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The novel mechanism of aldosterone production in aldosterone-producing adenoma

Research Project

Project/Area Number 26860707
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Endocrinology
Research InstitutionHiroshima University

Principal Investigator

OKI KENJI  広島大学, 病院(医), 病院助教 (30638995)

Research Collaborator Gomez-Sanchez Celso E.  University of Mississippi Medical Center
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords原発性アルドステロン症 / アルドステロン / G蛋白共役型受容体 / アルドステロン合成酵素 / 細胞内カルシウム伝達 / G蛋白共役受容体
Outline of Final Research Achievements

Microarray analysis targeting GPCR-associated genes was conducted using APA without known mutations (APA-WT) samples and APA with the KCNJ5 mutation (APA-KCNJ5). Gonadotropin-releasing hormone receptor (GNRHR) was the highest expression in APA-WT by microarray analysis. The quantitative polymerase chain reaction (qPCR) assay results revealed higher GNRHR expression levels in APA-WT samples those in APA-KCNJ5 samples. Patients with APA-WT (n=9), which showed higher GNRHR and LHCGR levels, had significantly higher GnRH-stimulated aldosterone response than those with APA-KCNJ5 (n=13) (P<0.05). HAC15 cells with KCNJ5 gene carrying T158A mutation exhibited a significantly lower GNRHR expression than that in control cells. We clarified increased expression of GNRHR and LHCGR in APA-WT, and the molecular analysis including the receptor expression associated with clinical findings of GnRH stimulation.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (26 results)

All 2017 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (5 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 4 results) Presentation (19 results) (of which Int'l Joint Research: 4 results)

  • [Int'l Joint Research] University of Mississippi Medical Center(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Mississippi Medical Center(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism2017

    • Author(s)
      Nishimoto, K., Koga, M., Seki, T., Oki, K., Gomez-Sanchez, E.P., Gomez-Sanchez, C.E., Naruse, M., Sakaguchi, T., Morita, S., Kosaka, T., Oya, M., Ogishima, T., Yasuda, M., Suematsu, M., Kabe, T., Omura, M., Nishikawa, T., Mukai, K.
    • Journal Title

      Mol. Cell. Endocrinol.

      Volume: 441 Pages: 124-133

    • DOI

      10.1016/j.mce.2016.10.014

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Gonadotropin-Releasing Hormone Stimulate Aldosterone Production in a Subset of Aldosterone-Producing Adenoma.2016

    • Author(s)
      Kishimoto R, Oki K, Yoneda M, Gomez-Sanchez CE, Ohno H, Kobuke K, Itcho K, Kohno N.
    • Journal Title

      Medicine (Baltimore)

      Volume: 95 Issue: 20 Pages: e3659-e3659

    • DOI

      10.1097/md.0000000000003659

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] YPEL4 modulates HAC15 adrenal cell proliferation and is associated with tumor diameter.2016

    • Author(s)
      Oki K, Plonczynski MW, Gomez-Sanchez EP, Gomez-Sanchez CE.
    • Journal Title

      Mol Cell Endocrinol

      Volume: 434 Pages: 93-98

    • DOI

      10.1016/j.mce.2016.06.022

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Hypothalamic-pituitary-adrenal axis activity is associated with the prevalence of chronic kidney disease in diabetic patients2016

    • Author(s)
      Asao T, Oki K, Yoneda M, Tanaka J, Kohno N.
    • Journal Title

      Endocrine Journal

      Volume: 63 Issue: 2 Pages: 119-126

    • DOI

      10.1507/endocrj.EJ15-0360

    • NAID

      130005127189

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hypomethylation of CYP11B2 in Aldosterone-Producing Adenoma.2016

    • Author(s)
      Yoshii Y, Oki K, Gomez-Sanchez CE, Ohno H, Itcho K, Kobuke K, Yoneda M.
    • Journal Title

      Hypertension

      Volume: 68 Issue: 6 Pages: 1432-1437

    • DOI

      10.1161/hypertensionaha.116.08313

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Ca2+ Binding Protein, Calneuron 1, Increased Ca2+ in Endoplasmic Reticulum and Aldosterone Production in Aldosterone-producing Adenoma2017

