性激素在人类初级肝细胞中不同调节脂质代谢基因
Lena Seidemann1,2, Clara Paula Lippold1,2, Carolin Marie Rohm1,2
1Department of Hepatobiliary Surgery and Visceral Transplantation, Clinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, 04103, Leipzig, Germany.
BMC endocrine disorders
|August 1, 2024
概括
与代谢功能障碍相关的脂肪性肝病 (MASLD) 的性别差异受性激素的影响. 男性和女性肝细胞对激素的反应不同,影响脂质代谢基因表达.
科学领域:
- 肝病学和内分泌学.
- 分子生物学分子生物学
- 脂质代谢 脂质代谢是什么
背景情况:
- 与代谢功能障碍相关的脂肪性肝病 (MASLD) 在男性中比女性更为普遍.
- 生物性别和性激素的影响在当前的体外肝脏模型中表现不足.
- 了解性别特异性机制对于MASLD研究至关重要.
研究的目的:
- 研究人类初级肝细胞 (PHHs) 的性别特异性差异.
- 分析关键性激素对肝脂代谢基因表达的影响.
- 评估男性和女性PHH对荷尔蒙刺激的反应.
主要方法:
- 来自男性和女性捐赠者的初级人类肝细胞 (PHHs) 用17β-雌激醇,和孕激素进行培养.
- 使用RT-qPCR量化了8个脂质代谢基因的mRNA表达.
- 通过LC-MS分析了细胞培养超级生物中的性激素和代谢物.
主要成果:
- 观察到低密度脂蛋白受体 (LDLR) 的性别特异表达,男性PHHs的水平更高.
- PHHs代谢了所有测试的性激素.
- 对基因表达的荷尔蒙影响因肝细胞的性别而异,女性PHH对17β-雌激醇,和孕激素的反应不同,男性PHH对17β-雌激醇和的反应不同.
结论:
- 男性和女性PHHs表现出肝脂代谢基因的差异表达.
- 肝细胞根据细胞的性别对性激素的反应有所不同.
- 考虑细胞性对阐明MASLD病理生理学至关重要.
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