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Regulation of sexually dimorphic functions of adrenal cortex by sex chromosomes

Research Project

Project/Area Number 20H03436
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionKyushu University

Principal Investigator

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

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2022: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywords性差 / 副腎皮質 / 糖質コルチコイド / Ad4BP / ヒストン脱メチル化酵素 / 骨格筋 / トランスクリプトーム / ヒストン脱メチル化
Outline of Research at the Start

我々の体を構成する全ての細胞は性を有する。本研究ではこの性が性ホルモンと性染色体によって構築されることを示すことを目的とする。そこで、明瞭な構造的かつ質的性差を示すと期待されるマウス副腎皮質を実験対象とし、雌雄のトランスクリプトームの取得、遺伝子発現に対する性ホルモンの影響、性染色体にコードされる4種類のヒストン脱メチル化遺伝子の性差構築への関与について検討する。また、4種類のヒストン脱メチル化遺伝子とヒストンの修飾状態を明らかにする。これらの検討を行うことで、細胞の性が性ホルモンと性染色体によって構築されることを示す。

Outline of Final Research Achievements

Comparing gene expressions of adrenal cortices between male and female reveals that gene expressions in female are totally higher than those of male by 1.8-fold in average. Genes whose expression is highly female-biased (higher than the average) were examined. Consequently, these genes were found to be functionally related to energy metabolism and glucocorticoid synthesis. Indeed, cellular activities corresponding to those processes were higher in female. Target genes of Ad4BP, an essential transcription factor for adrenocortical differentiation, were searched. As the consequence, nearly half of the genes expressed were found to be potential targets of Ad4BP. Finally, we examined the effects of the sexually dimorphic adrenal cortex on the size of skeletal muscles and showed that sexually different amount of glucocorticoid gives a certain effect on sexually differential size of the skeletal muscles.

Academic Significance and Societal Importance of the Research Achievements

一般に性差は性ホルモンよって作り出されると考えられてきた。したがって男性ホルモンとその受容体の直接的な影響が調べられてきた。本研究では副腎皮質細胞のRNA量、そして遺伝子発現が雌雄で異なることを示した。このような全遺伝子の発現の差が性差の基盤となっていることを示した初めての例であり、性差を問うにあたって着目すべき新たな視点を提供した。また、副腎皮質で合成される糖質コルチコイドによる誘導は骨格筋に限ったことではなく全身に影響が及ぶと推測される。したがって、糖質コルチコイド活性を有する薬剤を使用する場合には、種々の細胞の性差の変化という観点に注意すべきであると考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (27 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (13 results) (of which Int'l Joint Research: 1 results,  Invited: 6 results) Book (1 results) Remarks (2 results)

  • [Int'l Joint Research] KIST(韓国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Prostaglandin E2 receptor Ptger4b regulates female-specific peptidergic neurons and female sexual receptivity in medaka2022

    • Author(s)
      Fleming Thomas、Kikuchi Yukiko、Nakajo Mikoto、Tachizawa Masaya、Inazumi Tomoaki、Tsuchiya Soken、Sugimoto Yukihiko、Saito Daisuke、Suyama Mikita、Ohkawa Yasuyuki、Baba Takashi、Morohashi Ken-ichirou、Okubo Kataaki
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 1215-1215

    • DOI

      10.1038/s42003-022-04195-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tmsb10 triggers fetal Leydig differentiation by suppressing the RAS/ERK pathway.2022

    • Author(s)
      Miki Inoue, Takashi Baba, Fumiya Takahashi, Miho Terao, Shogo Yanai, Yuichi Shima, Daisuke Saito, Kei Sugihara, Takashi Miura, Shuji Takada, Mikita Suyama, Yasuyuki Ohkawa, Ken-Ichirou Morohashi.
    • Journal Title

      Commun Biol.

