Xenoestrogens at picomolar to nanomolar concentrations trigger membrane estrogen receptor-alpha-mediated Ca2+ fluxes and prolactin release in GH3/B6 pituitary tumor cells.
Xenoestrogens at picomolar to nanomolar concentrations trigger membrane estrogen receptor-alpha-mediated Ca2+ fluxes and prolactin release in GH3/B6 pituitary tumor cells.
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DOI：
10.1289/ehp.7505
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发表时间：
2005-04
影响因子：
10.4
通讯作者：
Watson CS
中科院分区：
文献类型：
--
作者：
Wozniak AL;Bulayeva NN;Watson CS
异雌激素（XEs）广泛存在于我们的环境中，并且已知对动物（可能还有人类）种群具有有害影响。作为不适当的雌激素，XE被认为会干扰内源性雌激素，如雌二醇（E2），破坏正常的雌激素信号。我们研究了E2与代表有机氯农药（狄氏剂、硫丹、o′p′-二氯二苯乙烯）、塑料制造副产品/洗涤剂（壬基酚、双酚A）、植物雌激素（香豆雌酚）和合成雌激素（己烯雌酚）的几种XE对垂体肿瘤细胞亚系GH 3/B6/F10的影响，该细胞亚系先前被选择为高水平表达膜雌激素受体-α。皮摩尔至纳摩尔浓度的E2和XEs在给药后30秒内引起细胞内Ca 2+变化。每个XE产生一个独特的时间模式的Ca 2+海拔。从细胞外溶液中去除Ca 2+可消除自发和Xe诱导的细胞内Ca 2+变化，10 μM硝苯地平也是如此。这表明XEs通过质膜中的电压依赖性L型Ca 2+通道介导其作用。没有一个Ca ~（2+）流来自细胞内Ca ~（2+）库。E2和每个XE也引起独特的催乳素（PRL）分泌的时间和浓度依赖性模式，主要是在3分钟内完成的管理。PRL分泌也被硝苯地平阻断，表明Ca 2+内流和PRL分泌之间的相关性。这些数据表明，在非常低的浓度下，XEs介导膜启动的细胞内Ca 2+增加，通过与E2类似的机制导致PRL分泌，但具有不同的模式和效力，可以解释其破坏内分泌功能的能力。
Xenoestrogens (XEs) are widespread in our environment and are known to have deleterious effects in animal (and perhaps human) populations. Acting as inappropriate estrogens, XEs are thought to interfere with endogenous estrogens such as estradiol (E2) to disrupt normal estrogenic signaling. We investigated the effects of E2 versus several XEs representing organochlorine pesticides (dieldrin, endosulfan, o′p′-dichlorodiphenylethylene), plastics manufacturing by-products/detergents (nonylphenol, bisphenol A), a phytoestrogen (coumestrol), and a synthetic estrogen (diethylstilbestrol) on the pituitary tumor cell subline GH3/B6/F10, previously selected for expression of high levels of membrane estrogen receptor-α. Picomolar to nanomolar concentrations of both E2 and XEs caused intracellular Ca2+ changes within 30 sec of administration. Each XE produced a unique temporal pattern of Ca2+ elevation. Removing Ca2+ from the extracellular solution abolished both spontaneous and XE-induced intracellular Ca2+ changes, as did 10 μM nifedipine. This suggests that XEs mediate their actions via voltage-dependent L-type Ca2+ channels in the plasma membrane. None of the Ca2+ fluxes came from intracellular Ca2+ stores. E2 and each XE also caused unique time- and concentration-dependent patterns of prolactin (PRL) secretion that were largely complete within 3 min of administration. PRL secretion was also blocked by nifedipine, demonstrating a correlation between Ca2+ influx and PRL secretion. These data indicate that at very low concentrations, XEs mediate membrane-initiated intracellular Ca2+ increases resulting in PRL secretion via a mechanism similar to that for E2, but with distinct patterns and potencies that could explain their abilities to disrupt endocrine functions.
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影响因子：
4
作者：
Derfoul, A;Lin, FJ;Tuan, RS
通讯作者：
Tuan, RS
影响因子：
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作者：
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作者：
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影响因子：
56.9
作者：
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通讯作者：
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影响因子：
2.7
作者：
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通讯作者：
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