In vivo profiling of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced estrogenic/anti-estrogenic effects in female estrogen-responsive reporter transgenic mice.
In vivo profiling of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced estrogenic/anti-estrogenic effects in female estrogen-responsive reporter transgenic mice.
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DOI：
10.1016/j.jhazmat.2019.121526
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发表时间：
2019-10
影响因子：
13.6
通讯作者：
Ichiro Yoshida;K. Ishida;Hiroshi Yoshikawa;S. Kitamura;Youhei Hiromori;Yasushi Nishioka;A. Ido
中科院分区：
文献类型：
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作者：
Ichiro Yoshida;K. Ishida;Hiroshi Yoshikawa;S. Kitamura;Youhei Hiromori;Yasushi Nishioka;A. Ido
2,3,7,8-四氯二苯并-对二恶英（TCDD），通常简称为“二恶英”，是一种持久性环境污染物。由于其高环境持久性和生物累积性，人类和动物经常接触TCDD。因此，对人类和动物的有害影响是一个主要问题。尽管研究已经阐明了 TCDD 的不良雌激素和抗雌激素作用，但尚不清楚 TCDD 在体内哪些组织中发挥这些作用。为了研究 TCDD 在各种组织中与雌激素相关的作用，我们培育了一种改良的雌激素响应报告基因转基因小鼠，其中荧光素酶基因 luc2 响应雌激素信号而表达。使用这些小鼠，我们阐明了 TCDD 抑制同一个体肝脏和肾脏中的雌激素信号，但增强垂体中的雌激素信号。在肝脏、肾脏和垂体中检测到芳烃受体、芳烃受体核转位子和雌激素受体α mRNA的表达，表明TCDD对这些器官中雌激素信号传导的影响与这些受体的表达模式无关。因此，我们的结果表明 TCDD 在同一个体内发挥雌激素和抗雌激素组织特异性作用。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), commonly referred to simply as “dioxin”, is a persistent environmental pollutant. Because of its high environmental persistence and biological accumulation, humans and animals are often exposed to TCDD. Therefore, the harmful effects on humans and animals is a major concern. Although studies have elucidated the adverse estrogenic and anti-estrogenic effects of TCDD, it is unclear in which tissues TCDD exerts these effectsin vivo. To investigate the estrogen-related effects of TCDD in various tissues, we generated an improved estrogen-responsive reporter transgenic mouse in which the luciferase geneluc2is expressed in response to estrogenic signals. Using these mice, we clarified that TCDD inhibits estrogenic signaling in liver and kidney but enhances estrogenic signaling in the pituitary gland in the same individual. Expression of aryl hydrocarbon receptor, aryl hydrocarbon receptor nuclear translocator, and estrogen receptor alpha mRNA was detected in liver, kidney, and pituitary gland, suggesting that the effects of TCDD on estrogenic signaling in these organs is independent of the expression pattern of these receptors. Thus, our results indicate that TCDD exerts both estrogenic and anti-estrogenic tissue-specific effects within the same individual.