Mechanisms of Reproductive Toxicity by Endocrine Disrupting Chemicals

为了评估内分泌干扰化学物质对人类生殖功能的影响，我们重点关注通过食物摄入吸收的植物雌激素。我们测试了两种植物雌激素——白藜芦醇和柚皮素——的雌激素和抗雌激素作用。据报道，白藜芦醇在人类 MCF-7 细胞中充当“超级激动剂”，这一点在本研究中得到证实。然而，在HeLa细胞或COS-7细胞中，白藜芦醇的最大激活低于雌二醇的最大激活。在酵母中，最大激活所需的白藜芦醇浓度比 MCF-7 细胞高 50 倍，而最佳雌二醇浓度没有差异。对于柚皮素也观察到最大激活的最佳浓度的差异。研究了白藜芦醇是否充当拮抗剂。在我们使用的所有报告分析系统中均未检测到白藜芦醇的拮抗活性。白藜芦醇和雌二醇在 COS-7 或酵母细胞中表现出相加效应，而在 293 细胞中观察到协同效应。与白藜芦醇和雌二醇之间复杂的相互作用相反，柚皮素和雌二醇在我们使用的所有报告分析系统（包括酵母）中表现出相加效应。我们的研究表明，结构多样的植物雌激素的雌激素和抗雌激素活性是复杂且不可预测的。为了筛选饮料中可能存在的雌激素成分，我们制备了啤酒花和花草茶混合物的提取物，并测定了它们的雌激素活性。两种啤酒花和四种香草茶混合物产生了积极的结果。仅在这些花草茶混合物中含有的常见成分是甘草根。

To evaluate the effects of endocrine disrupting chemicals on reproductive functions in human beings, we focused on phytoestrogens that are taken up through food intake. We tested the estrogenic and antiestrogenic effects of two phytoestrotens, resveratrol and naringenin. Resveratrol is reported to act as a "super agonist" in human MCF-7 cells, which was confirmed in the present study. However, in HeLa cells or COS-7 cells, the maximal activation by resveratrol was lower than that by estradiol. In yeast, the resveratrol concentration required for the maximal activation was 50-fold higher than in MCF-7 cells, while there was no difference in optimal estradiol concentrations. Difference in optimal concentration for the maximal activation was observed also observed for naringenin. Whether resveratrol acts as an antagonist was investigated. No antagonistic activity was detected with resveratrol in all reporter assay systems we used. Resveratrol and estradiol exhibited an additive effect in COS-7 or yeast cells, whereas synergistic effect was observed in 293 cells. In contrast to the complex interactions between resveratrol and estradiol, naringenin and estradiol exhibited additive effect in all reporter assay systems we used including yeast. Our study indicates that estrogenic and antiestrogenic activity of structurally diverse phytoestrogens is complex and unpredictable. To screen the estrogenic ingredients, possibly found in beverages, we prepared the extracts from beer hops and herb tea mixtures and determined their estrogenic activities. Two hops and four herb tea mixtures gave positive results. The common ingredients contained only in those herb tea mixtures was liquorice root.