Tissue-specific estrogenic and non-estrogenic effects of a xenoestrogen, nonylphenol.
Tissue-specific estrogenic and non-estrogenic effects of a xenoestrogen, nonylphenol.
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DOI：
10.1677/jme.0.0330243
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发表时间：
2004-08
影响因子：
3.5
通讯作者：
Hajime Watanabe;A. Suzuki;M. Goto;D. Lubahn;H. Handa;T. Iguchi
中科院分区：
文献类型：
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作者：
Hajime Watanabe;A. Suzuki;M. Goto;D. Lubahn;H. Handa;T. Iguchi
烷基酚扰乱内分泌系统，被认为具有弱雌激素活性。尽管已知壬基酚与雌激素受体的结合较弱，但尚不清楚壬基酚的所有报道效应是否均归因于其雌激素受体结合活性。为了研究烷基酚是否具有与天然激素雌二醇相似的作用，我们使用小鼠模型来研究壬基酚对基因表达的影响，并将其与雌二醇进行比较。DNA微阵列分析显示，在子宫中，大部分被高剂量（50 mg/kg）烷基酚激活的基因也被雌二醇激活。在较低剂量下，壬基酚（0.5 mg/kg和5 mg/kg）对雌二醇激活的基因几乎没有影响。因此，我们得出结论，高剂量（50 mg/kg）壬基酚的作用与子宫组织中的雌二醇非常相似。此外，由于通过基因表达水平评价雌激素活性与子宫增重试验相当，因此表明基因表达谱分析可以预测化学品的雌激素活性。与壬基酚和雌二醇在子宫中观察到的类似作用相反，在肝脏中，壬基酚比雌二醇对基因表达的影响更明显。这表明，在肝脏中，壬基酚可以激活另一组与雌激素反应基因不同的基因。这些结果表明，壬基酚具有非常相似的影响，雌二醇在子宫中的基因表达，但不是在肝脏组织，这表明组织特异性的影响，应被考虑，以阐明不同的影响烷基酚。
Alkylphenols perturb the endocrine system and are considered to have weak estrogenic activities. Although it is known that nonylphenol can bind weakly to the estrogen receptor, it is unclear whether all reported effects of nonylphenol are attributable to its estrogen receptor-binding activity. In order to examine whether alkylphenols have similar effects to the natural hormone, estradiol, we used a mouse model to examine the effects of nonylphenol on gene expression and compared it with estradiol. DNA microarray analysis revealed that, in the uterus, most of the genes activated by this alkylphenol at a high dose (50 mg/kg) were also activated by estradiol. At lower doses, nonylphenol (0.5 mg/kg and 5 mg/kg) had little effect on the genes that were activated by estradiol. Thus, we concluded that the effects of nonylphenol at a high dose (50 mg/kg) were very similar to estradiol in uterine tissue. Moreover, since evaluation of estrogenic activity by gene expression levels was comparable with the uterotrophic assay, it indicated that analysis of gene expression profiles can predict the estrogenic activities of chemicals. In contrast to the similar effects of nonylphenol and estradiol observed in the uterus, in the liver, gene expression was more markedly affected by nonylphenol than by estradiol. This indicated that, in the liver, nonylphenol could activate another set of genes that are distinct from estrogen-responsive genes. These results indicated that nonylphenol has very similar effects to estradiol on gene expression in uterine but not in liver tissue, indicating that tissue-specific effects should be considered in order to elucidate the distinct effects of alkylphenols.