Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the expression of cytochrome P450 1A1, the aryl hydrocarbon receptor, and the aryl hydrocarbon receptor nuclear translocator in rat brain and pituitary
Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the expression of cytochrome P450 1A1, the aryl hydrocarbon receptor, and the aryl hydrocarbon receptor nuclear translocator in rat brain and pituitary
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DOI：
10.1006/taap.2000.9064
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发表时间：
2000-12-01
影响因子：
3.8
通讯作者：
Ceccatelli, S
中科院分区：
文献类型：
--
作者：
Huang, P;Rannug, A;Ceccatelli, S
2,3,7,8-四氯二苯并-对二恶英（TCDD）及其相关物质是普遍存在的环境污染物，可引起多种病理改变，最严重的是进行性厌食症和体重减轻。这些特征表明可能涉及神经系统和神经内分泌相关器官，包括脑下垂体。然而，到目前为止，几乎没有证据表明TCDD对这些地区产生了直接影响。在本研究中，雄性Sprague-Dawley大鼠单次口服TCDD(10杯/kg)，并在治疗后1、3、28天实施安乐死。采用半定量RT-PCR和Western blotting分析细胞色素P450 1A1 （CYP1A1）、芳烃受体（AHR）和芳烃受体核转运子（ARNT）在不同脑区和垂体中的表达。垂体组织中CYP1A1 mRNA和蛋白的相对水平显著升高。在所有被检查的大脑区域，包括嗅球、纹状体-尾状体、下丘脑、海马、皮层、小脑和黑质，也检测到CYP1A1 mRNA的显著增加。表达的增加具有时间依赖性，在TCDD治疗后1天达到最高水平。在相同区域检测到AHR和ARNT mRNA，但与CYP1A1相比，AHR和ARNT mRNA表达的变化仅限于28天时间点。目前的结果为中枢神经系统和垂体中存在CYP1A1、AHR和ARNT提供了证据，表明TCDD可能对这些区域产生直接影响。(C) 2000年学术出版社。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related substances are ubiquitous environmental pollutants causing a wide variety of pathological alterations, with the most severe being progressive anorexia and body weight loss. These features suggest a possible involvement of the nervous system and neuroendocrine-related organs including the pituitary gland. However, so far there is little evidence for direct effects of TCDD on these areas. In the present study, male Sprague-Dawley rats were treated with a single oral dose of TCDD (10 mug/kg) and euthanized 1, 3, err 28 days after treatment. The expression of cytochrome P450 1A1 (CYP1A1), the aryl hydrocarbon receptor (AHR), and the aryl hydrocarbon receptor nuclear translocator (ARNT) were analyzed in different brain regions and pituitaries using semiquantitative RT-PCR and Western blotting. Relative levels of CYP1A1 mRNA and protein were dramatically increased in the pituitary. A significant increase in CYP1A1 mRNA was also detected in all the brain regions examined including olfactory bulb, striatum-caudate, hypothalamus, hippocampus, cortex, cerebellum, and substantia nigra. The increase in the expression was time-dependent with the highest level observed 1 day after TCDD treatment. The AHR and ARNT mRNAs were detected in the same areas but in contrast to CYP1A1 the changes in AHR and ARNT mRNA expression were limited to the 28-day time point. The present results provide evidence for the presence of CYP1A1, AHR, and ARNT in the central nervous system and in the pituitary, suggesting that TCDD may exert a direct effect on these regions. (C) 2000 Academic Press.