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Testing for thyroid hormone disruptors, a review of non-mammalian in vivo models.
Molecular and Cellular Endocrinology ( IF 3.8 ) Pub Date : 2020-03-06 , DOI: 10.1016/j.mce.2020.110779
Stephan Couderq 1 , Michelle Leemans 1 , Jean-Baptiste Fini 1
Affiliation  

Thyroid hormones (THs) play critical roles in profound changes in many vertebrates, notably in mammalian neurodevelopment, although the precise molecular mechanisms of these fundamental biological processes are still being unravelled. Environmental and health concerns prompted the development of chemical safety testing and, in the context of endocrine disruption, identification of thyroid hormone axis disrupting chemicals (THADCs) remains particularly challenging. As various molecules are known to interfere with different levels of TH signalling, screening tests for THADCs may not rely solely on in vitro ligand/receptor binding to TH receptors. Therefore, alternatives to mammalian in vivo assays featuring TH-related endpoints that are more sensitive than circulatory THs and more rapid than thyroid histopathology are needed to fulfil the ambition of higher throughput screening of the myriad of environmental chemicals. After a detailed introduction of the context, we have listed current assays and parameters to assess thyroid disruption following a literature search of recent publications referring to non-mammalian models. Potential THADCs were mostly investigated in zebrafish and the frog Xenopus laevis, an amphibian model extensively used to study TH signalling.

中文翻译:

测试甲状腺激素破坏剂,非哺乳动物体内模型的综述。

甲状腺激素(THs)在许多脊椎动物的深刻变化中起着至关重要的作用,特别是在哺乳动物的神经发育中,尽管这些基本生物学过程的确切分子机制仍未阐明。对环境和健康的关注促使化学安全性测试的发展,在内分泌干扰的情况下,鉴定甲状腺激素轴破坏性化学物质(THADCs)仍然特别具有挑战性。由于已知各种分子会干扰不同水平的TH信号传导,因此THADC的筛选测试可能不仅仅依赖于与TH受体的体外配体/受体结合。因此,为了实现对多种环境化学物质进行更高通量筛选的雄心壮志,需要具有与循环TH相比更敏感,比甲状腺组织病理学更快的TH相关终点的哺乳动物体内试验的替代方法。在对上下文进行详细介绍之后,我们在参考非哺乳动物模型的最新出版物进行文献检索之后,列出了当前的测定方法和参数,以评估甲状腺功能衰竭。潜在的THADC主要在斑马鱼和青蛙Xenopus laevis(两栖动物模型,广泛用于研究TH信号转导)中进行了研究。我们在参考非哺乳动物模型的最新出版物进行文献检索之后,列出了当前的测定方法和参数,以评估甲状腺功能衰竭。潜在的THADC主要在斑马鱼和青蛙Xenopus laevis(两栖动物模型,广泛用于研究TH信号转导)中进行了研究。我们在参考非哺乳动物模型的最新出版物进行文献检索之后,列出了当前的测定方法和参数,以评估甲状腺功能衰竭。潜在的THADC主要在斑马鱼和青蛙Xenopus laevis(两栖动物模型,广泛用于研究TH信号转导)中进行了研究。
更新日期:2020-03-06
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