Environmental toxicant effects on neuroendocrine function
Environmental toxicant effects on neuroendocrine function
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DOI：
10.1385/endo:14:2:235
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发表时间：
2001-03-01
期刊：
影响因子：
3.7
通讯作者：
Gore, AC
中科院分区：
文献类型：
--
作者：
Gore, AC
暴露于环境毒物会对正常生长和发育产生深远影响。然而，这些有毒物质发挥这些作用的机制还不清楚。许多环境毒物改变生殖功能，并对中枢神经系统和行为产生影响，但这些生殖和神经现象之间的联系尚未得到系统的研究。神经内分泌（下丘脑-垂体-性腺）轴整合神经和生殖系统的输入和输出，在功能和解剖学上介导环境毒物，特别是内分泌干扰化学品（EDCs）对发育过程的影响。本文综述了EDC对神经内分泌系统的影响，特别是在下丘脑促性腺激素释放激素（GnRH）神经元，参与生殖功能调节的关键细胞的水平上的当前文献。本文重点介绍了两种多氯联苯混合物（多氯联苯1221、多氯联苯1254）和两种有机氯农药（甲氧滴滴涕和毒死蜱）。本文介绍了四种城市环境毒物对GnRH细胞的体外和体内作用的实验数据。体外实验的结果表明，所有四种毒物深刻地影响下丘脑GnRH基因表达，细胞存活和神经突生长，证明了对GnRH细胞系的EDCs的直接影响。在体内实验中，三种毒物（多氯联苯1221，甲氧滴滴涕，毒死蜱）引起雌性大鼠GnRH mRNA水平的显着改变。体外和体内研究结果都支持毒死蜱作为EDC的新概念。这些结果与文献一起支持了神经内分泌轴，特别是GnRH神经元对城市环境毒物敏感的假设，并且内分泌干扰物的生殖和神经效应可能在下丘脑-垂体-性腺轴的这一水平上介导。
Exposure to environmental toxicants can have profound effects on normal growth and development. However, the mechanisms by which these toxicants exert these effects are not well understood. Many environmental toxicants alter reproductive function and have effects on the central nervous system and behavior, yet the link between these reproductive and neurologic phenomena has not been systematically investigated. The neuroendocrine (hypothalamic-pituitary-gonadal) axis, which integrates inputs to and outputs from the nervous and reproductive systems, is functionally and anatomically situated to mediate effects of environmental toxicants, particularly those that are endocrine-disrupting chemicals (EDCs), on developmental processes. This article reviews the current literature on EDC effects on the neuroendocrine system, particularly at the level of hypothalamic gonadotropin-releasing hormone (GnRH) neurons, the key cells involved in the regulation of reproductive function. The focus of this article is on two polychlorinated biphenyl mixtures (Aroclor 1221, Aroclor 1254) and two organochlorine pesticides (methoxychlor and chlorpyrifos). Some experimental data are presented for each of the four urban environmental toxicants on GnRH cells in vitro and in vivo. The results of in vitro experiments indicate that all four of the toxicants profoundly affect hypothalamic GnRH gene expression, cell survival, and neurite outgrowth, demonstrating direct effects of EDCs on a GnRH cell line. In in vivo experiments, three of the toxicants (Aroclor 1221,methoxychlor, and chlorpyrifos) caused significant alterations in GnRH mRNA levels in female rats. Both the in vitro and in vivo findings support the novel concept of chlorpyrifos as an EDC. The results, taken together with the literature, support the hypothesis that the neuroendocrine axis, and specifically GnRH neurons, are sensitive to urban environmental toxicants, and that reproductive and neurologic effects of EDCs may be mediated at this level of the hypothalamic-pituitary-gonadal axis.