    • Author(s)
      Kazuhiro Kobuke, Kenji Oki, Celso E. Gomez-Sanchez, Elise P. Gomez-Sanchez, Kiyotaka Itcho, Yoko Yoshii, Haruya Ohno, Masayasu Yoneda
    • Organizer
      42nd Meeting of the International Aldosterone Conference
    • Place of Presentation
      Orlando, FL, USA
    • Year and Date
      2017-03-30
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The effects of Angiotensin II metabolites on aldosterone production in the HAC15 human adrenocortical cell line2017

    • Author(s)
      Yoko Yoshii, Kenji Oki, Kiyotaka Itcho, Kazuhiro Kobuke, Haruya Ohno, Masayasu Yoneda
    • Organizer
      42nd Meeting of the International Aldosterone Conference
    • Place of Presentation
      Orlando, FL, USA
    • Year and Date
      2017-03-30
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The regulation of PCP4 transcription via DNA methylation in aldosterone-producing adenoma2017

    • Author(s)
      Kiyotaka Itcho, Kenji Oki, Celso E. Gomez-Sanchez, Kazuhiro Kobuke, Yoko Yoshii, Haruya Ohno, Masayasu Yoneda
    • Organizer
      42nd Meeting of the International Aldosterone Conference
    • Place of Presentation
      Orlando, FL, USA
    • Year and Date
      2017-03-30
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アルドステロン合成に関わるエピジェネティック制御機構2016

    • Author(s)
      沖健司
    • 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
    • Year and Date
      2016-12-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] アンギオテンシンII代謝産物によるアルドステロン合成制御機構に関する検討2016

    • Author(s)
      一町澄宜,沖健司,吉井陽子,久保田益亘,江草玄太郎,小武家和博,大久保博史,大野晴也,米田真康
    • 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
    • Year and Date
      2016-12-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] APA及び遺伝子変異に基づくステロイド合成酵素のDNAメチル化解析2016

    • Author(s)
      吉井陽子、沖健司、一町澄宜、小武家和博、久保田益亘、大久保博史、大野晴也、米田真康
    • Organizer
      第26回臨床内分泌代謝Update
    • Place of Presentation
      大宮
    • Year and Date
      2016-11-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] 高ACTH血症下におけるアルドステロン動態を評価した一例2016

    • Author(s)
      一町澄宜、沖健司、吉井陽子、久保田益亘、江草玄太郎、小武家和博、大久保博史、大野晴也、米田真康
    • Organizer
      第26回臨床内分泌代謝Update
    • Place of Presentation
      大宮
    • Year and Date
      2016-11-18
    • Related Report
      2016 Annual Research Report
  • [Presentation] アルドステロン産生腺腫におけるステロイド合成酵素のエピジェネティック調節機構2016

    • Author(s)
      吉井陽子、沖健司、小武家和博、一町澄宣、大野晴也、米田真康
    • Organizer
      第39回日本高血圧学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-09-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] DNA hypo-methylation of Aldosterone synthesis (CYP11B2) in aldosterone producing adenoma, but not regulated by somatic mutations of adenoma.2016

    • Author(s)
      Yoko Yoshii, Kenji Oki, Celso E. Gomez-Sanchez, Haruya Ohno, Kiyotaka Itcho, Kazuhiro Kobuke, Masayasu Yoneda
    • Organizer
      International Society of Hypertension 2016 satellite symposium Renin-angiotensin-aldosterone system
    • Place of Presentation
      Tokyo
    • Year and Date
      2016-09-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 遺伝子変異を認めないアルドステロン産生腺腫におけるアルドステロン合成機構の探索2016

    • Author(s)
      一町澄宜、沖健司、小武家和博、吉井陽子、前田修作、大野晴也、米田真康、河野修興
    • Organizer
      第89回日本内分泌学会学術総会
    • Place of Presentation
      京都
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] アルドステロン産生腺腫におけるステロイド合成酵素のエピジェネティック調節機構2016

