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Mechanism of differentiation of fetal Leydig cells by active and suppressive types of nuclear receptors

Research Project

Project/Area Number 16H05142
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionKyushu University

Principal Investigator

MOROHASHI Ken-ichirou  九州大学, 大学院医学研究院, 主幹教授 (30183114)

Research Collaborator Inoue Miki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords胎仔精巣 / ライディッヒ細胞 / Ad4BP / Tmsb10 / DHH / ステロイド / 代謝 / 核内受容体 / 精巣 / 細胞分化 / 遺伝子 / 転写因子
Outline of Final Research Achievements

Differentiation of Leydig cells that produce testosterone (androgen) in the testis is regulated by transcription factors such as Ad4BP/SF-1 and growth factors such as DHH. However, the mechanisms for Leydig cell differentiation by these factors remains unclear. In the present study, we newly identified Tmsb10 by a single cell transcriptome study. This factor was demonstrated to work in the process of Leydig cell differentiation from DHH stimulation to enhanced expression of Ad4BP.

Academic Significance and Societal Importance of the Research Achievements

ライディッヒ細胞の分化に不可欠な転写因子や細胞増殖因子は知られていたが、これらの知見は遺伝子ノックアウトの解析から得られた成果であった。そのため、これらの因子がどのようなメカニズムでライディッヒ細胞を分化させるかは不明であった。本研究は、この点に踏み込むことでライディッヒ細胞の分化メカニズムの理解へ向けた成果となった。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (31 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 10 results,  Acknowledgement Compliant: 3 results) Presentation (15 results) (of which Int'l Joint Research: 7 results,  Invited: 10 results) Remarks (2 results)

  • [Int'l Joint Research] KIST(韓国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] KAIST(韓国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] 成功大学(台湾)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Mouse polycomb group gene Cbx2 promotes osteoblastic but suppresses adipogenic differentiation in postnatal long bones2019

    • Author(s)
      Katoh-Fukui Yuko、Baba Takashi、Sato Tetsuya、Otake Hiroyuki、Nagakui-Noguchi Yuko、Shindo Miyuki、Suyama Mikita、Ohkawa Yasuyuki、Tsumura Hideki、Morohashi Ken-ichirou、Fukami Maki
    • Journal Title

      Bone

      Volume: 120 Pages: 219-231

    • DOI

      10.1016/j.bone.2018.10.021

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three population of adult Leydig cells in mouse testes revealed by a novel mouse HSD3BI-specific rat monoclonal antibody2019

    • Author(s)
      Chikako Yokoyama, Yuta Chigi, Takashi Baba, Atsushi Ohshitanai, Yumi Harada, Fumiya Tahahashi, Ken-ichirou Morohashi
    • Journal Title

      BBRC

      Volume: 511 Issue: 4 Pages: 916-920

    • DOI

      10.1016/j.bbrc.2019.02.100

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ad4BP/SF-1 regulates cholesterol synthesis to boost the production of steroids2018

    • Author(s)
      Takashi Baba, Hiroyuki Otake, Miki Inoue, Tetsuya Sato, Yasuhiro Ishihara, Ju-Yeon Moon, Megumi Tsuchiya, Kanako Miyabayashi, Hidesato Ogawa, Yuichi Shima, Lixiang Wang, Ryuichiro Sato, Takeshi Yamazaki, Mikita Suyama, Masatoshi Nomura, Man Ho Choi, Yasuyuki Ohkawa & Ken-ichirou Morohashi
    • Journal Title

      Communications Biology

      Volume: 1 Issue: 1 Pages: 1-9

    • DOI

      10.1038/s42003-018-0020-z

    • NAID

      120006799378

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PKA signalling drives zonal conversion within adult adrenocortical lineage in a sexually dimorphic manner2018

    • Author(s)
      Typhanie Dumontet, Isabelle Sahut-Barnola, Amandine Septier, Nathanaelle Montanier, Ingrid Plotton, Florence Roucher-Boulez, Veronique Ducros, Anne-Marie Lefrancois-Martinez, Jean-Christophe Pointud, Mohamad Zubair, Ken-ichirou Morohashi, David Breault, Pierre Val, Antoine Martinez
    • Journal Title

      JCI insight

      Volume: 3 Issue: 2

    • DOI

      10.1172/jci.insight.98394

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recent progress in understanding the mechanisms of Leydig cell differentiation2018

    • Author(s)
      Miki Inoue, Takashi Baba, and Ken-ichirou Morohashi
    • Journal Title

      Mol Cell Endocrinol

      Volume: 468 Pages: 39-46

    • DOI

      10.1016/j.mce.2017.12.013

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lysosomal activity maintains glycolysis and cyclin E1 expression by mediating Ad4BP/SF-1 stability for proper steroidogenic cell growth2017

    • Author(s)
      Syu JS, Baba T, Huang JY, Ogawa H, Hsieh CH, Hu JX, Chen TY, Lin TC, Tsuchiya M, Morohashi K, Huang BM, Lu FI
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 240-240

    • DOI

      10.1038/s41598-017-00393-4

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Alterations in fetal Leydig cell gene expression during fetal and adult development2017

    • Author(s)
      Kanako Miyabayashi, Yuichi Shima, Miki Inoue, Tetsuya Sato, Takashi Baba Yasuyuki Ohkawa, Mikita Suyama, Ken-ichirou Morohashi
    • Journal Title

      Sexual Development

      Volume: 11 Issue: 2 Pages: 53-63

    • DOI

      10.1159/000453323

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential lactate and cholesterol synthetic activities in XY and XX Sertoli cells.2017

