Słomczyńska M
Department of Endocrinology and Tissue Culture, Institute of Zoology, Jagiellonian University, Ingardena 6, 30-060 Krakow, Poland.
Pol J Vet Sci. 2008;11(3):263-9.
Xenoestrogens are defined as chemicals that mimic some structural parts of the physiological estrogen compounds, therefore may act as estrogens or could interfere with the actions of endogenous estrogens. Two subtypes of the ER are known, the ER alpha and ER beta, and both have a distinct tissue distribution and play a distinct role in physiology. Receptor dimmer assumes a distinctive conformation, binds to its estrogen response element (ERE), interacts with the general transcription complex bound to the TATA box within the respective gene promoter, and regulates gene transcription. The discovery and identification of co-activators and co-repressors provided crucial insights into the ER action. New evidence indicates that the activation of additional transcription factors as well as the action of xenoestrogens through estrogen receptors located outside the cell nucleus (in the plasma membrane, mitochondria and probably the cytosol) should be considered. The levels of exposition to xenoestrogens and the age of the investigated animal can have a significant effect on its development and reproduction. Therefore, several in vivo and in vitro assays have been developed to assess the estrogenic-like activity of individual compounds or natural mixtures. In this review, selected methods applied in physiological studies have been described. One of the most extensively used in vivo assays for estrogenicity is the rodent uterotrophic assay. In order to analyze the estrogenic properties of xenoestrogens, morphological, histological, biochemical and molecular studies should be introduced. A variety of in vitro tests have been established to determine estrogenic potency of xenoestrogens but even a combination of them is not able to predict their actual action in the organism. There is a need for the studies on all potential xenoestrogens to describe tissue-specific activities, and via which pathways in those tissues these compounds either disrupt or mimic hormone action.
外源性雌激素被定义为能够模拟生理性雌激素化合物某些结构部分的化学物质,因此可能充当雌激素或干扰内源性雌激素的作用。已知雌激素受体(ER)有两种亚型,即ERα和ERβ,它们在组织中的分布不同,在生理学中发挥着不同的作用。受体二聚体呈现独特的构象,与雌激素反应元件(ERE)结合,与结合在各自基因启动子内TATA盒上的通用转录复合体相互作用,并调节基因转录。共激活因子和共抑制因子的发现与鉴定为ER的作用提供了关键见解。新证据表明,还应考虑其他转录因子的激活以及外源性雌激素通过位于细胞核外(质膜、线粒体以及可能还有细胞质)的雌激素受体所产生的作用。外源性雌激素的暴露水平以及所研究动物的年龄对其发育和繁殖可能有显著影响。因此,已经开发了几种体内和体外试验来评估单个化合物或天然混合物的雌激素样活性。在这篇综述中,描述了生理研究中应用的一些选定方法。用于雌激素活性检测的最广泛使用的体内试验之一是啮齿动物子宫增重试验。为了分析外源性雌激素的雌激素特性,应引入形态学、组织学、生物化学和分子研究。已经建立了多种体外试验来确定外源性雌激素的雌激素效力,但即使将它们组合起来也无法预测其在生物体中的实际作用。有必要对所有潜在的外源性雌激素进行研究,以描述其组织特异性活性,以及这些化合物在那些组织中通过哪些途径破坏或模拟激素作用。