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在性激素治疗期间,揭示了功能变化的潜在机制
Sarah A van Eeghen1,2,3, Laura Pyle4,5, Phoom Narongkiatikhun4,6
1Center of Expertise on Gender Dysphoria, Department of Internal Medicine, Amsterdam UMC, Location VU University, Amsterdam, Netherlands.
The Journal of clinical investigation
|April 7, 2025
概括
性激素显著影响脏健康. 雌激醇对功能和管状健康产生保护作用,而则表现出相反的作用,突出显示了慢性病中性别特异精准医学的潜力.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 内分泌学 在内分泌学.
- 蛋白质组学是指蛋白质组学.
背景情况:
- 与女性相比,患有慢性病 (CKD) 的男性表现出加速的功能下降.
- 性激素与此有关,女性化疗法增加,男性化疗法降低估计的淋巴细胞过率 (eGFR).
- 性激素对测量GFR (mGFR), perfusion,管状功能和分子机制的特定影响仍然基本上没有被描述.
研究的目的:
- 研究女性化 (雌激醇和抗雄激素) 和男性化 () 激素治疗对CKD患者脏生理学的影响.
- 探索对测量的GFR (mGFR), perfusion,管状损伤生物标志物和血蛋白质组形状的影响.
- 阐明导致性激素对功能和CKD性二态变异的分子机制.
主要方法:
- 一项前性观察性研究,涉及开始女性化 (n=23) 或男性化 (n=21) 治疗的个体.
- 评估基线和3个月的mGFR (iohexol清除率), perfusion (para-aminohippuric acid清除率) 和尿管损伤生物标志物.
- 血蛋白质组学分析以确定差异表达的蛋白质及其与激素水平和功能相关的关系.
主要成果:
- 雌性化疗法增加了mGFR (+3.6%) 和 perfusion (+9.1%),但没有改变淋巴球压力. 观察到管状损伤生物标志物 (例如,YKL-40,EGF,MCP-1) 的显著减少.
- 雄性化治疗没有显示mGFR或输液的显著变化,但尿液YKL-40 (+134%) 和血TNFR-1 (+8%) 的增加.
- 蛋白质组分析揭示了不同的蛋白质表达模式:女性化治疗中的49种蛋白质和男性化治疗中的356种蛋白质. 保护脏的蛋白质与雌激醇正相关,与丸激素负相关.
结论:
- 性激素对脏生理有很大的影响,雌醇对球和管状功能具有保护作用.
- 丸激素似乎对脏健康主要有相反的影响.
- 这些发现强调了性激素在功能性二态化中的作用,并表明在治疗慢性病时,有潜在的性别特异精确医学策略.
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