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类固醇生成的破坏:用于机制研究和作为筛选工具的细胞模型。

Disruption of steroidogenesis: Cell models for mechanistic investigations and as screening tools.

作者信息

Odermatt Alex, Strajhar Petra, Engeli Roger T

机构信息

Swiss Center for Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, Pharmacenter, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.

Swiss Center for Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, Pharmacenter, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.

出版信息

J Steroid Biochem Mol Biol. 2016 Apr;158:9-21. doi: 10.1016/j.jsbmb.2016.01.009. Epub 2016 Jan 22.

Abstract

In the modern world, humans are exposed during their whole life to a large number of synthetic chemicals. Some of these chemicals have the potential to disrupt endocrine functions and contribute to the development and/or progression of major diseases. Every year approximately 1000 novel chemicals, used in industrial production, agriculture, consumer products or as pharmaceuticals, are reaching the market, often with limited safety assessment regarding potential endocrine activities. Steroids are essential endocrine hormones, and the importance of the steroidogenesis pathway as a target for endocrine disrupting chemicals (EDCs) has been recognized by leading scientists and authorities. Cell lines have a prominent role in the initial stages of toxicity assessment, i.e. for mechanistic investigations and for the medium to high throughput analysis of chemicals for potential steroidogenesis disrupting activities. Nevertheless, the users have to be aware of the limitations of the existing cell models in order to apply them properly, and there is a great demand for improved cell-based testing systems and protocols. This review intends to provide an overview of the available cell lines for studying effects of chemicals on gonadal and adrenal steroidogenesis, their use and limitations, as well as the need for future improvements of cell-based testing systems and protocols.

摘要

在现代世界中,人类一生都暴露于大量合成化学物质中。其中一些化学物质有可能干扰内分泌功能,并促使重大疾病的发生和/或发展。每年约有1000种用于工业生产、农业、消费品或作为药物的新型化学物质进入市场,而对于其潜在内分泌活性的安全性评估往往有限。类固醇是重要的内分泌激素,类固醇生成途径作为内分泌干扰化学物质(EDC)的作用靶点,已得到顶尖科学家和权威机构的认可。细胞系在毒性评估的初始阶段发挥着重要作用,即用于机理研究以及对具有潜在类固醇生成干扰活性的化学物质进行中高通量分析。然而,使用者必须意识到现有细胞模型的局限性,以便正确应用它们,并且对改进基于细胞的检测系统和方案有很大需求。本综述旨在概述用于研究化学物质对性腺和肾上腺类固醇生成影响的现有细胞系、它们的用途和局限性,以及对基于细胞的检测系统和方案未来改进的需求。

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