Fraunhofer IME, Department of Ecotoxicology, Schmallenberg, Germany.
Fraunhofer ITEM, Department of Chemical Risk Assessment, Hannover, Germany.
Environ Toxicol Chem. 2018 Feb;37(2):318-328. doi: 10.1002/etc.3995. Epub 2017 Dec 13.
To be defined as an endocrine disruptor, a substance has to meet several criteria, including the induction of specific adverse effects, a specific endocrine mode of action, and a plausible link between both. The latter criterion in particular might not always be unequivocally determined, especially because the endocrine system consists of diverse endocrine axes. The axes closely interact with each other, and manipulation of one triggers effects on the other. The present review aimed to identify some of the many interconnections between these axes. The focus was on fish, but data obtained in studies on amphibians and mammals were considered if they assisted in closing data gaps, because most of the endocrine mechanisms are evolutionarily conserved. The review includes data both from ecotoxicological studies and on physiological processes and gives information on hormone/hormone receptor interactions or gene transcription regulation. The key events and key event relationships identified provide explanations for unexpected effects on one axis, exerted by substances suspected to act specifically on another axis. Based on these data, several adverse outcome pathway (AOP) segments are identified, describing connections between the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) axes, the HPG and hypothalamic-pituitary-adrenal/interrenal (HPA/I) axes, and the HPT and HPA/I axes. Central key events identified across axes were altered aromatase activity as well as altered expression and function of the proteins 11β-hydroxysteroid dehydrogenase (11β-HSD) and steroidogenic acute regulatory (StAR) protein. Substance classes that act on more than one endocrine axis were, for example, goitrogens or aromatase inhibitors. Despite the wealth of information gathered, the present review only provides a few insights into the molecular nets of endocrine axes, demonstrating the complexity of their interconnections. Environ Toxicol Chem 2018;37:318-328. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
要被定义为内分泌干扰物，一种物质必须满足几个标准，包括诱导特定的不良反应、特定的内分泌作用模式以及两者之间的合理联系。特别是后一个标准并不总是能够明确确定，特别是因为内分泌系统由多种内分泌轴组成。这些轴相互密切相互作用，对一个轴的操纵会触发对另一个轴的影响。本综述旨在确定这些轴之间的一些许多相互联系。重点是鱼类，但如果在研究两栖动物和哺乳动物的研究中获得的数据有助于填补数据空白，也会考虑这些数据，因为大多数内分泌机制在进化上是保守的。该综述包括来自生态毒理学研究的数据以及关于生理过程的信息，并提供了激素/激素受体相互作用或基因转录调节的信息。确定的关键事件和关键事件关系为由于怀疑对另一轴起特异性作用的物质对一个轴产生的意外影响提供了解释。基于这些数据，确定了几个不良结果途径 (AOP) 片段，描述了下丘脑-垂体-性腺 (HPG) 和下丘脑-垂体-甲状腺 (HPT) 轴、HPG 和下丘脑-垂体-肾上腺/间肾 (HPA/I) 轴以及 HPT 和 HPA/I 轴之间的连接。跨轴确定的中心关键事件是芳香酶活性改变以及 11β-羟类固醇脱氢酶 (11β-HSD) 和类固醇急性调节蛋白 (StAR) 蛋白的表达和功能改变。作用于多个内分泌轴的物质类别例如，甲状腺肿原或芳香酶抑制剂。尽管收集了丰富的信息，但本综述仅提供了对内分泌轴分子网络的一些了解，展示了它们相互联系的复杂性。环境毒物化学 2018；37:318-328。© 2017 作者。环境毒物化学由 Wiley 期刊出版，代表 SETAC 出版。
