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Effects of environmental estrogenic pollutants on cellular functions in the noradrenergic neurons and search for their receptors

环境雌激素污染物对去甲肾上腺素能神经元细胞功能的影响及其受体的寻找

基本信息

批准号：
17590111
负责人：
TAKAHASHI Kojiro
金额：
$ 2.24万
依托单位：
University of Occupational and Environmental Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Environmental estrogenic pollutants are compounds that have been shown to have estrogenic effects on fetal development and reproductive systems. Less attention, however, has been paid to their influence on neuronal functions. We have examined the effects of estrogenic pollutants on catecholamine synthesis in adrenal medullary cells used as a model system of noradrenergic neurons. Treatment of cultured bovine adrenal medullary cells with p-nonylphenol and bisphenol A at 10 nM for 3 days stimulated ^<14>C-catecholamine synthesis from [^<14>C]tyrosine and tyrosine hydroxylase activity, an effect that was not inhibited by ICI 182,780, an inhibitor of estrogen receptors. Significant effects of p-nonylphenol on ^<14>C-catecholamine synthesis were observed at 0.1 nM that is 50 times lower than that of the international regulatory standard (5 nM) and the maximum effects were around at 10 nM. Short-term treatment of cells with 10 nM p-nonylphenol for 10 min also activated tyrosine hydroxylase, … More which was suppressed by U0126, an inhibitor of mitogen-activated protein kinase (MAPK) kinase. Furthermore, treatment of cells with p-nonylphenol for 5 min increased the phospho-p44/42MAPK in a concentration (1 - 1000 nM)-dependent manner.Incubation of adrenal medullary cells with 17β-estradiol(E_2) (0.3-100 nM) or membrane-impermeable E_2-bovine serum albumin (100 nM) also acutely increased ^<14>C-catecholamine synthesis from [^<14>C]tyrosine. The plasma membrane isolated from the gland showed two classes of specific binding sites of [^3H] E_2 with apparent Kds of 3.2 and 106 nM and Bmaxs of 0.44 and 8.5 pmol/mg protein, respectively. The high-affinity binding of [^3H] E_2 was most strongly inhibited by E_2 and phytoestrogens, and to lesser extents by other steroid hormones, while it was enhanced by ICI182,780 and environmental estrogenic pollutants.These findings suggest that E_2 and environmental estrogenic pollutants acutely stimulates catecholamine synthesis via activation of p44/42MAPK through unique estrogen receptors in the plasma membrane of bovine adrenal medulla. Less

环境雌激素污染物是已被证明对胎儿发育和生殖系统具有雌激素效应的化合物。然而，很少有人注意到它们对神经元功能的影响。我们研究了雌激素污染物对肾上腺髓质细胞（以去甲肾上腺素能神经元为模型系统）儿茶酚胺合成的影响。用浓度为10 nM的对壬基酚和双酚A处理培养的牛肾上腺髓质细胞3天，可<14>刺激[^<14>C]酪氨酸和酪氨酸羟化酶活性合成^C-儿茶酚胺，这种作用不受雌激素受体抑制剂ICI 182，780的抑制。在0.1 nM下观察到对壬基苯酚对β-<14>C-儿茶酚胺合成的显著影响，其比国际监管标准（5 nM）低50倍，并且最大影响在10 nM左右。用10 nM对壬基苯酚短期处理细胞10分钟也激活酪氨酸羟化酶， ...更多信息而丝裂原活化蛋白激酶（MAPK）抑制剂U 0126则能抑制该作用。此外，对壬基苯酚处理细胞5 min，磷酸化p44/42 MAPK以浓度（1 - 1000 nM）依赖性方式增加。肾上腺髓细胞与17β-雌二醇（E_2）（0.3-100 nM）或膜不可渗透的E_2-牛血清白蛋白（100 nM）孵育也急剧增加<14>[^ C]酪氨酸的^C-儿茶酚胺合成<14>。从腺体分离的质膜显示两类[^3H] E_2的特异性结合位点，表观Kd值分别为3.2和106 nM，Bmax值分别为0.44和8.5 pmol/mg蛋白。E_2和植物雌激素对[^3H] E_2的高亲和力结合抑制作用最强，其它甾体激素对[^3H] E_2的抑制程度较小，而ICI 182则增强了[^3H] E_2的高亲和力结合，这些结果提示E_2和环境雌激素污染物通过激活p44/42 MAPK通过牛肾上腺髓质质膜上独特的雌激素受体。少

项目成果

期刊论文数量（32）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nephrogenic diabetes insipidus in mice lacking all nitric oxide synthase isoforms

DOI：
10.1073/pnas.0502236102
发表时间：
2005-07-26
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Morishita, T;Tsutsui, M;Yanagihara, N
通讯作者：
Yanagihara, N

Effects of nitric oxide synthase isoform deletion on oxytocin and vasopressin messenger RNA in mouse hypothalamus.

一氧化氮合酶亚型缺失对小鼠下丘脑催产素和加压素信使 RNA 的影响。