Development of plasma steroid precursor-based new differential diagnosis and molecular targeted therapies for hyperaldosteronism

2014 Fiscal Year Final Research Report

• Project/Area Number: 26670174
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Human pathology
• Research Institution: Kyoto University
• Principal Investigator: MASAO Doi 京都大学, 薬学研究科(研究院), 准教授 (20432578)
• 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)
• Research Collaborator: OTA Takumi ; YARIMIZU Daisuke ; NAKAGAWA Yuuki
• Project Period (FY): 2014-04-01 – 2015-03-31
• Keywords: アルドステロン / 副腎

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.

Free Research Field

内分泌