Atrazine-induced aromatase expression is SF-1 dependent: implications for endocrine disruption in wildlife and reproductive cancers in humans.
Atrazine-induced aromatase expression is SF-1 dependent: implications for endocrine disruption in wildlife and reproductive cancers in humans.
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阿雷津诱导的芳香酶表达是SF-1的依赖性：对野生动植物和人类生殖癌的内分泌破坏的影响。
DOI：
10.1289/ehp.9758
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发表时间：
2007-05
影响因子：
10.4
通讯作者：
Nawata H
中科院分区：
文献类型：
--
作者：
Fan W;Yanase T;Morinaga H;Gondo S;Okabe T;Nomura M;Komatsu T;Morohashi K;Hayes TB;Takayanagi R;Nawata H
阿特拉津是一种有效的内分泌干扰物，可增加某些人类癌细胞系中芳香酶的表达。其机制涉及磷酸二酯酶的抑制和随后 cAMP 的升高。我们比较了阿特拉津反应性和非反应性细胞系中类固醇生成因子 1 (SF-1) 的表达，并将 SF-1 转染到非反应性细胞系中，以评估 SF-1 在阿特拉津诱导的芳香酶中的作用。我们使用由 SF-1 依赖性芳香酶启动子 (ArPII) 驱动的荧光素酶报告基因来检查莠去津和相关西玛津对该启动子的激活作用。我们突变了 SF-1 结合位点以确认 SF-1 的作用。我们还检查了 55 种其他化学品的影响。最后，我们检查了莠去津和西玛嗪与 SF-1 结合以及增强 SF-1 与 ArPII 结合的能力。阿特拉津反应性肾上腺癌细胞 (H295R) 表达的 SF-1 是无反应性卵巢颗粒 KGN 细胞的 54 倍。外源性 SF-1 可使原本无反应的 KGN 和 NIH/3T3 细胞产生莠去津反应性。阿特拉津诱导 SF-1 与染色质结合，ArPII 中 SF-1 结合位点的突变消除了 H295R 细胞中的 SF-1 结合和阿特拉津反应性。在检查的 55 种化学物质中，只有莠去津、西玛津和苯并芘通过 ArPII 诱导荧光素酶。阿特拉津直接与 SF-1 结合，表明阿特拉津是这种“孤儿”受体的配体。目前的研究结果与莠去津对鱼类、两栖动物和爬行动物的内分泌干扰作用一致。在实验室啮齿动物中诱发乳腺癌和前列腺癌；以及莠去津与人类类似生殖癌症之间的相关性。这项研究强调了莠去津作为野生动物内分泌干扰以及实验室啮齿动物和人类生殖癌症风险因素的重要性。
Atrazine is a potent endocrine disruptor that increases aromatase expression in some human cancer cell lines. The mechanism involves the inhibition of phosphodiesterase and subsequent elevation of cAMP. We compared steroidogenic factor 1 (SF-1) expression in atrazine responsive and non-responsive cell lines and transfected SF-1 into nonresponsive cell lines to assess SF-1’s role in atrazine-induced aromatase. We used a luciferase reporter driven by the SF-1–dependent aromatase promoter (ArPII) to examine activation of this promoter by atrazine and the related simazine. We mutated the SF-1 binding site to confirm the role of SF-1. We also examined effects of 55 other chemicals. Finally, we examined the ability of atrazine and simazine to bind to SF-1 and enhance SF-1 binding to ArPII. Atrazine-responsive adrenal carcinoma cells (H295R) expressed 54 times more SF-1 than nonresponsive ovarian granulosa KGN cells. Exogenous SF-1 conveyed atrazine-responsiveness to otherwise nonresponsive KGN and NIH/3T3 cells. Atrazine induced binding of SF-1 to chromatin and mutation of the SF-1 binding site in ArPII eliminated SF-1 binding and atrazine-responsiveness in H295R cells. Out of 55 chemicals examined, only atrazine, simazine, and benzopyrene induced luciferase via ArPII. Atrazine bound directly to SF-1, showing that atrazine is a ligand for this “orphan” receptor. The current findings are consistent with atrazine’s endocrine-disrupting effects in fish, amphibians, and reptiles; the induction of mammary and prostate cancer in laboratory rodents; and correlations between atrazine and similar reproductive cancers in humans. This study highlights the importance of atrazine as a risk factor in endocrine disruption in wildlife and reproductive cancers in laboratory rodents and humans.
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影响因子：
4.1
作者：
Gurates, B;Amsterdam, A;Bulun, SE
通讯作者：
Bulun, SE
影响因子：
3.3
作者：
Eldridge, JC;Wetzel, LT;Tyrey, L
通讯作者：
Tyrey, L
影响因子：
2.4
作者：
Fenelon, JM;Moore, RC
通讯作者：
Moore, RC
影响因子：
5.8
作者：
Agarwal, VR;Bulun, SE;Simpson, ER
通讯作者：
Simpson, ER
影响因子：
3.8
作者：
Cooper, RL;Stoker, TE;McElroy, WK
通讯作者：
McElroy, WK