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Alterations in the cutaneous steroid hormone environment with aging and their involvement in skin diseases in the elderly

Research Project

Project/Area Number 19K09033
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionShowa University

Principal Investigator

Haraguchi Shogo  昭和大学, 医学部, 講師 (20592132)

Co-Investigator(Kenkyū-buntansha) スルチョードリ ビシュワジット  九州大学, 基幹教育院, 准教授 (00535453)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsステロイド / 皮膚 / 毛包幹細胞 / 皮脂腺 / 加齢 / テストステロン / アンドロゲン受容体 / 毛乳頭 / 脱毛 / エストラジオール / hsd17b3 / 亜鉛 / 老化
Outline of Research at the Start

加齢に伴う性腺機能の低下により、血中の性ステロイドレベルが低下し、男性・女性ともに更年期障害が引き起こされる。そこで、ホルモン補充療法が実施されるが、その効果・作用機序には不明瞭な点も多い。
研究代表者は加齢時の皮膚において網羅的にホルモン分泌の変動を解析し、加齢時に増加するホルモンを見出した。そこで、このホルモンが加齢時の皮膚においてどの様な作用を持つのか、また、高齢者の皮膚疾患に関わるのかを明らかにすることを目指す。

Outline of Final Research Achievements

The sex steroid synthesis system exists not only in the gonads and adrenal glands, but also in the skin, where it cooperates with steroids derived from the gonads and adrenal glands to precisely regulate skin function. Aging-related hypogonadism causes a decrease in blood sex steroid levels, resulting in menopause. However, it is not well understood how the cutaneous steroidogenesis system changes with aging.
In this study, we analyzed the skin steroidogenesis system in old age and found that the decline in gonadal function with aging causes an excess of the skin steroidogenesis system, which may be a factor in causing age-related skin diseases.

Academic Significance and Societal Importance of the Research Achievements

本邦は既に超高齢社会にあるが、人口動態などを考慮すると今後も当面は超高齢社会にあるのは避けられない。また、高齢化は先進国では一様に進行しており、現在高齢者と定義されている年代が、今後より一層、社会活動に参画することは活力ある社会の維持には不可欠である。そのためには健康寿命の延伸が不可欠であり、健康寿命の延伸には老化の理解とその医療への応用が不可欠である。本研究成果は、加齢時に全身性の変化を引き起こす血中性ホルモンの減少に起因する皮膚症状の理解に資するものであり、今後は本研究成果を発展させることで高齢者特有の疾患に対する治療への応用が期待できる。

Report

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

Research Products

(29 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (17 results) (of which Int'l Joint Research: 15 results,  Peer Reviewed: 17 results,  Open Access: 11 results) Presentation (8 results) (of which Invited: 4 results) Book (1 results)

  • [Int'l Joint Research] Dessau Medical Center//Brandenburg Medical School(ドイツ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Dessau Medical Center/Brandenburg Medical School(ドイツ)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Dessau Medical Center/Brandenburg Medical School-/Theodor Fontane(ドイツ)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Calpain-mediated proteolytic production of free amino acids in vascular endothelial cells augments obesity-induced hepatic steatosis.2022

    • Author(s)
      Risako Akasu, Takuro Miyazaki, Mohamed Z Elhussiny, Yuki Sugiura, Yuki Tomitsuka, Shogo Haraguchi, Kinya Otsu, Vishwajit S Chowdhury, Akira Miyazaki
    • Journal Title

      Journal of Biological Chemistry

      Volume: N/A Pages: 101953-101953

    • DOI

      10.1016/j.jbc.2022.101953

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction2022

    • Author(s)
      Sasaki L*, Hamada Y*, Yarimizu D*, (20 people), Miyake T, Doi M# * : co-first, # : corresponding
    • Journal Title

      Nature Aging

      Volume: 2 Pages: 105-114

    • DOI

      10.1038/s43587-021-00167-8

    • NAID

      120007191374

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oral Administration of L-Citrulline Changes Brain Free Amino Acid and Monoamine Metabolism in Heat-Exposed Broiler Chickens2022

    • Author(s)
      Chowdhury Vishwajit S.、Han Guofeng、Elhussiny Mohamed Z.、Ouchi Yoshimitsu、Tran Phuong V.、Nishimura Haruka、Haraguchi Shogo、Cockrem John F.、Bungo Takashi、Furuse Mitsuhiro
    • Journal Title

