Development of plasma steroid precursor-based new differential diagnosis and molecular targeted therapies for hyperaldosteronism
| Project/Area Number |
26670174
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Human pathology
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| Research Institution | Kyoto University |
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Principal Investigator |
MASAO Doi 京都大学, 薬学研究科(研究院), 准教授 (20432578)
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| Co-Investigator(Renkei-kenkyūsha) |
OKAMURA Hitoshi 京都大学, 大学院薬学研究科, 教授 (60158813)
FUSTIN Jean-Michel 京都大学, 大学院薬学研究科, 特定講師 (50711818)
SASANO Hironobu 東北大学, 医学部, 教授 (50187142)
NAKAMURA Yasuhiro 東北大学, 医学部, 准教授 (80396499)
SATO Fumitoshi 東北大学, 医学部, 講師 (70343051)
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| Research Collaborator |
OTA Takumi
YARIMIZU Daisuke
NAKAGAWA Yuuki
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| Project Period (FY) |
2014-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | アルドステロン / 副腎 / ステロイド合成酵素 |
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| Outline of Final Research Achievements |
We previously showed that the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD) is involved in the development of primary aldosteronism (PA) in mice (Nat Med 2010) and found that this enzyme is indeed inappropriately expressed in the lesions of PA in humans (JCEM 2014). Here we measured plasma concentrations of steroid precursors and demonstrated that adrenal vein samples from PA patients exhibit a significant increase in 3β-HSD enzymatic activity, compared with that of contralateral, nondiseased adrenal glands. These data clearly show that enhanced activity of 3β-HSD is involved in human PA pathology. We also revealed that angiotensin II can stimulate expression of this enzyme through de novo protein synthesis of the orphan nuclear receptor NGFIB (Mol Cell Biol 2014). Thus, 3β-HSD appears to play a key role in the regulation of aldosterone synthesis in normal physiology and pathophysiology.
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Report
(2 results)
Research Products
(27 results)
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[Journal Article] 3ß-hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma2015
Author(s)
Konosu-Fukaya S, Nakamura Y, Satoh F, Ono Y, Felizola SJ, Ise K, Maekawa T, Takeda K, Katsu K, Fujishima F, Kasajima A, Watanabe M, Arai Y, Gomez-Sanchez EP, Gomez-Sanchez CE, Doi M, Okamura H, and Sasano H
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Journal Title
Mol. Cell. Endocrinol.
Volume: 印刷中
Pages: 205-212
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Steroidogenic enzymes, their related transcription factors and nuclear receptors in human sebaceous glands under normal and pathological conditions2014
Author(s)
Azmahani A, Nakamura Y, Felizola SJ, Ozawa Y, Ise K, Inoue T, McNamara KM, Doi M, Okamura H, Zouboulis CC, Aiba S, and Sasano H
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Journal Title
J. Steroid Biochem. Mol. Biol.
Volume: 144
Pages: 268-279
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Isoform-specific monoclonal antibodies against 3beta-hydroxysteroid dehy drogenase/isomerase family provide markers for subclassification of hum an primary aldosteronism. .2014
Author(s)
Doi M, Satoh F, Maekawa T, N akamura Y, Fustin JM, Tainaka M, Hotta Y, Takahashi Y, Morimoto R, Takase K, Ito S, Sasano H, and Okamura H
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Journal Title
J Clin Endocrinol Metab
Volume: 99
Issue: 2
Pages: 257-62
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Immunolocalization of murine type VI 3β-hydroxysteroid dehydrogenase in the adrenal gland, testis, skin, and placenta2014
Author(s)
Koki Yamamura, Magao Doi, Hida Hayashi, Takumi Ota, Iori Murai, Yunhong Hotta, Rie Komatsu, Hitoshi Okamura
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Journal Title
Molecular and Cellular Endocrinology
Volume: 382
Issue: 1
Pages: 131-138
DOI
Related Report
Peer Reviewed
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