Atrazine Binds to the Growth Hormone-Releasing Hormone Receptor and Affects Growth Hormone Gene Expression
Atrazine Binds to the Growth Hormone-Releasing Hormone Receptor and Affects Growth Hormone Gene Expression
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DOI：
10.1289/ehp.0900738
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发表时间：
2010-10-01
影响因子：
10.4
通讯作者：
Trail, Frances
中科院分区：
文献类型：
--
作者：
Fakhouri, Walid D.;Nunez, Joseph L.;Trail, Frances
背景：阿特拉津(Atrazine，ATR)是美国常用的除草剂，由于其在生态系统中的移动性和在环境中的持久性，在水和土壤中广泛分布。ATR一直与动物性发育缺陷有关，但对哺乳动物系统的研究未能明确确定细胞靶点。目的：本研究的目的是在基因表达水平上确定垂体细胞中ATR的配体结合受体，从而从基因表达水平解释ATR的作用机制。方法：我们利用出生后7d的雄性大鼠的垂体细胞和垂体细胞系，从RNA和蛋白质水平研究ATR对生长激素(GH)、黄体生成素(LH)和催乳素(PRL)基因表达的影响。用C-14-ATR测定其与生长激素释放激素受体(GHRHR)的特异性结合。结果：环境相关浓度(1ppb和1ppm)的ATR处理大鼠垂体细胞后，GH表达下降。这种作用可能是由于ATR与垂体细胞的GHRHR结合而抑制了GH基因的转录。结论：将GHRHR确定为ATR的靶标与先前报道的ATR在哺乳动物系统中的多种作用是一致的。这些发现可能会导致更好地了解环境ATR污染的危害，并为制定建立水系统安全水平的指导方针提供参考。
BACKGROUND: Atrazine (ATR), a commonly used herbicide in the United States, is widely distributed in water and soil because of its mobility through ecosystems and its persistence in the environment. ATR has been associated with defects in sexual development in animals, but studies on mammalian systems have failed to clearly identify a cellular target.OBJECTIVES: Our goal in this study was to identify a ligand-binding receptor for ATR in pituitary cells that may explain the mechanism of action at the gene expression level.METHODS: We used pituitary cells from postnatal day 7 male rats and pituitary cell lines to study the effect of ATR on gene expression of growth hormone (GH), luteinizing hormone (LH), and prolactin (PRL) at RNA and protein levels. C-14-ATR was used to determine its specific binding to the growth hormone-releasing hormone receptor (GHRHR). The effect of ATR on structural proteins was visualized using immunofluorescent in situ staining.RESULTS: The treatment of rat pituitary cells with ATR, at environmentally relevant concentrations (1 ppb and 1 ppm), resulted in a reduction of GH expression. This effect appeared to result from the inhibition of GH gene transcription due to ATR binding to the GHRHR of the pituitary cells.CONCLUSIONS: Identification of GHRHR as the target of ATR is consistent with the myriad effects previously reported for ATR in mammalian systems. These findings may lead to a better understanding of the hazards of environmental ATR contamination and inform efforts to develop guidelines for establishing safe levels in water systems.