2016 Fiscal Year Final Research Report
Chemical screening for steroidogenic differentiation of human iPSC-derived intermediate mesoderm cells.
Project/Area Number |
26461380
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Endocrinology
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Research Institution | Kyoto University |
Principal Investigator |
SONE Masakatsu 京都大学, 医学研究科, 特定准教授 (40437207)
|
Co-Investigator(Kenkyū-buntansha) |
田浦 大輔 京都大学, 医学研究科, 特定助教 (10558612)
|
Research Collaborator |
OSAFUNE Kenji
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Keywords | ステロイドホルモン / 副腎皮質 / 性腺 / 発生分化 |
Outline of Final Research Achievements |
We tried to elucidate the steroidogenic differentiation processes using hiPSC-derived intermediate mesoderm (IM) that is known to be the origin of the human adrenal cortex and gonads. We first performed chemical screening to identify small molecules that induce steroidogenic differentiation of IM cells expressing OSR1, an early IM marker. We identified cabergoline as an inducer of 3β-HSD2, an essential enzyme for steroidogenesis. Although cabergoline is a potent dopamine D2 receptor agonist, additional experiments showed that cabergoline exerted effects as a low-affinity agonist of D1 receptors. Further analysis of OSR1+ cells transfected with SF-1/Ad4BP revealed that D1 receptor agonist upregulated expression of various steroidogenic enzymes and increased secretion of steroid hormones. These results suggest the importance of dopamine D1 receptor signalling in steroidogenic differentiation, which contributes to effective induction of steroidogenic cells from hiPSCs.
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Free Research Field |
内分泌学
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