Three Structurally Different Polychlorinated Biphenyl Congeners (Pcb 118, 153, and 126) Affect Hormone Production and Gene Expression in the Human H295R In Vitro Model
Three Structurally Different Polychlorinated Biphenyl Congeners (Pcb 118, 153, and 126) Affect Hormone Production and Gene Expression in the Human H295R In Vitro Model
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DOI：
10.1080/15287394.2010.484338
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发表时间：
2010-01-01
影响因子：
2.6
通讯作者：
Verhaegen, Steven
中科院分区：
文献类型：
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作者：
Kraugerud, Marianne;Zimmer, Karin E.;Verhaegen, Steven
多氯联苯(PCBs)是一种普遍存在的环境污染物，与包括内分泌干扰在内的不良健康影响有关。本研究比较了单邻位取代的多氯联苯118和二邻位取代的多氯联苯153与非邻位取代的多氯联苯126对类固醇激素产生的可能影响以及对参与类固醇合成的10个编码蛋白的表达的影响。以H295R人腺癌细胞系为体外模型。将细胞暴露于溶剂对照(二甲基亚砜，DMSO)或三种测试化合物之一的6种不同浓度(从40 PM到4M)中48h。这三种同系物都显著增加了雌二醇-17的产生。与PCB126相似，PCB118以浓度依赖的方式产生孕酮和皮质醇的上升。对多氯联苯153的反应是，睾丸激素显著降低，但对多氯联苯118或多氯联苯126没有影响。所有三种同系物都在测试的最高浓度下升高了醛固酮。3种同系物作用后，细胞内细胞色素P11B2基因表达水平均显著升高。此外，PCB126在测试的最高浓度下上调了CYP19、3-HSD2、STAR和HMGR的mRNA水平，并在40 nM时下调了CYP21的表达。总之，所有三种多氯联苯同系物都能够以浓度依赖的方式调节H295R中类固醇的合成，因此多氯联苯118暴露后的激素谱类似于多氯联苯126。就基因表达谱的变化而言，接触多氯联苯126的影响最大。
Polychlorinated biphenyls (PCB) are ubiquitous environmental pollutants that have been linked to adverse health effects including endocrine disruption. This study compared the mono-ortho-substituted PCB 118 and di-ortho-substituted PCB 153 with the non-ortho-substituted PCB 126, for possible effects on steroid hormone production and on the expression of 10 genes encoding proteins involved in steroidogenesis. The H295R human adenocarcinoma cell line was used as an in vitro model. Cells were exposed for 48 h to solvent control (dimethyl sulfoxide, DMSO) or 6 different concentrations ranging from 40 pM to 4 M of one of the three test compounds. All three congeners significantly increased the production of estradiol-17. PCB 118 produced a rise in progesterone and cortisol in a concentration-dependent manner, similar to PCB 126. Testosterone was significantly reduced in response to PCB 153 but not PCB 118 or PCB 126. All three congeners elevated aldosterone at the highest concentration tested. A significant increase was observed in CYP11B2 mRNA levels in cells exposed to the three congeners. In addition, PCB 126 upregulated CYP19, 3-HSD2, StAR, and HMGR mRNA levels at the highest concentration tested, and downregulated CYP21 at 40 nM. In conclusion, all three PCB congeners are capable of modulating steroidogenesis in H295R in a concentration-dependent manner, whereby the hormone profile following PCB 118 exposure resembles that of PCB 126. Where changes in gene expression profile are concerned, exposure to PCB 126 showed the greatest effects.