帕拉本在抑制人类和老鼠淋巴腺3β-hydroxysteroid脱酶的结构性决定因素
Chentao Ding1, He Zhu1, Yunbing Tang2
1Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital, Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Toxicology and applied pharmacology
|October 25, 2024
概括
这项研究表明, parabens 抑制了人类和老鼠的淋巴腺3β-基固醇脱酶 (3β-HSD) 和孕激素分泌. 烯的功效取决于疏水性和碳链长度.
科学领域:
- 内分泌学和生殖毒理学
- 生物化学和分子生物学
背景情况:
- 烯是广泛使用的防腐剂,具有潜在的内分泌干扰作用.
- 3β-基类固醇脱酶 (3β-HSD) 对于类固醇激素的合成至关重要.
- 了解帕拉本与3β-HSD相互作用对于评估生殖健康风险至关重要.
研究的目的:
- 为了研究10个类甲对人类和老鼠淋巴体3β-HSD活性的影响.
- 评估 parabens 对人类细胞中孕激素分泌的影响.
- 为了比较人类和老鼠模型之间的 parabens 的抑制功效.
主要方法:
- 使用人类KGN细胞和老鼠丸显微体进行酶活性测定.
- 在KGN细胞中测量孕激素分泌量.
- 分子对接,双变量相关性和3D-QSAR分析以阐明机制.
主要成果:
- 乙基,基,丁基,基,基,基,非基,基和基 parabens 作为混合抑制剂抑制了人类的3β-HSD2 (IC50: 4.15139.96 μM) 和老鼠的3β-HSD1 (IC50: 7.15110.76 μM).
- 大多数类甲会显著抑制KGN细胞中的孕激素分泌.
- 抑制功效与LogP,分子量,重原子数和碳数相反相关;非类是最强大的抑制剂.
结论:
- 几种类型的对人类和老鼠的淋巴体3β-HSD活性表现出抑制作用.
- 烯的疏水性和碳链长度显著调节它们的抑制作用.
- 这些发现突出了通过3β-HSD抑制暴露在帕拉本对生殖健康的潜在风险.
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