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Mechanisms of Reproductive Toxicity by Endocrine Disrupting Chemicals

内分泌干扰物的生殖毒性机制

基本信息

批准号：
11307007
负责人：
TOKUNAGA Rikio
金额：
$ 18.17万
依托单位：
Kansai Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11307007/
关键词：
Endocrine Disrupting Chemicals Reproductive Toxicity Estrogen 内分泌撹乱物質

项目摘要

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.

为了评估内分泌干扰物质对人类生殖功能的影响，我们重点研究了通过食物摄入的植物雌激素。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MCF-7细胞中起“超级激动剂”的作用，这在本研究中得到了证实。而在HeLa细胞和COS-7细胞中，白藜芦醇的最大激活作用低于雌二醇。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。柚皮素的最佳活化浓度也存在差异。研究了白藜芦醇是否具有拮抗剂作用。在我们使用的所有报告系统中，没有检测到白藜芦醇的拮抗活性。白藜芦醇和雌二醇在COS-7细胞和酵母细胞中表现为加性作用，而在293细胞中表现为协同作用。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包括酵母在内的所有报告基因分析系统中都表现出加性效应。我们的研究表明，结构多样的植物雌激素的雌激素活性和抗雌激素活性是复杂和不可预测的。为了筛选饮料中可能存在的雌激素成分，我们制备了啤酒啤酒花和草药茶混合物的提取物，并测定了它们的雌激素活性。两种啤酒花和四种草药茶的混合物具有积极的效果。这些草药茶混合物中所含的常见成分是甘草根。