    • Author(s)
      Shishido Y, Baba T, Sato T, Shima Y, Miyabayashi K, Inoue M, Akiyama H, Kimura H, Kanal Y, Ishihara Y, Haraguchi S, Miyazaki A, Rozman D, Yamazaki T, Choi MH, Ohkawa Y, Suyama M, Morohashi KI
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 41912-41912

    • DOI

      10.1038/srep41912

    • NAID

      120006799381

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of Ad4BP/SF-1 in regulating NADPH production in Y-1 cells2017

    • Author(s)
      Bing Li, Takashi Baba, Kanako Miyabayashi, Tetsuya Sato, Yuichi Shima, Daisuke Miura, Yasuyuki Ohkawa, Mikita Suyama, and Ken-ichirou Morohashi
    • Journal Title

      Endocrine J

      Volume: 64 Pages: 315-324

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] solation and characterization of mouse fetal Leydig progenitor cells2016

    • Author(s)
      Miki Inoue, Yuichi Shima, Kanako Miyabayashi, Tetsuya Sato, Takashi Baba, Yasuyuki Ohkawa, Haruhiko Akiyama, Mikita Suyama, Ken-ichirou Morohashi
    • Journal Title

      Endocrinology

      Volume: 157 Issue: 3 Pages: 1222-1233

    • DOI

      10.1210/en.2015-1773

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Neuregulin 1 regulates proliferation of leydig cells to support spermatogenesis and sexual behavior in adult mice2016

    • Author(s)
      Umehara T, Kawashima I, Kawai T, Hoshino Y, Morohashi KI, Shima Y, Richards JS, Shimada M
    • Journal Title

      Endocrinology

      Volume: 157 Issue: 12 Pages: 4899-4913

    • DOI

      10.1210/en.2016-1478

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Ad4BP/SF-1 more than a regulator of adrenal steroids2019

    • Author(s)
      Ken Morohashi, Miki Inoue, Takashi Baba
    • Organizer
      34th Joint Annual Conference of Biomedical Sciences
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Ad4BP/SF-1 more than a regulator of adrenal steroids2018

    • Author(s)
      Ken Morohashi
    • Organizer
      18th International Congress of Endocrinology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Orchestration of housekeeping and cell-specific metabolisms in steroidogenic cells by a transcription factor Ad4BP/SF-12018

    • Author(s)
      Ken Morohashi
    • Organizer
      The 18th Japan-Italy Symposium The front line of research into gender science
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ORCHESTRATION OF HOUSEKEEPING AND CELL-SPECIFIC METABOLISM FOR STEROID HORMONE SYNTHESIS BY A SINGLE TRANSCRIPTION FACTOR, Ad4BP/SF-1.2018

    • Author(s)
      Takashi Baba, Hiroyuki Otake, Miki Inoue, Kanako Miyabayashi, Yuichi Shima, Tetsuya Sato, Yasuyuki Ohkawa, Mikita Suyama, Ken-ichirou Morohashi.
    • Organizer
      8th International Symposium on the Biology of Vertebrate Sex Determination
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ad4BP/SF-1 regulates differentiation and metabolic activation in fetal Leydig cells2018

    • Author(s)
      Miki Inoue, Takashi Baba, Ken-ichirou Morohashi
    • Organizer
      8th International Symposium on the Biology of Vertebrate Sex Determination
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Genetic and Endocrine Regulation of of Gonadal Sex2017

    • Author(s)
      Ken-ichirou Morohashi
    • Organizer
      The 18th Congress of the International Society for Gender Medicine
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] History of fetal Leydig cells2017

    • Author(s)
      Ken-ichirou Morohashi
    • Organizer
      ENDO 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Ad4BPを介した細胞分化と代謝の強調的な遺伝子発現制御2017

    • Author(s)
      井上 実紀、馬場 崇、諸橋 憲一郎
    • Organizer
      第90回日本内分泌学会学術総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 核内受容体Ad4BP/SF-1によるステロイドホルモン産生へ向けた全プロセスの制御2017

    • Author(s)
      馬場 崇、Man Ho Choi、諸橋 憲一郎
    • Organizer
      生命科学系学会合同年次大会 ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 核内受容体Ad4BP/SF-1によるNADPH産生制御2017

    • Author(s)
      馬場 崇、Bing Li、諸橋 憲一郎
    • Organizer
      第25回日本ステロイドホルモン学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 核内受容体Ad4BP/SF-1によるステロイドホルモン産生の統括的制御2017

    • Author(s)
      馬場崇, 大竹博之, 井上実紀, 佐藤哲也, 石原康宏, 宮林香奈子, 嶋雄一, 山崎岳, 須山幹太, Choi Man-Ho, 大川恭行, 諸橋憲一郎
    • Organizer
      第21回日本生殖内分泌学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2016 Annual Research Report
  • [Presentation] 性差構築のメカニズム 胎仔ライディッヒ細胞の変遷2016

    • Author(s)
      諸橋 憲一郎
    • Organizer
      小児内分泌学会
    • Place of Presentation
      東京
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 哺乳類における精巣間質細胞の分化システム2016

    • Author(s)
      嶋雄一, 宮林香奈子, 井上実紀, 馬場崇、諸橋憲一郎
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 副腎皮質・生殖腺の代謝とAd4BP2016

    • Author(s)
      諸橋憲一郎、井上実紀、馬場崇
    • Organizer
      第24回日本ステロイドホルモン学会学術集会
    • Place of Presentation
      大分
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 栄養・代謝と性2016

    • Author(s)
      馬場崇、井上実紀、諸橋憲一郎
    • Organizer
      第89回日本内分泌学会学術総会
    • Place of Presentation
      大阪
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Remarks]

    • Related Report
      2018 Annual Research Report
  • [Remarks]

    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2022-08-05  

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