Applied Pharmacology & Toxicology, Inc., C.E.H.T, University of Florida, Department of Physiological Sciences, 2250 NW 24th Ave., Gainesville, Fl 32605, United States.
Regul Toxicol Pharmacol. 2013 Oct;67(1):83-8. doi: 10.1016/j.yrtph.2013.06.007. Epub 2013 Jul 6.
Whether thresholds exist for endocrine active substances and for endocrine disrupting effects of exogenous chemicals has been posed as a question for regulatory policy by the European Union. This question arises from a concern that the endocrine system is too complex to allow estimations of safe levels of exposure to any chemical with potential endocrine activity, and a belief that any such chemical can augment, retard, or disrupt the normal background activity of endogenous hormones. However, vital signaling functions of the endocrine system require it to continuously discriminate the biological information conveyed by potent endogenous hormones from a more concentrated background of structurally similar, endogenous molecules with low hormonal potential. This obligatory ability to discriminate important hormonal signals from background noise can be used to define thresholds for induction of hormonal effects, without which normal physiological functions would be impossible. From such thresholds, safe levels of exposure can be estimated. This brief review highlights how the fundamental principles governing hormonal effects - affinity, efficacy, potency, and mass action - dictate the existence of thresholds and why these principles also define the potential that exogenous chemicals might have to interfere with normal endocrine functioning.
内分泌活性物质和外源性化学物质的内分泌干扰效应是否存在阈值，这已成为欧盟监管政策提出的一个问题。之所以提出这个问题，是因为人们担心内分泌系统过于复杂，无法估计任何具有潜在内分泌活性的化学物质的安全暴露水平，并且认为任何此类化学物质都可能增强、减缓或破坏内源性激素的正常背景活性。然而，内分泌系统的重要信号功能要求其不断区分由强效内源性激素传递的生物信息与具有低激素潜力的结构相似的、内源性分子的更集中背景。这种从背景噪声中区分重要激素信号的强制性能力可用于定义激素效应的阈值，没有这些阈值，正常的生理功能将是不可能的。可以从这些阈值来估计安全的暴露水平。这篇简要综述强调了支配激素效应的基本原则——亲和力、效力、效价和质量作用——如何决定了阈值的存在，以及这些原则如何定义外源性化学物质干扰正常内分泌功能的可能性。
