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证明对胎儿发育和生殖系统具有雌激素作用的化合物。然而，对他们对神经元功能的影响的关注较少。我们已经检查了雌激素污染物对用作Nor义肾上腺神经元模型系统的肾上腺髓质细胞中儿茶酚胺合成的影响。用[ ^<14> c]酪氨酸和酪氨酸羟化酶活性刺激了 ^<14> c-催化胺的合成刺激的 ^<14> c-catecholamine合成3天，用P-氯苯酚和Bisphenol A培养的牛肾上腺髓质细胞处理3天，这一作用并未被ICI 182,780的ICI 182,780，Andogentor and and抑制剂。在0.1 nm处观察到p-北苯酚对 ^<14> c-catecholamine合成的显着影响，比国际监管标准（5 nm）低50倍，最大效应约为10 nm。用10 nM p-北苯酚对细胞的短期治疗10分钟也激活了酪氨酸羟化酶，…更多，它被U0126抑制，U0126是有丝分裂原激活的蛋白激酶（MAPK）激酶的抑制剂。此外，用P-苯酚处理5分钟的细胞以浓度（1-1000 nm）依赖性方式增加了磷酸化p44/42mapk。肾上腺髓质细胞与17β-雌二醇（E_2）（e_2）（0.3-100 nm）或膜上 - 增强E_2-Bovine Serum Serum serum serum Comeuction（100 NM）结合肾上腺髓细胞（E_2）（E_2）（E_2） ^<14> c-catecholamine从[ ^<14> c]酪氨酸中合成。从腺体分离出的质膜显示了[^3H] E_2的两类特定结合位点，明显KDS分别为3.2和106 nm，BMAX和BMAX为0.44和8.5 pmol/mg蛋白。 [^3H] E_2的高亲和力结合受到E_2和植物雌激素的强烈抑制，而其他立体激素则较小，而ICI182,780和环境雌激素污染物则增强了量。这些发现表明，E_2和环境雌激素污染物通过在牛肾上腺髓质的质膜中通过p44/42mapk激活p44/42mapk急性刺激儿茶酚胺的合成。

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

Effect of prolonged exposure to milnacipran on norepinephrine transporter in cultured bovine adrenal medullary cells

长期暴露于米那普仑对培养牛肾上腺髓质细胞去甲肾上腺素转运蛋白的影响