Wober Jannette, Weisswange Ina, Vollmer Günter
Molecular Cell Physiology and Endocrinology, Institute of Zoology, Dresden University of Technology, Mommsenstr. 13, 01062 Dresden, Germany.
J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):227-33. doi: 10.1016/s0960-0760(02)00252-2.
Xenoestrogens, phytoestrogens and synthetic estrogens, are able to bind to estrogen receptors, and to mimic estrogenic activities in a cell and tissue specific manner. For the characterization of environmental estrogens mainly mammary derived and yeast based models have been used. The aim of this study was therefore to assess selected natural and synthetic compounds in an endometrial derived model. We measured the relative estrogenic potency of phytoestrogens (genistein, daidzein, coumestrol, some naringenins), synthetic estrogens (bisphenol A, octylphenol, nonylphenol, o,p'-DDT), mycoestrogen (zearalanone) as well as extracts of Cimicifuga racemosa on alkaline phosphatase (AlkP) activity in the endometrial derived adenocarcinoma cell line Ishikawa. We used a modified multiwell plate in vitro bioassay based on the estrogen-specific and dose-dependent enhancement of AlkP activity in this cell line. Estradiol, which induced AlkP at levels as low as 10(-8)M, was used as positive control. Most of the compounds studied showed a clear dose-dependent estrogenic effect. Compared to the vehicle control (ethanol) all phyto- and mycoestrogens, stimulated the AlkP activity 2-4-fold at a concentration of 10(-6)M. The synthetic chemicals bisphenol A and nonylphenol showed an effect at 10(-6)M, octylphenol at 10(-5)M. Effects of o,p'-DTT could not be measured. ICI 182,780, a pure estrogen receptor antagonist, significantly inhibited these effects. The latter result demonstrated the estrogen receptor dependency of this process. In summary, most of the phytoestrogens and industrial chemicals tested, behaved as estrogen receptor agonists in terms of the stimulation of AlkP activity.
异雌激素、植物雌激素和合成雌激素能够与雌激素受体结合，并以细胞和组织特异性方式模拟雌激素活性。为了表征环境雌激素，主要使用了源自乳腺和基于酵母的模型。因此，本研究的目的是在源自子宫内膜的模型中评估选定的天然和合成化合物。我们测量了植物雌激素（染料木黄酮、大豆苷元、香豆雌酚、一些柚皮苷）、合成雌激素（双酚A、辛基酚、壬基酚、o,p'-滴滴涕）、霉菌雌激素（玉米赤霉烯酮）以及升麻提取物对源自子宫内膜的腺癌细胞系 Ishikawa 中碱性磷酸酶（AlkP）活性的相对雌激素效力。我们使用了一种基于该细胞系中 AlkP 活性的雌激素特异性和剂量依赖性增强的改良多孔板体外生物测定法。雌二醇在低至 10(-8)M 的水平诱导 AlkP，用作阳性对照。大多数研究的化合物显示出明显的剂量依赖性雌激素效应。与溶剂对照（乙醇）相比，所有植物雌激素和霉菌雌激素在 10(-6)M 的浓度下刺激 AlkP 活性 2 - 4 倍。合成化学品双酚 A 和壬基酚在 10(-6)M 时显示出效应，辛基酚在 10(-5)M 时显示出效应。无法测量 o,p'-DTT 的效应。ICI 182,780，一种纯雌激素受体拮抗剂，显著抑制了这些效应。后一结果证明了该过程对雌激素受体的依赖性。总之，就刺激 AlkP 活性而言，大多数测试的植物雌激素和工业化学品表现为雌激素受体激动剂。
