Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors.
Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors.
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DOI：
10.1016/j.taap.2014.07.020
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发表时间：
2014-10-01
影响因子：
3.8
通讯作者：
Balaguer P
中科院分区：
文献类型：
--
作者：
Pinto C;Grimaldi M;Boulahtouf A;Pakdel F;Brion F;Aït-Aïssa S;Cavaillès V;Bourguet W;Gustafsson JA;Bondesson M;Balaguer P
斑马鱼Danio rerio越来越多地被用作研究药物和环境雌激素影响的动物模型。由于这些雌激素大多只在人类雌激素受体(ER)上进行过测试，因此有必要测量它们对斑马鱼ER的影响。在人类中存在两个不同的核ER(Herα和Herβ)，而斑马鱼基因组编码三个ER，ZFERα和两个ZFERβS(ZFERβ1和ZFERβ2)。在本研究中，我们建立了稳定表达这三个zfERs的HeLa报告细胞系。我们首次报道了雌激素在28℃比37℃更有效地激活zfERs，从而反映了斑马鱼在野生动物中的生理温度。然后，我们显示了激动剂和拮抗剂雌激素调节三种ZfER同种类型激活的能力与她的显著不同。与ZfERβα选择性激动剂相比，环境化合物(双酚A、烷基酚、霉菌雌激素)对ZfERβ有更强的活性。在她的α选择性合成激动剂中，PPT不能激活ZfERα，而16α-α是最有选择性的化合物。总之，这些结果证实了她所有的配体都以相似的方式控制zfERs的转录活性，尽管在不同亚型之间观察到显著的选择性差异。因此，我们确定的zfER亚型选择性配体为剖析不同zfER的生理作用提供了新的有价值的工具。最后，我们的工作还指出，在将斑马鱼作为人类生理病理学模型所获得的结果转置时必须小心。
Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28 °C as compared to 37 °C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology.
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影响因子：
2.7
作者：
Notch, Emily G.;Mayer, Gregory D.
通讯作者：
Mayer, Gregory D.
DOI：
10.1101/sqb.1986.051.01.088
发表时间：
1986-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
GREEN, S;KUMAR, V;CHAMBON, P
通讯作者：
CHAMBON, P
影响因子：
15
作者：
Manas, ES;Unwalla, RJ;Alvarez, JC
通讯作者：
Alvarez, JC
DOI：
10.1016/s0960-0760(02)00159-0
发表时间：
2002-10-01
影响因子：
4.1
作者：
Matthews, JB;Fertuck, KC;Zacharewski, TR
通讯作者：
Zacharewski, TR
影响因子：
9.8
作者：
Balaguer, P;François, F;Casellas, C
通讯作者：
Casellas, C