Endocrine-disrupting chemicals (EDCs) have captivated the attention of scientists, the public and the media [1; 2]. Since its inception, the endocrine disruption field has been controversial [3], and skeptics of the hypothesis have been just as vocal as the proponents. So why should neuroendocrinologists care about EDCs and why have a special issue on the subject? One fundamental reason is because the two fields are inextricably linked. As neuroendocrinologists, our history is already ingrained with the concept that there are critical periods of development, the disruption of which has permanent effects in adulthood. It has been known for decades that exogenous hormones, or interference with endogenous hormones, during these critical periods of organization and activation can have permanent effects on the physiological and behavioral pathways regulated by hypothalamic neuroendocrine circuits. Thus, neuroendocrinologists in some sense predicted that EDCs would disrupt homeostatic neuroendocrine processes, and that the critical developmental periods would be most sensitive, even before the term “endocrine disruptor” was coined. Another more immediate reason is that EDCs are inescapable. For example, EDCs are now recognized to be pervasive in the laboratory. They are present at high levels in soy-based animal feed and in soy supplements consumed by humans, they leach from plastics, lurk in tap water, and can interfere with hormone sensitive assays, such as MCF-7 breast cancer cells, potentially confounding experimental results. They are also common in house dust, fabrics, cookware, furniture, food containers, an assortment of other household products, and even in the air. We are exposed to a complex cocktail of these compounds every day, from conception to death. Just because EDCs pervade our bodies does not automatically mean that they cause harm, and determining which do and which do not, and by what measure, is where the bulk of the controversy now lies. At issue are both the degree to which low dose exposures to chemicals with low hormonal potency can appreciably affect vertebrate physiology, and the degree to which the potential long term risks of chemicals with sex-, life stage-, and tissue-specific impacts can be swiftly and sufficiently gauged. In humans, both issues are difficult to address experimentally because the timing, duration and level of human exposure are often uncertain, particularly during fetal life. Moreover, the latency between EDC exposure and the emergence of consequential health effects can be markedly long, often decades, and the degree to which some groups might be more sensitive than others, resulting in inter-individual variability, is poorly understood. Finally, predicting human responses from sentinel wildlife cases, or experimental animal and in vitro tests of endocrine action is not straightforward and frequently contested [3]. We believe that rapidly emerging data from numerous labs conducting basic animal research, studies of inadvertent human exposures, and epidemiological analyses overwhelmingly point to the inevitable conclusion that EDC exposures are pervasive, and cause both short- and long-term harm to humans and wildlife. But what is the extent of the problem and what should be done to correct it? Neuroendocrinologists are uniquely poised to tackle this question. In this special edition of Frontiers in Neuroendocrinology, eight articles are devoted to the effects of EDCs on reproductive health, neuroendocrine function, thyroid hormones, energy balance, cognition, and maternal behavior in rodents, non-human primates and humans. These articles underscore the message that neuroendocrine disruption, especially during critical periods of the life cycle, can result in a broad array of effects that may not manifest for years or decades. A few highlight recent evidence for transgenerational effects of EDCs [4; 5] and discuss previously unsuspected mechanisms, including molecular epigenetic changes, for the transmission of EDC effects to future generations even if the exposure to the EDC can be identified and removed [Figure 1]. This alarming possibility makes it all the more imperative for neuroendocrinologists to familiarize themselves with the EDC literature and weigh in on the issue. Figure 1 Schematic representation of exposure of neuroendocrine systems in humans to EDCs. Depicted here is how exposure of multiple generations can occur via maternal exposure. EDCs can directly modify the mother’s brain, hormones and the germ cells in ...

