Assessing estrogenic activity of phytochemicals using transcriptional activation and immature mouse uterotrophic responses
Assessing estrogenic activity of phytochemicals using transcriptional activation and immature mouse uterotrophic responses
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DOI：
10.1016/s1570-0232(02)00493-2
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发表时间：
2002-09-25
影响因子：
3
通讯作者：
Newbold, RR
中科院分区：
文献类型：
--
作者：
Jefferson, WN;Padilla-Banks, E;Newbold, RR
使用测量雌激素受体 (ER) 转录激活的体外测定和包括测量子宫湿重增加以及敏感形态和生化终点的体内未成熟小鼠子宫营养测定，在宽剂量范围内比较了几种植物雌激素（包括染料木素、大豆黄酮、香豆雌酚、α-玉米赤霉醇、玉米赤霉烯酮、柚皮素、花旗松素和生物鸡宁 A）的雌激素反应。在子宫里。转录激活测定显示除花旗松素外的所有测试化合物均激活 ER，与雌二醇或己烯雌酚相比，其反应程度不同。促子宫生物测定结果表明，金雀异黄酮、香豆雌酚、玉米赤霉醇和玉米赤霉烯酮会导致子宫湿重增加，而柚皮素、花旗松素、大豆苷元和生物鸡豆芽素 A 在测试的剂量范围内则没有这种作用。然而，敏感的形态学和生化参数，如子宫上皮细胞高度增加、子宫腺体数量增加和雌激素反应蛋白乳铁蛋白的诱导，表明本研究中测试的所有化合物都具有一定的雌激素活性，尽管化合物之间显示出广泛的雌激素反应。本文所述的多种体外和体内雌激素终点的使用将有助于开发单个化合物和最终化合物混合物的雌激素谱。此外，每种植物化学物质的雌激素“指纹”是确定接触植物雌激素潜在不利影响的重要第一步。 (C) 2002 Elsevier Science B.V. 保留所有权利。
The estrogenic responses of several phytoestrogens including genistein, daidzein, coumestrol, alpha-zearalanol, zearalenone, naringenin, taxifolin and biochanin A were compared over a wide dose range using an in vitro assay that measures transcriptional activation of the estrogen receptor (ER) and an in vivo immature mouse uterotrophic assay consisting of measuring uterine wet weight increase plus sensitive morphological and biochemical endpoints in the uterus. The transcriptional activation assay showed activation of the ER by all compounds tested except taxifolin with varying magnitudes of response as compared to estradiol or diethylstilbestrol. Results from the uterotropic bioassay showed that genistein, coumestrol, zearalanol, and zearalenone caused an increase in uterine wet weight, while naringenin, taxifolin, daidzein and biochanin A failed to do so over the dose range tested. However, sensitive morphological and biochemical parameters such as uterine epithelial cell height increase, uterine gland number increase, and induction of the estrogen-responsive protein lactoferrin demonstrated that all compounds tested in this study gave some measure of estrogenicity although a wide range of estrogenic responses across compounds was shown. Use of multiple in vitro and in vivo estrogenic endpoints as described in this paper will be useful in developing estrogenic profiles for individual compounds and ultimately mixtures of compounds. Furthermore, having an estrogenic "fingerprint" for each phytochemical is an essential first step in determining potential adverse effects of exposure to phytoestrogens. (C) 2002 Elsevier Science B.V. All rights reserved.