      Frontiers in Animal Science

      Volume: 3 Pages: 875572-875572

    • DOI

      10.3389/fanim.2022.875572

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Central Taurine Attenuates Hyperthermia and Isolation Stress Behaviors Augmented by Corticotropin-Releasing Factor with Modifying Brain Amino Acid Metabolism in Neonatal Chicks2022

    • Author(s)
      Elhussiny Mohamed Z.、Tran Phuong V.、Tsuru Yuriko、Haraguchi Shogo、Gilbert Elizabeth R.、Cline Mark A.、Bungo Takashi、Furuse Mitsuhiro、Chowdhury Vishwajit S.
    • Journal Title

      Metabolites

      Volume: 12 Pages: 83-83

    • DOI

      10.3390/metabo12010083

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Adult‐onset hypothyroidism causes mechanical hypersensitivity due to peripheral nerve hyperexcitability based on voltage‐gated potassium channel downregulation in male mice2022

    • Author(s)
      Suda Machiko、Takatsuru Yusuke、Amano Izuki、Haraguchi Shogo、Koibuchi Noriyuki
    • Journal Title

      J Neurosci Res.

      Volume: 100 Pages: 506-511

    • DOI

      10.1002/jnr.25001

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Liver metabolomic analysis in broiler chicks: Profiling the metabolites after oral administration of <scp>l</scp> ‐citrulline2021

    • Author(s)
      Chowdhury Vishwajit S.、Ouchi Yoshimitsu、Haraguchi Shogo、Bungo Takashi
    • Journal Title

      Animal Science Journal

      Volume: 92

    • DOI

      10.1111/asj.13609

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Oral administration of L‐citrulline changes the concentrations of plasma hormones and biochemical profile in heat‐exposed broilers2021

    • Author(s)
      Chowdhury Vishwajit S.、Ouchi Yoshimitsu、Han Guofeng、Eltahan Hatem M.、Haraguchi Shogo、Miyazaki Takuro、Shiraishi Jun‐ichi、Sugino Toshihisa、Bungo Takashi
    • Journal Title

      Animal Science Journal

      Volume: 92

    • DOI

      10.1111/asj.13578

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Potential role of amino acids in the adaptation of chicks and market-age broilers to heat stress.2021

    • Author(s)
      Chowdhury VS, Han G, Eltahan HM, Haraguchi S, Gilbert ER, Cline MA, Cockrem JF, Bungo T, Furuse M.
    • Journal Title

      Frontiers in Veterinary Science

      Volume: 7 Pages: 610541-610541

    • DOI

      10.3389/fvets.2020.610541

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Central GABAA receptor mediates taurine-induced hypothermia and possibly reduces food intake in thermo-neutral chicks and regulates plasma metabolites in heat-exposed chicks2021

    • Author(s)
      Elhussiny Mohamed Z.、Tran Phuong V.、Pham Cuong V.、Nguyen Linh T.N.、Haraguchi Shogo、Gilbert Elizabeth R.、Cline Mark A.、Bungo Takashi、Furuse Mitsuhiro、Chowdhury Vishwajit S.
    • Journal Title

      J. Therm. Biol.

      Volume: 98 Pages: 102905-102905

    • DOI

      10.1016/j.jtherbio.2021.102905

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hic-5 is required for activation of pancreatic stellate cells and development of pancreatic fibrosis in chronic pancreatitis2020

    • Author(s)
      Gao Lin、Lei Xiao-Feng、Miyauchi Aya、Noguchi Masahito、Omoto Tomokatsu、Haraguchi Shogo、Miyazaki Takuro、Miyazaki Akira、Kim-Kaneyama Joo-ri
    • Journal Title

      Sci Rep.

      Volume: 10 Pages: 19105-19105

    • DOI

      10.1038/s41598-020-76095-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pineal Neurosteroids: Biosynthesis and Physiological Functions2020

    • Author(s)
      Haraguchi Shogo、Tsutsui Kazuyoshi
    • Journal Title

      Front Endocrinol.