    • Author(s)
      吉井陽子、沖健司、小武家和博、一町澄宜、前田修作、大野晴也、米田真康、河野修興
    • Organizer
      第89回日本内分泌学会学術総会
    • Place of Presentation
      京都
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] アルドステロン産生腺腫におけるGNRHRを介したアルドステロン合成機構2016

    • Author(s)
      沖健司、一町澄宜、小武家和博、吉井陽子、前田修作、大野晴也、米田真康
    • Organizer
      第23回日本ステロイドホルモン学会学術集会
    • Place of Presentation
      岡山
    • Year and Date
      2016-01-15
    • Related Report
      2015 Research-status Report
  • [Presentation] The Relationship Between Tumor Genotype and Clinical or Pathological Characteristics in Patients with Aldosterone Producing Adenoma2015

    • Author(s)
      Kiyotaka Itcho, Kazuhiro Kobuke, Kenji Oki, Rui Kishimoto, Shusaku Maeda, Haruya Ohno, Masayasu Yoneda, Nobuoki Kohno
    • Organizer
      The Endocrine society's 96th Annual Meeting and Expo
    • Place of Presentation
      McCormick Place, Chicago, IL, USA
    • Year and Date
      2015-06-21 – 2015-06-24
    • Related Report
      2014 Research-status Report
  • [Presentation] The clinical and pathological characteristics of aldosterone producing adenoma with ATP1A1 mutation2015

    • Author(s)
      Kazuhiro Kobuke, Kiyotaka Itcho, Kenji Oki, Rui Kishimoto, Shusaku Maeda, Haruya Ohno, Masayasu Yoneda, Nobuoki Kohno
    • Organizer
      40th Meeting of the International Aldosterone Meeting
    • Place of Presentation
      The Westin Chicago River North, Chicago, IL, USA
    • Year and Date
      2015-06-19 – 2015-06-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 原発性アルドステロン症の一次スクリーニングにおけるアルドステロン絶対値の有効性2015

    • Author(s)
      沖 健司,小武家 和博,一町 澄宜,岸本 瑠衣,松本 武史,光波 直也,大久保 博史,前田 修作,大野 晴也,米田 真康,河野 修興
    • Organizer
      第3回臨床高血圧フォーラム
    • Place of Presentation
      広島,広島国際会議場
    • Year and Date
      2015-05-24 – 2015-05-26
    • Related Report
      2014 Research-status Report
  • [Presentation] CYP11B2抗体を用いたアルドステロン産生腺腫の免疫組織化学による検討2015

    • Author(s)
      小武家 和博,志和 亜華,沖 健司,米田 真康,粟屋 智一,中西 修平,河野 修興
    • Organizer
      第87回日本内分泌学会学術総会
    • Place of Presentation
      福岡,福岡国際会議場
    • Year and Date
      2015-04-24 – 2015-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] ATP1A1体細胞変異を有するアルドステロン産生腺腫の臨床的および病理学的検討2015

    • Author(s)
      一町 澄宜,沖 健司,小武家 和博,長野 学,毛利 麻衣子,志和 麻実,岸本 瑠衣,久保田 益亘,大久保 博史,前田 修作,大野 晴也,米田 真康,中西 修平,河野 修興
    • Organizer
      第87回日本内分泌学会学術総会
    • Place of Presentation
      福岡,福岡国際会議場
    • Year and Date
      2015-04-24 – 2015-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 副腎皮質細胞の増殖およびアルドステロン合成におけるYPEL4の役割2015

    • Author(s)
      沖 健司,Elise P Gomez-Sanchez, Celso E Gomez-Sanchez
    • Organizer
      第87回日本内分泌学会学術総会
    • Place of Presentation
      福岡,福岡国際会議場
    • Year and Date
      2015-04-24 – 2015-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] アンギオテンシンII代謝産物によるアルドステロン合成制御機構に関する検討2015

    • Author(s)
      一町澄宜、沖健司、小武家和博、岸本瑠衣、前田修作、大野晴也、米田真康、河野修興
    • Organizer
      第88回日本内分泌学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2015-04-23
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2022-02-16  

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