Polychlorinated biphenyl exposure and CYP19 gene regulation in testicular and adrenocortical cell lines
Polychlorinated biphenyl exposure and CYP19 gene regulation in testicular and adrenocortical cell lines
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DOI：
10.1016/j.tiv.2007.04.002
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发表时间：
2007-09-01
影响因子：
3.2
通讯作者：
Li, Lih-Ann
中科院分区：
文献类型：
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作者：
Li, Lih-Ann
接触多氯联苯 (PCB) 会扰乱许多雌激素介导的生化过程。 PCB 可能通过改变芳香酶基因 CYP19 的表达而导致这些异常。这项研究表明，高浓度的 PCB126 增加了小鼠睾丸 Leydig 1-10 细胞和人肾上腺皮质 H295R 细胞中基础 CYP19 mRNA 的丰度。用绒毛膜促性腺激素或 8-Br-cAMP 刺激细胞掩盖了 PCB126 的雌激素作用。 PCB126 是核受体 AhR 的强大配体。通过抑制剂拮抗 H295R 的 AhR 活性，消除了 PCB126 引发的 CYP19 诱导。然而，PCB126 以缓慢渐进的方式升高基础 CYP19 表达和芳香酶活性，这与经典 AhR 靶基因 CYP1A1 的急剧诱导相反。将 H295R 暴露于具有不同 AhR 激活能力的 PCB 也会以不同的模式改变 CYP19 和 CYP1A1 的表达，尽管 CYP19 mRNA 水平与同源物的 AhR 激活能力一致。与 PCB126 相比，PCB39 不能激活 AhR 并且对 CYP1A1 缺乏影响，但显着降低 CYP19 mRNA 表达。 AhR 显然在 CYP19 基因调控中发挥着重要作用，但它在肾上腺皮质细胞中对 CYP19 的调控可能与 CYP1A1 不同。无论作用机制如何，PCB 暴露都会增加 CYP19 失调的风险。 (C) 2007 Elsevier Ltd. 保留所有权利。
Exposure to polychlorinated biphenyls (PCBs) disturbs many estrogen-mediated biochemical processes. PCBs may cause these abnormalities by altering expression of the aromatase gene CYP19. This study demonstrated that high concentrations of PCB126 increased basal CYP19 mRNA abundance in mouse testicular Leydig 1-10 cells and human adrenocortical H295R cells. Stimulating the cells with chorionic gonadotropin or 8-Br-cAMP concealed the estrogenic effect of PCB126. PCB126 is a powerful ligand for nuclear receptor AhR. Antagonizing the AhR activity of H295R by an inhibitor abolished PCB126-elicited CYP19 induction. However, PCB126 elevated basal CYP19 expression and aromatase activity in a slow progressive manner contrary to the sharp induction of the classic AhR target gene CYP1A1. Exposure of H295R to PCBs with different AhR activation abilities also varied CYP19 and CYP1A1 expression in dissimilar patterns, although the CYP19 mRNA levels were in line with the AhR activation abilities of the congeners. In contrast to PCB126, PCB39, which could not activate AhR and lacked effect on CYP1A1, significantly reduced CYP19 mRNA expression. AhR apparently played an important role in CYP19 gene regulation, but it might regulate CYP19 differently from CYP1A1 in the adrenocortical cells. Regardless of the action mechanism, PCB exposure increases risk for CYP19 dysregulation. (C) 2007 Elsevier Ltd. All rights reserved.