Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing, People's Republic of China.
Comp Biochem Physiol C Toxicol Pharmacol. 2012 Jun;156(1):17-23. doi: 10.1016/j.cbpc.2012.03.001. Epub 2012 Mar 9.
In the aquatic environment, both the estrogen receptor (ER) and aryl hydrocarbon receptor (AhR) responses are established biomarkers for assessing exposure to pollutants. These receptor responses can also be affected by the presence of other classes of pollutants and may result in misinterpretation of existing pollution. In this study, we investigated the interaction between ER-vitellogenin (VTG) and AhR-cytochrome P450 1A (CYP1A) signaling pathways in goldfish (Carassius auratus) after 10 days exposure to pollutants. 17β-Estradiol (E(2)) and benzo[a]pyrene (BaP) were selected as the ER and AhR agonists, respectively. The messenger RNA (mRNA) expression of ER-VTG and AhR-CYP1A in liver was determined using quantitative real-time polymerase chain reaction (QRT-PCR). VTG, endogenous E(2) and 7-ethoxyresorufin-O-deethylase (EROD) were also studied. Exposure to E(2) and BaP alone significantly induced the gene expression of ERα-VTG and AhR2-CYP1A, respectively. Moreover, the obvious expression of related proteins was also observed. However, these inductions were significantly reduced after combined exposure to E(2) and lower concentrations of BaP (20 and 50 μg/L), indicative of a reciprocal inhibiting ER-AhR interaction. However, high concentrations (100 μg/L) of BaP did not affect the E(2)-induced gene expression. Changes in VTG protein were in accordance with the expression of VTG mRNA, and more VTG protein was observed in liver than in serum. The induced endogenous E(2) levels were suppressed by the presence of BaP. While the gene expression of CYP1A showed a concentration-dependent increase, EROD induction exhibited a bell-shaped concentration-response curve. Taken together, these results demonstrate a reciprocal inhibiting mode of ER-AhR interactions and may lead to a possible underestimation of actual exposure.
在水生环境中，雌激素受体 (ER) 和芳香烃受体 (AhR) 反应都是评估污染物暴露的既定生物标志物。这些受体反应也可能受到其他类别的污染物的影响，并可能导致对现有污染的错误解释。在这项研究中，我们在金鱼（Carassius auratus）暴露于污染物 10 天后，研究了 ER-卵黄蛋白原 (VTG) 和 AhR-细胞色素 P450 1A (CYP1A) 信号通路之间的相互作用。17β-雌二醇 (E(2)) 和苯并[a]芘 (BaP) 分别被选为 ER 和 AhR 激动剂。使用实时定量聚合酶链反应 (QRT-PCR) 测定肝脏中 ER-VTG 和 AhR-CYP1A 的信使 RNA (mRNA) 表达。还研究了 VTG、内源性 E(2) 和 7-乙氧基荧蒽-O-脱乙基酶 (EROD)。单独暴露于 E(2) 和 BaP 均显著诱导 ERα-VTG 和 AhR2-CYP1A 的基因表达。此外，还观察到相关蛋白的明显表达。然而，在联合暴露于 E(2) 和较低浓度 BaP（20 和 50 μg/L）时，这些诱导作用明显降低，表明 ER-AhR 相互作用呈相互抑制状态。然而，高浓度（100 μg/L）的 BaP 并不影响 E(2) 诱导的基因表达。VTG 蛋白的变化与 VTG mRNA 的表达一致，并且在肝脏中观察到的 VTG 蛋白多于在血清中。BaP 的存在抑制了诱导的内源性 E(2) 水平。虽然 CYP1A 的基因表达表现出浓度依赖性增加，但 EROD 诱导呈钟形浓度反应曲线。综上所述，这些结果表明 ER-AhR 相互作用呈相互抑制模式，可能导致对实际暴露的低估。
