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首页> 外文期刊>Journal of applied toxicology >Secretion of cortisol and aldosterone as a vulnerable target for adrenal endocrine disruption - screening of 30 selected chemicals in the human H295R cell model.
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Secretion of cortisol and aldosterone as a vulnerable target for adrenal endocrine disruption - screening of 30 selected chemicals in the human H295R cell model.

机译：皮质醇和醛固酮的分泌是肾上腺内分泌破坏的脆弱目标-在人类H295R细胞模型中筛选出30种选定的化学物质。

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摘要

The adrenal gland is a vulnerable target for toxic insult. Disruption of adrenal steroidogenesis and hormone secretion may cause serious effects on human health. A human in vitro model is needed to predict effects, and elucidate mechanisms of endocrine disruption and adrenal toxicity. The human adrenocortical cell line H295R has been used to screen for effects on sex hormones. Here, we have analyzed the effect of 30 potential endocrine disrupting chemicals on the secretion of cortisol and aldosterone from the H295R cells, using specific ELISA assays. The effect of chemicals was analyzed for basal and forskolin- or angiotensin II-stimulated hormone secretion. The chemicals were tested at the highest concentration where they displayed no evident unspecific cytotoxicity. Quantitative and qualitative differences in effects on hormone secretion were demonstrated for the various chemicals. A subset of the chemicals displayed different effects on cortisol and aldosterone secretion, and in some cases the effects were different between basal and stimulated hormone secretion. Aminoglutethimide, prochloraz, ketoconazole, 6-hydroxyflavone, imazalil and etomidate had the most marked inhibitory effects on cortisol (with or without forskolin) and ketoconazole, 6-hydroxyflavone, imazalil and etomidate had the most marked effects on aldosterone (with or without angiotensin II). The results are discussed in terms of known effects, structural similarity and possible mechanisms. We have shown that adrenal steroidogenesis is a vulnerable target for toxic insult and that the H295R assay is a useful in vitro model for screening purposes. Copyright (c) 2008 John Wiley & Sons, Ltd.
机译：肾上腺是毒性侮辱的脆弱目标。肾上腺类固醇生成和激素分泌的破坏可能对人体健康造成严重影响。需要一个体外模型来预测效果，并阐明内分泌干扰和肾上腺毒性的机制。人类肾上腺皮质细胞系H295R已用于筛选对性激素的影响。在这里，我们使用特定的ELISA分析方法分析了30种潜在的破坏内分泌的化学物质对H295R细胞分泌皮质醇和醛固酮的影响。分析了化学物质对基础和福斯高林或血管紧张素II刺激的激素分泌的影响。在最高浓度下测试了这些化学药品，它们没有明显的非特异性细胞毒性。各种化学物质对激素分泌的影响在数量和质量上都得到了证明。这些化学物质的一部分对皮质醇和醛固酮的分泌表现出不同的作用，在某些情况下，基础分泌激素和刺激激素的分泌作用不同。氨基谷氨酰胺，丙草胺，酮康唑，6-羟基黄酮，咪唑和依托咪酯对皮质醇（有或没有福司可林）的抑制作用最明显，而酮康唑，6-羟基黄酮，咪唑和依托咪酯对醛固酮（有或没有血管紧张素Ⅱ的作用最明显） ）。根据已知作用，结构相似性和可能的​​机理讨论了结果。我们已经表明，肾上腺类固醇生成是毒性侮辱的易受攻击目标，并且H295R分析是用于筛选目的的有用的体外模型。版权所有（c）2008 John Wiley＆Sons，Ltd.

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