Walsh Deirdre E, Dockery Peter, Doolan Christina M
Department of Physiology, Biosciences Institute, University College Cork, Cork, Ireland.
Mol Cell Endocrinol. 2005 Jan 31;230(1-2):23-30. doi: 10.1016/j.mce.2004.11.006.
The aim of this study was to identify and characterize an alternative pathway through which environmental estrogenic compounds may mediate their intracellular effects. Three human breast cancer cell lines were employed including MCF-7 cells, which express both ERalpha and ERbeta; MDA-MB-231 cells, which express ERbeta but not ERalpha; and SKBR-3 cells, which express neither ERalpha nor ERbeta. The effect of environmental estrogenic compounds on intracellular calcium ion concentration (Ca(2+)) was measured and compared to that of 17beta-estradiol (E2). A rapid and maintained increase in Ca(2+) was observed following the application of nanomolar concentrations of environmental estrogens and E2 regardless of the expression of ERalpha and ERbeta. Removal of extracellular Ca(2+) completely abolished the steroid-induced Ca(2+) increase. Pre-treatment of cells with the estrogen receptor (ER) antagonist ICI 182,780 had no effect on either basal Ca(2+) or the steroid-triggered Ca(2+) response. In summary, we have demonstrated ER independent rapid non-genomic effects of environmental estrogenic compounds, at nanomolar concentrations, on Ca(2+). The results of this study demonstrate an alternative pathway to explain potent intracellular effects of endocrine disrupting chemicals.
本研究的目的是识别和表征环境雌激素化合物可能介导其细胞内效应的另一种途径。使用了三种人乳腺癌细胞系，包括同时表达雌激素受体α（ERα）和雌激素受体β（ERβ）的MCF-7细胞；表达ERβ但不表达ERα的MDA-MB-231细胞；以及既不表达ERα也不表达ERβ的SKBR-3细胞。测量了环境雌激素化合物对细胞内钙离子浓度（Ca(2+)）的影响，并与17β-雌二醇（E2）的影响进行了比较。无论ERα和ERβ的表达情况如何，在应用纳摩尔浓度的环境雌激素和E2后，均观察到Ca(2+)迅速且持续增加。去除细胞外Ca(2+)完全消除了类固醇诱导的Ca(2+)增加。用雌激素受体（ER）拮抗剂ICI 182,780预处理细胞对基础Ca(2+)或类固醇触发的Ca(2+)反应均无影响。总之，我们已经证明了环境雌激素化合物在纳摩尔浓度下对Ca(2+)具有不依赖ER的快速非基因组效应。本研究结果证明了一种解释内分泌干扰化学物质强大细胞内效应的替代途径。