      Volume: 11 Pages: 549-549

    • DOI

      10.3389/fendo.2020.00549

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of l-leucine in ovo feeding on thermotolerance, growth and amino acid metabolism under heat stress in broilers2020

    • Author(s)
      Han G.、Ouchi Y.、Hirota T.、Haraguchi S.、Miyazaki T.、Arakawa T.、Masuhara N.、Mizunoya W.、Tatsumi R.、Tashiro K.、Bungo T.、Furuse M.、Chowdhury V. S.
    • Journal Title

      Animal

      Volume: - Pages: 1701-1709

    • DOI

      10.1017/s1751731120000464

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neuroprotective actions of cerebellar and pineal allopregnanolone on Purkinje cells2020

    • Author(s)
      Tsutsui Kazuyoshi、Haraguchi Shogo
    • Journal Title

      FASEB BioAdvances

      Volume: 2 Pages: 149-159

    • DOI

      10.1096/fba.2019-00055

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms2019

    • Author(s)
      Haraguchi S, Kamata M, Tokita T, Tashiro KI, Sato M, Nozaki M, Okamoto-Katsuyama M, Shimizu I, Han G, Chowdhury VS, Lei XF, Miyazaki T, Kim-Kaneyama JR, Nakamachi T, Matsuda K, Ohtaki H, Tokumoto T, Tachibana T, Miyazaki A, Tsutsui K.
    • Journal Title

      Elife

      Volume: 8

    • DOI

      10.7554/elife.45306

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Alleviation of murine osteoarthritis by deletion of the focal adhesion mechanosensitive adapter, Hic-52019

    • Author(s)
      Miyauchi Aya、Kim-Kaneyama Joo-ri、Lei Xiao-Feng、Chang Song Ho、Saito Taku、Haraguchi Shogo、Miyazaki Takuro、Miyazaki Akira
    • Journal Title

      Sci Rep.

      Volume: 9 Pages: 15770-15770

    • DOI

      10.1038/s41598-019-52301-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] L-Leucine increases the daily body temperature and affords thermotolerance in broiler chicks.2019

    • Author(s)
      Han G, Yang H, Wang Y, Haraguchi S, Miyazaki T, Bungo T, Tashiro K, Furuse M, Chowdhury VS
    • Journal Title

      Asian-Australasian Journal of Animal Sciences

      Volume: in press Pages: 842-848

    • DOI

      10.5713/ajas.18.0677

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pineal allopregnanolone saves cerebellar Purkinje cells from apoptosis2019

    • Author(s)
      Haraguchi Shogo
    • Journal Title

      Electrophoresis Letters

      Volume: 63 Issue: 1 Pages: 19-23

    • DOI

      10.2198/electroph.63.19

    • NAID

      130007638631

    • ISSN
      2189-2628, 2189-2636
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 加齢に伴う皮膚ステロイドホルモン環境の変化とその皮膚疾患への関与2021

    • Author(s)
      原口省吾
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 光環境が発達期の脳に与える影響2021

    • Author(s)
      原口省吾
    • Organizer
      第47回日本神経内分泌学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 皮膚バリアを制御する皮脂腺の新たな働き2021

    • Author(s)
      原口省吾, 大滝博和, 杉浦悠毅, 原田一貴, 坪井貴司
    • Organizer
      日本動物学会第92回大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] The effect of nighttime lighting on brain development and its molecular mechanism2020

    • Author(s)
      原口省吾
    • Organizer
      第126回日本解剖学会総会・全国学術集会 / 第98回日本生理学会大会 合同大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 加齢に伴う皮膚ステロイド産生系の亢進はタンパク質品質管理機構の異常を引き起こす2019

    • Author(s)
      原口省吾, 大滝博和, 杉浦悠毅, 嶋雄一, 宮崎章
    • Organizer
      第27回日本ステロイドホルモン学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 松果体アロプレグナノロンはPACAP発現を促すことで小脳プルキンエ細胞の細胞死を抑制する2019

    • Author(s)
      原口省吾, スルチョードリ ビシュワジット, 中町智哉, 松田恒平, 徳元俊伸, 橘哲也, 宮崎章, 筒井和義
    • Organizer
      第90回日本動物学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 加齢に伴う皮膚ステロイド産生系の変容が老人性脱毛症の発症に関わる2019

    • Author(s)
      原口省吾, 大滝博和, 杉浦悠毅, 嶋雄一, 宮崎章
    • Organizer
      第37回内分泌代謝学サマーセミナー
    • Related Report
      2019 Research-status Report
  • [Presentation] 加齢に伴う皮膚ステロイド産生系の変容とその皮膚疾患発症への影響2019

    • Author(s)
      原口省吾, 杉浦悠毅, 杉山栄二, 嶋雄一, 宮崎章
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Book] Neurosteroids. In: Handbook of Hormones, 2nd Edition.pp 955-9662021

    • Author(s)
      Tsutsui K, Haraguchi S
    • Total Pages
      1113
    • Publisher
      ACADEMIC PRESS, INC.
    • ISBN
      9780128206492
    • Related Report
      2021 Annual Research Report

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

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