葡萄皮质类药物,它们的用途,性二态和疾病:新的概念,机制和发现
Genesee J Martinez1, Malik Appleton1, Zachary A Kipp1
1Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, United States.
Physiological reviews
|September 21, 2023
概括
葡萄糖皮质类药物对应激反应和炎症至关重要,具有两个受体异型 (GRα和GRβ). 了解它们的不同角色和性二态是改善疗法和预防耐药性的关键.
科学领域:
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 下垂体-垂体-上腺 (HPA) 轴通过皮质醇释放来调节压力反应.
- 葡萄糖皮质类药物对哺乳动物系统至关重要,合成形式治疗炎症性疾病.
- 葡萄糖皮质体受体 (GR) 信号传递涉及两个异构体:GRα (结合) 和GRβ (非结合).
研究的目的:
- 审查葡萄糖皮质体机制,重点关注GR异型及其对健康的影响.
- 分析慢性葡萄糖皮质激素治疗的影响和葡萄糖皮质激素耐药性的发展.
- 探索对葡萄糖皮质醇的性二态反应及其治疗后果.
主要方法:
- 关于葡萄糖皮质激素生理学和药理学的文献综述.
- 对GRα和GRβ异型函数和信号通路的批判性分析.
- 检查有关葡萄糖皮质醇诱导的副作用和耐药性的证据.
主要成果:
- 在HPA轴或GR异型表达中发生的干扰会导致严重的健康问题.
- 慢性葡萄糖皮质激素治疗可以诱导耐药性和副作用,如体重增加和糖尿病.
- 与男性相比,女性表现出更高反应度的HPA轴,表明性二态.
结论:
- 了解GR异型及其差异性作用对于有效的葡萄糖皮质激素治疗至关重要.
- 未来的治疗策略可能包括向两种GR异型,以防止耐药性和减轻副作用.
- 开发双GR异形激动剂可以提供一种新的方法来管理炎症性疾病和与压力相关的疾病.
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