The environmental estrogen bisphenol A stimulates prolactin release in vitro and in vivo.
The environmental estrogen bisphenol A stimulates prolactin release in vitro and in vivo.
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DOI：
10.1210/endo.138.5.5132
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发表时间：
1997-05
期刊：
影响因子：
4.8
通讯作者：
R. Steinmetz;N. G. Brown;D. Allen;R. Bigsby;N. Ben-Jonathan
中科院分区：
文献类型：
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作者：
R. Steinmetz;N. G. Brown;D. Allen;R. Bigsby;N. Ben-Jonathan
环境雌激素（xenoestrogens）是一组模拟雌激素作用的化学物质。双酚A （BPA）是一种用于许多消费品的塑料单体，在体外具有雌激素活性。垂体嗜乳细胞是一种成熟的雌激素反应细胞。总的目的是研究BPA对PRL释放的影响，并探讨其作用机制。具体目的是：1)比较雌二醇和BPA在体外刺激PRL基因表达和释放的效力；2)确定BPA是否会增加体内PRL的释放；3)体内雌激素效应是否由垂体后叶PRL调节因子介导；4)检查BPA是否通过雌激素反应元件（ERE）调节转录。BPA增加了垂体前叶细胞中PRL基因的表达、释放和细胞增殖，尽管其效力比雌二醇低1000到5000倍。另一方面，双酚a对雌激素敏感的Fischer 344 （F344）大鼠诱导高催乳素血症的效果与雌二醇相似；SD大鼠对BPA没有反应。经雌二醇或bpa处理的F344大鼠垂体后叶细胞与稳定转染报告基因的GH3细胞共培养后，PRL基因表达显著增加。与雌二醇类似，BPA在瞬时转染的垂体前、后细胞中诱导ERE活化。我们得出结论：a) BPA模拟雌二醇诱导遗传易感大鼠高泌乳素血症；b)雌二醇和BPA在F344大鼠体内的作用至少部分是通过增加垂体后叶PRL调节因子活性介导的；c) BPA似乎通过ERE调节转录，表明它与垂体前叶和后叶的雌激素受体结合。讨论了BPA和其他异种雌激素对易感人群神经内分泌轴的不利影响的可能性。
Environmental estrogens (xenoestrogens) are a diverse group of chemicals that mimic estrogenic actions. Bisphenol A (BPA), a monomer of plastics used in many consumer products, has estrogenic activity in vitro. The pituitary lactotroph is a well established estrogen-responsive cell. The overall objective was to examine the effects of BPA on PRL release and explore its mechanism of action. The specific aims were to: 1) compare the potency of estradiol and BPA in stimulating PRL gene expression and release in vitro; 2) determine whether BPA increases PRL release in vivo; 3) examine if the in vivo estrogenic effects are mediated by PRL regulating factor from the posterior pituitary; and 4) examine if BPA regulates transcription through the estrogen response element (ERE). BPA increased PRL gene expression, release, and cell proliferation in anterior pituitary cells albeit at a 1000- to 5000-fold lower potency than estradiol. On the other hand, BPA had similar efficacy to estradiol in inducing hyperprolactinemia in estrogen-sensitive Fischer 344 (F344) rats; Sprague Dawley (SD) rats did not respond to BPA. Posterior pituitary cells from estradiol- or BPA-treated F344 rats strongly increased PRL gene expression upon coculture with GH3 cells stably transfected with a reporter gene. Similar to estradiol, BPA induced ERE activation in transiently transfected anterior and posterior pituitary cells. We conclude that: a) BPA mimics estradiol in inducing hyperprolactinemia in genetically predisposed rats; b) the in vivo action of estradiol and BPA in F344 rats is mediated, at least in part, by increasing PRL regulating factor activity in the posterior pituitary; c) BPA appears to regulate transcription through an ERE, suggesting that it binds to estrogen receptors in both the anterior and posterior pituitaries. The possibility that BPA and other xenoestrogens have adverse effects on the neuroendocrine axis in susceptible human subpopulations is discussed.