete shedding in starfish: Involvement of acetylcholine in extracellular Ca2+-dependent contraction of gonadal walls2020

    • Author(s)
      Mita Masatoshi、Osugi Tomohiro、Takahashi Toshio、Watanabe Takehiro、Satake Honoo
    • Journal Title

      General and Comparative Endocrinology

      Volume: 290 Pages: 113401-113401

    • DOI

      10.1016/j.ygcen.2020.113401

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel approach for preparing disulfide-rich peptide-KLH conjugate applicable to the antibody production2019

    • Author(s)
      Katayama Hidekazu、Mizuno Ryo、Mita Masatoshi
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 83 Issue: 10 Pages: 1791

    • DOI

      10.1080/09168451.2019.1618696

    • URL

      https://pure.teikyo.jp/en/publications/e887db41-d536-4ae8-953a-2833a32a1b98

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interaction of starfish gonadotropin with its receptor: Effect of chimeric relaxin-like gonad-stimulating peptides2019

    • Author(s)
      Mita Masatoshi、Nakamura Keitaro、Tsutsui Kazuyoshi、Katayama Hidekazu
    • Journal Title

      General and Comparative Endocrinology

      Volume: 276 Pages: 30

    • DOI

      10.1016/j.ygcen.2019.02.019

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Starfish Gonadotropic Hormone: From Gamete-Shedding Substance to Relaxin-Like Gonad-Stimulating Peptide2019

    • Author(s)
      Mita Masatoshi
    • Journal Title

      Frontiers in Endocrinology

      Volume: 10 Pages: 182-182

    • DOI

      10.3389/fendo.2019.00182

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Localisation of relaxin-like gonad-stimulating peptide expression in starfish: are the gonoducts the physiological source for its role as a regulator of spawning?2022

    • Author(s)
      Feng, Y.L., Pinon Gonzalez, V.M., Lin, M., Egertova, M., Mita, M., and Elphick, M.R.
    • Organizer
      30th Conference of the European Society for Comparative Endocrinology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Relaxin-like gonad-stimulating peptide family in asteroidea2022

    • Author(s)
      Mita, M.
    • Organizer
      30th Conference of the European Society for Comparative Endocrinology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization and localization of relaxin-like gonad-stimulating peptide in the crown-of-thorns starfish, Acanthaster cf. solaris2022

    • Author(s)
      Mita, M., Osugi, T., Tsuyoshi Kawada, T., Satake, H., Katayama, H., Kitamura, T., Miura, T., Miura, C.
    • Organizer
      日本動物学会 第93回
    • Related Report
      2022 Annual Research Report
  • [Presentation] Discovery of a second relaxin-like gonadotropic peptide in starfish2022

    • Author(s)
      Mita, M., Katayama, H., Feng, Y., Pinon Gonzalez, V.M., Miyazaki, A., Elphick, M.R.
    • Organizer
      The 95th Annual Meeting of the Japanese Biochemical Society
    • Related Report
      2022 Annual Research Report
  • [Presentation] Identification of sources of relaxin-like gonad-stimulating peptide as a regulator of spawning in starfish.2021

    • Author(s)
      Feng, Y.L., Pinon Gonzalez, V.M., Egertova M., Mita, M., Elphick, M.R.
    • Organizer
      The sixth meeting of the North American Society for Comparative Endocrinology
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規に同定したヒトデのリラキシン様生殖腺刺激ペプチド(RGP)受容体について2021

    • Author(s)
      三田雅敏, 松原 伸, 大杉知裕, 白石 慧, 和田明澄, 佐竹 炎
    • Organizer
      第92回日本動物学会オンライン米子大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Structural characterization of relaxin-like gonad-stimulating peptide from the starfish Astropecten scoparius2021

    • Author(s)
      Katayama Hidekazu, Mita Masatoshi
    • Organizer
      The 58th Japanese Peptide Symposium, Online conference
    • Related Report
      2021 Research-status Report
  • [Presentation] 新規に同定したリラキシン様生殖腺刺激ペプチド(RGP)のC末端アミド化の可能性2021

    • Author(s)
      三田雅敏,宮崎 章, 片山秀和
    • Organizer
      第94回日本生化学会
    • Related Report
      2021 Research-status Report
  • [Presentation] オニヒトデ生殖腺刺激ペプチド(RGP)の特徴と分布2021

    • Author(s)
      三田雅敏, 大杉知裕, 松原 伸, 川田剛士, 佐竹 炎, 片山秀和, 喜多村鷹也, 三浦 猛, 三浦智恵美
    • Organizer
      第45回日本比較内分泌学会およびシンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] ヒトデ類におけるリラキシン様生殖腺刺激ペプチド(RGP)の系統学的解析2020

    • Author(s)
      三田雅敏
    • Organizer
      第91回日本動物学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 抗原用リラキシン様生殖腺刺激ペプチド(RGP)の化学合成とELISAによる定量方法の開発2020

    • Author(s)
      三田雅敏,Maurice R. Elphick, 宮崎 章, 片山秀和
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] 無脊椎動物における最初の生殖腺刺激ホルモン: ヒトデのリラキシン様生殖腺刺激ペプチド2019

    • Author(s)
      三田雅敏
    • Organizer
      日本動物学第90回大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] マヒトデ目ヒトデの放卵活性に対するリラキシン様生殖腺刺激ペプチド(RGP)誘導体の影響2019

    • Author(s)
      三田雅敏, Maurice R. Elphick, 片山秀和
    • Organizer
      日本動物学第90回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] イトマキヒトデにおけるリラキシン様生殖腺刺激ペプチドの幼生での発現2019

    • Author(s)
      清本正人, 三田雅敏
    • Organizer
      日本動物学第90回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 生殖巣に存在する内因性アセチルコリンの排卵誘起作用について2019

    • Author(s)
      三田雅敏,大杉知裕, 高橋俊雄, 宮崎 章, 佐竹 炎
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Starfish spawning induced by non-neuronal acetylcholine within gonads2019

    • Author(s)
      Mita, M., Osugi, T., Takahashi, T., Satake, H.
    • Organizer
      The 5th Biennial Conference of the North American Society for Comparative Endocrinology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Metabolic regulation of sex differentiation under starvation in medaka2019

    • Author(s)
      Sakae, Y., Sugiura, Y., Oikawa, A., Mita, M., Nishimura, T., Tanaka, M.
    • Organizer
      Society for the Study of Reproduction 52nd Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] メダカ性分化におけるパントテン酸代謝の関与2019

    • Author(s)
      榮 雄大, 杉浦 悠毅, 及川 彰, 三田 雅敏, 西村 俊哉, 田中 実
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] ELISAによるマヒトデ生殖腺刺激ホルモン(RGP)の定量法2019

    • Author(s)
      三田雅敏,大杉知裕, 高橋俊雄, 宮崎 章, 佐竹 炎
    • Organizer
      第44回日本比較内分泌学会およびシンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] パントテン酸代謝抑制がメダカ性転換をもたらす2019

    • Author(s)
      榮 雄大, 杉浦 悠毅, 及川 彰, 三田 雅敏, 西村 俊哉, 田中 実
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/bio_mita

    • Related Report
      2022 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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