Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, 1 Xikang Road, Nanjing 210098, China.
Aquat Toxicol. 2013 May 15;132-133:19-25. doi: 10.1016/j.aquatox.2013.01.015. Epub 2013 Feb 8.
An understanding of the effects of toxic mixtures of endocrine disrupting chemicals (EDCs) on aquatic organisms is challenging as these organisms are exposed to multiple classes of contaminants in their natural habitat. The aim of the present study was to evaluate the interactions of two classes of EDCs, 17β-estradiol (E2) and ketoconazole (KTC), on endocrine function in male goldfish (Carassius auratus), including vitellogenesis, metabolic capability and serum steroid synthesis. Changes in vitellogenin (VTG) concentration, liver 7-ethoxyresorufin-O-deethylase (EROD) activity and circulating serum E2 level were examined. The expression of related genes was also determined using quantitative real-time polymerase chain reaction. Exposure to E2 caused a significant increase in VTG concentrations which corresponded with the gene expression of VTG and estrogen receptor (ER) in males, which were further elevated after combined exposure to E2 and KTC, indicative of a synergetic relationship. Exposure to E2 also resulted in a distinct increase in serum steroid biosynthesis and associated cytochrome P450 (CYP) aromatase expression after 10 days. However, these changes were inhibited by the presence of KTC, which acted as a steroidogenic inhibitor in fish. Moreover, KTC significantly decreased liver EROD activity and increased the related gene expression of CYP1A. However, these KTC-mediated metabolic reactions in goldfish were up-regulated following exposure to KTC in combination with E2. These findings reveal complex interactions on endocrine functions in male goldfish when exposed to multiple contaminations and may provide a better understanding of the effects of toxic mixtures.
了解内分泌干扰化学物质（EDCs）的有毒混合物对水生生物的影响具有挑战性，因为这些生物体在其自然栖息地中会接触到多种类别的污染物。本研究旨在评估两类 EDCs，即 17β-雌二醇（E2）和酮康唑（KTC），对雄性金鱼（Carassius auratus）内分泌功能的相互作用，包括卵黄蛋白原生成、代谢能力和血清类固醇合成。检测了卵黄蛋白原（VTG）浓度、肝脏 7-乙氧基resorufin-O-去乙基酶（EROD）活性和循环血清 E2 水平的变化。还使用定量实时聚合酶链反应确定了相关基因的表达。暴露于 E2 导致 VTG 浓度显著增加，这与雄性鱼中 VTG 和雌激素受体（ER）的基因表达相对应，而在 E2 和 KTC 联合暴露后进一步升高，表明存在协同关系。暴露于 E2 还导致血清类固醇生物合成及其相关细胞色素 P450（CYP）芳香酶表达在 10 天后明显增加。然而，这些变化被 KTC 抑制，KTC 在鱼类中作为一种甾体生成抑制剂发挥作用。此外，KTC 显著降低了肝脏 EROD 活性并增加了 CYP1A 的相关基因表达。然而，这些 KTC 介导的金鱼代谢反应在与 E2 联合暴露于 KTC 后被上调。这些发现揭示了雄性金鱼暴露于多种污染物时对内分泌功能的复杂相互作用，并可能更好地了解有毒混合物的影响。
