Atrazine-induced changes in aromatase activity in estrogen sensitive target tissues

Atrazine-induced changes in aromatase activity in estrogen sensitive target tissues
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DOI:
10.1002/jat.1275
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发表时间:
2008-04-01
影响因子:
3.3
通讯作者:
Foster, W. G.
Foster, W. G.
中科院分区:
医学4区
文献类型:
--
作者:
Holloway, A. C.;Anger, D. A.;Foster, W. G.

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阿特拉津(ATR)是一种在北美广泛使用的杀虫剂。虽然不直接雌激素,ATR治疗已被证明可以增加肿瘤细胞系中的芳香酶活性。因此,表明ATR可以通过增加芳香化酶活性来增加雌激素敏感靶组织中的局部组织雌激素水平。因此,ATR对芳香酶活性的影响在人颗粒体-叶黄素细胞培养物(大量表达芳香酶的细胞)和子宫内膜基质细胞(ESC)培养物(不表达芳香酶的细胞)中测量。芳香化酶活性进行了定量的氚水方法和测定的特异性进行了确认,通过共孵育与4-羟基雄烯二酮,芳香化酶的催化活性的不可逆抑制剂。ATR处理(1-10 μ m)的granulosa-lutein细胞中的芳香化酶活性与对照培养物相比增加了2倍以上。细胞蛋白中没有处理相关的变化,因此表明ATR诱导的芳香酶活性变化不是由于细胞数量增加。ATR处理在任何测试浓度下对ESC芳香酶活性都没有影响。类似地,ATR处理对我们的无细胞测试系统中的人重组芳香酶活性没有影响。因此,可以得出结论,gm浓度的ATR可以增加人颗粒细胞的芳香化酶活性,但不能增加ESC的芳香化酶活性,并且这种作用在酶水平上不引起。版权所有(C)2007约翰威利父子有限公司
Atrazine (ATR) is a pesticide used widely throughout North America. Although not directly estrogenic, ATR treatment has been shown to increase aromatase activity in tumor cell lines. Thus, it is suggested that ATR can increase local tissue estrogen levels in estrogen sensitive target tissues through increased aromatase activity. Therefore the effect of ATR on aromatase activity was measured in human granulosa-lutein cell cultures, cells that abundantly express aromatase, and endometrial stromal cell (ESC) cultures, cells that do not express aromatase. Aromatase activity was quantified by the tritiated water method and the specificity of the assay was confirmed by co-incubation with 4-hydroxyandrostenedione, an irreversible inhibitor of the catalytic activity of aromatase. Aromatase activity in ATR treated (1-10 mu m) granullosa-lutein cells was increased more than 2-fold compared with control cultures. There were no treatment related changes in cellular protein and thus it is suggested that the ATR-induced change in aromatase activity was not due to an increase in cell number. ATR-treatment had no effect on ESC aromatase activity at any concentration tested. Similarly, there was no effect of ATR treatment on human recombinant aromatase activity in our cell-free test system. Therefore it is concluded that gm concentrations of ATR can increase aromatase activity of human granulosa cells but not ESC and this effect is not elicited at the enzyme level. Copyright (C) 2007 John Wiley & Sons, Ltd.