      Volume: 5 Issue: 1 Pages: 974-974

    • DOI

      10.1038/s42003-022-03941-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intrauterine hyponutrition reduces fetal testosterone production and postnatal sperm count in the mouse.2022

    • Author(s)
      Fujisawa Y, Ono H, Konno A, Yao I, Itoh H, Baba T, Morohashi K, Katoh-Fukui Y, Miyado M, Fukami M and Ogata T.
    • Journal Title

      Journal of the Endocrine Society

      Volume: 6 Issue: 4 Pages: 1-11

    • DOI

      10.1210/jendso/bvac022

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sex differences in metabolic pathways are regulated by Pfkfb3 and Pdk4 expression in rodent muscle.2021

    • Author(s)
      Christianto A, Baba T, Takahashi F, Inui K, Inoue M, Suyama M, Ono Y, Ohkawa Y, Morohashi KI.
    • Journal Title

      Commun Biol.

      Volume: 4 Issue: 1 Pages: 1264-1264

    • DOI

      10.1038/s42003-021-02790-y

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of ovarian follicles from mouse pluripotent stem cells2021

    • Author(s)
      Yoshino Takashi、Suzuki Takahiro、Nagamatsu Go、Yabukami Haruka、Ikegaya Mika、Kishima Mami、Kita Haruka、Imamura Takuya、Nakashima Kinichi、Nishinakamura Ryuichi、Tachibana Makoto、Inoue Miki、Shima Yuichi、Morohashi Ken-ichirou、Hayashi Katsuhiko
    • Journal Title

      Science

      Volume: 373 Issue: 6552 Pages: 282-289

    • DOI

      10.1126/science.abe0237

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] VCAM1-a4b1 integrin interaction mediates interstitial tissue reconstruction in 3-D re-aggregate culture of dissociated prepubertal mouse testicular cells2021

    • Author(s)
      Abe K, Kon S, Kameyama H, Zhang J, Morohashi K, Shimamura K, Abe S-I
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 18332-18332

    • DOI

      10.1038/s41598-021-97729-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Eicosapentaenoic acid changes muscle transcriptome and intervenes in aging-related fiber type transition in male mice2021

    • Author(s)
      Yamazaki Hiroki、Nishimura Mayu、Uehara Masaaki、Kuribara-Souta Akiko、Yamamoto Motohisa、Yoshikawa Noritada、Morohashi Ken-Ichirou、Tanaka Hirotoshi
    • Journal Title

      American Journal of Physiology-Endocrinology and Metabolism

      Volume: 320 Issue: 2 Pages: E346-E358

    • DOI

      10.1152/ajpendo.00184.2020

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene expression and functional abnormalities in XX/Sry Leydig cells2021

    • Author(s)
      Yanai Shogo、Baba Takashi、Inui Kai、Miyabayashi Kanako、Han Soyun、Inoue Miki、Takahashi Fumiya、Kanai Yoshiakira、Ohkawa Yasuyuki、Choi Man Ho、Morohashi Ken-ichirou
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 719-719

    • DOI

      10.1038/s41598-020-80741-z

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GC‐MS‐based metabolic signatures reveal comparative steroidogenic pathways between fetal and adult mouse testes2020

    • Author(s)
      Han Soyun、Baba Takashi、Yanai Shogo、Byun Dong Jun、Morohashi Ken‐ichirou、Kim Jae‐Hong、Choi Man Ho
    • Journal Title

      Andrology

      Volume: 9 Issue: 1 Pages: 400-406

    • DOI

      10.1111/andr.12893

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Coordination of Multiple Cellular Processes by NR5A1/Nr5a12020

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

      Endocrinology and Metabolism

      Volume: 35 Issue: 4 Pages: 756-764

    • DOI

      10.3803/enm.2020.402

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Ad4BPは almightyか?2023

    • Author(s)
      諸橋 憲一郎
    • Organizer
      第30回日本ステロイドホルモン学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] オスの骨格筋はおにぎりが好きで、メスの骨格筋は霜降りの肉が好き2022

    • Author(s)
      諸橋憲一郎
    • Organizer
      自然科学研究機構シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] The new perspective of the NR5A1/Ad4BP role for the Adrenal Function.2022

