Effects of 17α-ethynylestradiol on hormonal responses and xenobiotic biotransformation system of Atlantic salmon (Salmo salar)
Effects of 17α-ethynylestradiol on hormonal responses and xenobiotic biotransformation system of Atlantic salmon (Salmo salar)
复制标题
DOI：
10.1016/j.aquatox.2007.08.004
复制
发表时间：
2007-11-30
影响因子：
4.5
通讯作者：
Arukwe, Augustine
中科院分区：
文献类型：
--
作者：
Mortensen, Anne S.;Arukwe, Augustine
药物是水环境中普遍存在的污染物，它们对鱼类等非目标物种的潜在影响直到最近才成为系统调查的对象。本研究采用定量(实时)聚合酶链式反应(QPCR)、VTG-EL ISA和7-乙氧基间苯二酚O-脱乙基酶(EROD)催化活性研究了人工合成药物内分泌干扰物乙炔雌二醇(E_2)对鲑鱼幼鱼肝脏I、II相生物转化和激素途径的影响。乙炔雌二醇的剂量为5或50 ng/L。我们的数据显示，EE2对雌激素受体亚型(ERα、ERβ)和雄激素受体-β(ARβ)产生时间和浓度特异性的调制。EE2在暴露后第3天产生浓度特异性的卵黄蛋白原(VTG)和辐射带蛋白(Zr-Protein)。7d时，与二甲基亚砜对照组相比，给予5 ng EE2/L组大鼠血浆VTG、VTG和Zr蛋白的表达显著降低。在异种生物转化途径中，给予5 ng EE2/L组第3天芳香烃受体-α(AhRα)显著增加，第7天相同浓度的AhRβ显著降低。而细胞色素P3A无明显变化，而细胞色素P1A1、AhR核转位蛋白(ARNT)和AhR阻遏因子(AHRR)的基因表达呈明显的EE2浓度和时间依赖性下降。在染毒后第3天和第7天，50 ng雌二醇/L组大鼠尿苷二磷酸葡萄糖醛酸基转移酶(UGT)和谷胱甘肽-S转移酶样(GSTpi-like)基因的表达均明显降低。EE2对细胞色素P1A1基因表达的影响与对EROD和AHRR基因表达的影响是平行的，提示EE2对细胞解毒机制具有直接调控作用。有趣的是，载体载体DMSO在暴露后第7天与空白对照(即不含DMSO的对照组)相比，产生了显著的雌激素样反应(ERα、VTG和Zr蛋白)，并具有明显的时间依赖性。DMSO的影响完全强调了在暴露后第7天观察到的EE2效应。总体而言，这些发现支持先前关于EE2对内分泌的影响以及对肝脏生物转化系统的影响的报道。鉴于本文提供的数据和我们最近的研究，应重新评估在内分泌毒理学实验研究中使用DMSO作为载体的情况。(C)2007 Elsevier B.V.保留所有权利。
Pharmaceuticals are ubiquitous pollutants in the aquatic environment where their potential effects on non-target species like fish has only recently become subject of systematic investigations. In the present study, experiments were undertaken to examine the effects of a synthetic pharmaceutical endocrine disruptor, ethynylestradiol (EE2), given in water at 5 or 50 ng/L and sampled at days 0 (control), 3 and 7 after exposure, on hepatic phase I and II biotransformation and hormonal pathways of juvenile salmon using quantitative (real-time) polymerase chain reaction (qPCR), Vtg ELISA and 7-ethoxyresorufin O-deethylase (EROD) catalytic activity. Our data show that EE2 produced time- and concentration-specific modulation of estrogen receptor isoforms (ER alpha, ER beta) and androgen receptor-beta (AR beta). EE2 produced a concentration-specific induction of vitellogenin (Vtg) and zona radiata protein (Zr-protein) at day 3 after exposure. At day 7, Vtg and Zr-protein mRNA (and plasma Vtg protein) expression were significantly decreased in the group given 5 ng EE2/L, compared to dimethyl sulfoxide (DMSO) control group. In the xenobiotic biotransformation pathway, EE2 produced a significant increase of aryl hydrocarbon receptor-a (AhR alpha) at day 3 in the group given 5 ng EE2/L and AhR beta was decreased at the same concentration at day 7. While CYP3A was not significantly affected by EE2 exposure, the CYP1 A1, AhR nuclear translocator (Arnt) and AhR repressor (AhRR) mRNA showed an apparent EE2 concentration and time-dependent decrease. The expression of uridine diphosphoglucuronosyl transferase (UGT) and glutathione S-transferase class pi-like (GSTpi-like) mRNA were decreased after exposure to 50 ng EE2/L at both day 3 and 7 after exposure. The effect of EE2 on the CYP1 A 1 gene expressions paralleled effect on EROD and AhRR mRNA, suggesting a direct role of EE2 in controlling cellular detoxification machinery. Interestingly, the carrier vehicle, DMSO produced significant time-dependent induction of estrogenic (ER alpha, Vtg and Zr-protein) responses, compared with blank (i.e. without DMSO) controls at day 7 post-exposure. The effect of DMSO totally underscored the observed EE2 effect at day 7 after exposure. In general, these findings support previous reports on the endocrine effects of EE2, in addition to effects on hepatic biotransformation system. In view of the data presented here and our recent studies, the use of DMSO as carrier vehicle in endocrine toxicological experimental studies should be re-evaluated. (c) 2007 Elsevier B.V. All rights reserved.