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妊娠によって活性化された孤児核受容体は,新しいステロイドシグナル伝達経路を定義します
S A Kliewer1, J T Moore, L Wade
1Department of Molecular Endocrinology, Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA.
Cell
|March 7, 1998
まとめ
研究者は,様々なステロイドによって活性化される新しい核受容体であるプレグナンX受容体 (PXR) を発見しました. PXRは,ステロイドホルモンとステロールのホメオスタシスに影響を与え,新しいシグナル伝達経路を示唆しています.
科学分野:
- エンドクリノロジー エンドクリノロジー
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- ステロイドホルモンは,核受容体を通して重要な細胞プロセスを調節する.
- 新しい核受容体の理解は,複雑なシグナル伝達経路の解読の鍵です.
研究 の 目的:
- ステロイドホルモンの作用に関与する新しい孤児核受容体を特定し,特徴づけること.
- この新しい受容体の活性化と機能的影響を調査する.
主な方法:
- 新型の孤児核受容体,プレグナンX受容体 (PXR) の特定.
- 天然および合成ステロイドによるPXR活性化の分析.
- PXRイソフォーム特異的活性化 (PXR.1およびPXR.2) の検査
- プレグネノロン16α-カルボニトリルのPXR.1および下流の遺伝子発現に対する影響の評価.
主要な成果:
- 妊娠中のX受容体 (PXR) の発見,妊娠中ホルモンやプロゲステロンを含む様々なステロイドによって活性化.
- 異なるステロイド活性化による2つのPXR同型 (PXR.1とPXR.2) の特定.
- Pregnenolone 16alpha-carbonitrileは選択的にPXR.1を活性化し,CYP3Aステロイドヒドロキシラゼを誘導する.
- PXRがステロールと胆酸のバイオシンセシスを調節する証拠 in vivo.
結論:
- 妊娠前X受容体 (PXR) は,ステロイドホルモンシグナル伝達を媒介する新しい核受容体を表します.
- PXRは,ステロイドホルモンとステロールのホメオスタシスを調節する役割を果たします.
- この発見は,代謝調節における新しい経路を理解するための道を開きます.
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