The Effects of Estrogen on Serum Level and Hepatocyte Expression of PCSK9
The Effects of Estrogen on Serum Level and Hepatocyte Expression of PCSK9
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雌激素对血清PCSK9水平及肝细胞表达的影响
DOI：
10.1016/j.metabol.2015.01.009
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发表时间：
2015-04-01
影响因子：
9.8
通讯作者：
Zhou, Hon Gwen
中科院分区：
文献类型：
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作者：
Guo, Wen;Fu, Jinxiang;Zhou, Hon Gwen
目标。我们以前报道过，在中国汉族人群中，绝经后妇女的血清PCSK9水平高于绝经前妇女。这种差异是否与雌激素有关还没有得到很好的描述。本研究旨在探讨雌激素水平的变化是否与血清PCSK9浓度的变化有关。采用双抗体夹心ELISA法测定了727例26~85岁健康女性的血清PCSK9水平。还对这些人进行了人体测量和生化检查，如雌激素和血脂。接下来，我们测定了30名健康育龄妇女(24-26岁)月经周期的血清PCSK9和雌激素水平，并分析了血清PCSK9水平与雌激素水平的相关性。此外，还进行了细胞培养研究，以检测生理和非生理浓度的雌激素是否调节肝细胞PCSK9的表达。血清PCSK9浓度随增龄而显著升高。老年组血清PCSK9水平高于中年组和青年组(60.29±28.47vs71.38+/-34.22vs83.81+/-33.50 ng/ml)。血清PCSK9水平与年龄、BMI、血清总胆固醇、低密度脂蛋白呈正相关(P<；0.01)，与雌激素水平无相关性。727例妇女血清PCSK9水平在雌二醇(E_2)水平上下两组间无显著差异。30名健康育龄妇女月经期、排卵期、黄体期PCSK9水平均无显著差异。细胞培养研究表明，生理浓度的17β-雌二醇对人肝细胞PCSK9的表达无明显影响。绝经后妇女血清PCSK9水平高于绝经前妇女。然而，绝经后和绝经前妇女血清PCSK9水平的差异似乎与雌激素状态无关，生理浓度的雌激素不影响人类肝细胞PCSK9的表达。(C)2015 Elsevier Inc.保留所有权利。
Objective. We previously reported that serum PCSK9 levels are higher in postmenopausal women than in premenopausal women in a Han Chinese population. Whether this difference is related to estrogen has not been well-characterized. This study aims to examine if the alteration in estrogen level is responsible for the changes of serum PCSK9 concentration.Materials/Methods. A sandwich ELISA assay was used to measure serum PCSK9 levels in 727 healthy women aged from 26 to 85 years old. Anthropometric and biochemical examination of parameters such as estrogen and serum lipids was also performed for these individuals. Next, we measured serum PCSK9 and estrogen levels of 30 healthy fertile women (24-26 years old) in their menstrual cycles and analyzed the correlation between serum PCSK9 level and estrogen concentration. Moreover, cell culture studies were carried out to examine if estrogen at physiological and non-physiological concentrations regulates hepatocyte PCSK9 expression.Results. Serum PCSK9 concentrations were significantly increased with aging. Aged group had higher serum PCSK9 levels than the middle aged group and the young group (60.29 +/- 28.47 vs 71.38 +/- 34.22 vs 83.81 +/- 33.50 ng/ml). Serum PCSK9 levels were positively correlated with age, BMI, serum total cholesterol and LDL-cholesterol (P < 0.01), but not correlated with estrogen levels. There was no significantly difference of PCSK9 levels between the lower and the upper estradiol (E2) tertiles in the 727 women. There was either no significant difference in PCSK9 levels during the menstrual, ovulatory, luteal phases in the 30 healthy fertile women. Cell culture studies showed that 17 beta-estradiol at physiological concentrations did not significantly alter PCSK9 expression in human hepatocytes.Conclusion. The serum PCSK9 levels were higher in postmenopausal women than those in pre-menopausal women. However, the difference in serum PCSK9 levels between postmenopausal and premenopausal woman appeared to be independent of estrogen status, and estrogen at physiological concentrations does not affect human hepatocyte PCSK9 expression. (C) 2015 Elsevier Inc. All rights reserved.