11β-hydroxysteroid dehydrogenaseの局所化 - ミネラロコルチコイド受容体の組織特異的保護物質
C R Edwards1, P M Stewart, D Burt
1Department of Medicine, Western General Hospital, Edinburgh, UK.
Lancet (London, England)
|October 29, 1988
まとめ
ミネラルコルチコイド受容体は,選択性組織における11β-ヒドロキシステロイド脱水素酶 (11β-OHSD) によってコルチコステロンから保護されます. この酵素は,
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.
- 生理学 生理学とは
背景:
- ミネラルコルチコイド受容体 (MR) は,アルドステロンとコルチゾールにインビトロで非特異的結合を示す.
- In vivoでは,アルドステロンに対する組織選択性は,MRの非特異性にもかかわらず存在します.
- この選択性は,腎臓や腺のような組織で観察されるが,ヒポカンプスや心臓では観察されない.
研究 の 目的:
- 特定の組織におけるアルドステロン選択性の背後にあるメカニズムを調査する.
- 11β-ヒドロキシステロイド脱水素酶 (11β-OHSD) がMRの活性を調節する役割を決定する.
- 11β-OHSD欠乏または抑制の生理学的結果を説明する.
主な方法:
- 実験はネズミで行われました.
- 11β-OHSDの組織濃度は,選択的および非選択的組織で測定されました.
- 酵素阻害後の受容体結合を評価するために,autoradiographic研究が行われました.
主要な成果:
- 11β-ヒドロキシステロイド脱水素酶 (11β-OHSD) は,アルドステロン選択性組織におけるより高い濃度で発見されました.
- 酵素の局所化は,コルチコステロンに対するパラクリンまたはオトクリン保護機構を示唆しています.
- 11β-OHSDの阻害は,コルチコステロンとアルドステロンの類似の結合部位で,保護の喪失につながりました.
結論:
- 11β-ヒドロキシステロイド脱水素酶 (11β-OHSD) は,コルチコステロンを代謝することによって,特定の組織にアルドステロンの選択性を授与する.
- この酵素活性は,ミネラルコルチコイド受容体をコルチコステロンによる飽和から保護する.
- この発見は,11β-OHSD欠乏症や甘草の摂取に関連した高血圧や低血量症などの症状を説明しています.
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