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神经内分泌紊乱：历史根源、当前进展、未来问题

内分泌干​​扰化学物质 (EDC) 引起了科学家、公众和媒体的关注 [1; 2]。自成立以来，内分泌干扰领域一直存在争议 [3]，对该假设的怀疑者和支持者一样直言不讳。那么为什么神经内分泌学家应该关心 EDCs 以及为什么对这个主题有一个特殊的问题呢？一个根本原因是因为这两个领域密不可分。作为神经内分泌学家，我们的历史已经根深蒂固地认为存在发育的关键时期，其中断会对成年期产生永久性影响。几十年来，人们都知道外源性激素或干扰内源性激素，在组织和激活的这些关键时期，对下丘脑神经内分泌回路调节的生理和行为途径产生永久性影响。因此，神经内分泌学家在某种意义上预测 EDCs 会破坏稳态的神经内分泌过程，并且关键发育时期将是最敏感的，甚至在“内分泌干扰物”这个术语被创造出来之前。另一个更直接的原因是 EDC 是不可避免的。例如，EDC 现在被认为在实验室中普遍存在。它们在以大豆为基础的动物饲料和人类食用的大豆补充剂中含量很高，它们从塑料中浸出，潜伏在自来水中，并且会干扰激素敏感性测定，例如 MCF-7 乳腺癌细胞，可能会混淆实验结果。它们在室内灰尘、织物、炊具、家具、食品容器、各种其他家居产品甚至空气中也很常见。从受孕到死亡，我们每天都接触到这些化合物的复杂混合物。仅仅因为 EDC 遍布我们的身体并不自动意味着它们会造成伤害，并且确定哪些可以，哪些不可以，以及以什么衡量标准，是目前争论的焦点所在。问题在于低剂量暴露于具有低荷尔蒙效力的化学品对脊椎动物生理的影响程度，以及具有性别、生命阶段和组织特异性影响的化学品的潜在长期风险的程度。迅速而充分地衡量。在人类中，这两个问题都很难通过实验解决，因为时机，人类接触的持续时间和水平通常是不确定的，尤其是在胎儿时期。此外，EDC 暴露和随之而来的健康影响出现之间的潜伏期可能会很长，通常是几十年，并且对某些群体可能比其他群体更敏感的程度，导致个体间差异的程度知之甚少。最后，从哨兵野生动物病例或实验动物和体外内分泌作用测试中预测人类反应并不简单，而且经常有争议[3]。我们相信，来自进行基础动物研究、人类无意暴露研究和流行病学分析的众多实验室迅速涌现的数据绝大多数都指向不可避免的结论，即 EDC 暴露普遍存在，并对人类和野生动物造成短期和长期伤害。但是问题的严重程度如何，应该采取什么措施来纠正它？神经内分泌学家正准备解决这个问题。在这期《神经内分泌学前沿》特刊中，有八篇文章专门讨论 EDC 对啮齿动物、非人类灵长类动物和人类的生殖健康、神经内分泌功能、甲状腺激素、能量平衡、认知和母体行为的影响。这些文章强调了这样一个信息，即神经内分泌紊乱，尤其是在生命周期的关键时期，会导致一系列广泛的影响，这些影响可能在数年或数十年内不会显现出来。一些强调了 EDC 跨代效应的最新证据 [4; 5] 并讨论以前未预料到的机制，包括分子表观遗传变化，用于将 EDC 影响传递给后代，即使可以识别和消除 EDC 的暴露 [图 1]。这种令人担忧的可能性使得神经内分泌学家更需要熟悉 EDC 文献并就这个问题进行权衡。图 1 人体神经内分泌系统暴露于 EDC 的示意图。这里描述的是如何通过母体暴露发生多代暴露。EDCs可以直接改变母亲的大脑、荷尔蒙和生殖细胞…… 图 1 人体神经内分泌系统暴露于 EDC 的示意图。这里描述的是如何通过母体暴露发生多代暴露。EDCs可以直接改变母亲的大脑、荷尔蒙和生殖细胞…… 图 1 人体神经内分泌系统暴露于 EDC 的示意图。这里描述的是如何通过母体暴露发生多代暴露。EDCs可以直接改变母亲的大脑、荷尔蒙和生殖细胞……