期刊
ENVIRONMENTAL HEALTH PERSPECTIVES
卷 113, 期 4, 页码 431-439出版社
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.7505
关键词
bisphenol A; coumestrol; DDE; DES; diethylstilbestrol; dieldrin; endosulfan; estrogen receptor-alpha; exocytosis; L-type channels; membrane; nonylphenol; phytoestrogen; prolactin; xenoestrogen
资金
- NIEHS NIH HHS [R01 ES010987] Funding Source: Medline
- PHS HHS [010987] Funding Source: Medline
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 (E-2) to disrupt normal estrogenic signaling. We investigated the effects of E-2 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-alpha. Picomolar to nanomolar concentrations of both E-2 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 mu M 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. E-2 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 E-2, but with distinct patterns and potencies that could explain their abilities to disrupt endocrine functions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据