    • Author(s)
      Ken-ichirou Morohashi
    • Organizer
      The 12th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Society
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨格筋サイズは副腎の性差に依存する2022

    • Author(s)
      高橋史也, 馬場崇, Christianto Antonius, 柳井翔吾, 石渡 啓介, 中林 一彦, 秦 健一郎, 菊水健史, 諸橋憲一郎
    • Organizer
      第45回 日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Ad4BPはステロイド産生細胞のマスター遺伝子か?2021

    • Author(s)
      諸橋憲一郎
    • Organizer
      第94回日本内分泌学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Male-preferred glycolysis and female-preferred fatty acid utilization of skeletal muscle bestowed by Pfkfb3 and Pdk42021

    • Author(s)
      Antonius Christianto, Takashi Baba, Fumiya Takahashi, Kai Inui, Miki Inoue, Mikita Suyama, Yusuke Ono, Yasuyuki Ohkawa, Morohashi Ken-ichirou
    • Organizer
      第44回日本分子生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Y染色体にコードされる脱メチル化酵素UTYは精巣ライディッヒ細胞における初期応答系遺伝子群の発現をヒストン脱メチル化活性を介さずに制御する2021

    • Author(s)
      柳井 翔吾、馬場 崇、井上 実紀、高橋 史也、寺尾 美穂、高田 修治、石渡 啓介、中林 一彦、秦 健一郎、金井 克晃、諸橋 憲一郎
    • Organizer
      第44回日本分子生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] TMSB10 regulates fetal Leydig cell differentiation by activation of Hedgehog signal.2021

    • Author(s)
      Miki Inoue, Takashi Baba, Fumiya Takahashi, Miho Terao, Shuji Takada, Ken-ichirou Morohashi
    • Organizer
      第44回日本分子生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Ad4BP/SF-1の発現量の性差によって誘導される細胞内代謝の性差2021

    • Author(s)
      高橋史也、馬場崇、Christianto Antonius、柳井翔吾、石渡 啓介、中林 一彦、秦 健一郎、諸橋憲一郎
    • Organizer
      第44回日本分子生物学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 細胞の性2020

    • Author(s)
      諸橋憲一郎、馬場崇
    • Organizer
      第93回日本内分泌学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ライディッヒ細胞の発生分化2020

    • Author(s)
      馬場崇、井上実紀、諸橋憲一郎
    • Organizer
      第93回日本内分泌学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] XX/Sryオスマウスのライディッヒ細胞における遺伝子発現と精巣内ステロイドホルモン量の網羅的解析2020

    • Author(s)
      柳井翔吾、馬場崇、宮林香奈子、Soyun Han、井上実紀、高橋史也、金井克晃、大川恭行、Man-Ho Choi、諸橋憲一郎
    • Organizer
      第28回ステロイドホルモン学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Sex chromosome composition affects gene expression and function in Leydig cells2020

    • Author(s)
      Yanai S, Baba T, Inui K, Miyabayashi K, Han S, Inoue M, Takahashi F, Kanai Y, Ohkawa Y, Choi MH, Morohashi KI.
    • Organizer
      第43回日本分子生物学会
    • Related Report
      2020 Annual Research Report
  • [Book] オスとな何で、メスとは何か?2022

    • Author(s)
      諸橋 憲一郎
    • Total Pages
      212
    • Publisher
      NHK出版
    • Related Report
      2022 Annual Research Report
  • [Remarks] 九州大学 大学院医学研究院 分子生命科学系部門 性差生物学講座(分子生物学)ホームページ

    • URL

      https://www.med.kyushu-u.ac.jp/seisaseibutu/

    • Related Report
      2022 Annual Research Report 2020 Annual Research Report
  • [Remarks] 科研費 新学術領域研究 平成29-33年度 性スペクトラムー連続する表現型としての雌雄ーホームページ

    • URL

      http://park.itc.u-tokyo.ac.jp/sexspectrum/

    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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