成年啮齿动物化学暴露后甲状腺激素系统破坏及甲状腺激素血清浓度改变模式——一项系统综述。
完整摘要 · 中文译文
引言：识别甲状腺激素系统干扰物（THSDC）需要充分理解暴露导致甲状腺激素系统（THS）不良结局的机制。 方法：在本系统综述中，我们展示了广泛的证据映射结果，这些结果涉及成年啮齿类动物暴露于各种THSDC后血清或血浆中甲状腺激素（TH）和促甲状腺激素（TSH）的模式。遵循PRISMA指南，我们系统检索了PubMed、Web of Sciences和Scopus中的相关研究。符合条件的研究根据预定义的纳入和排除标准进行筛选。 结果：我们对234项同行评审研究的综述显示，只有一小部分化合物诱导的T4和TSH变化与下丘脑-垂体-甲状腺（HPT）负反馈回路的经典观点一致，而最常见的模式是T4降低而TSH无变化。TSH反应缺失可能是由于T4降低不足以改变HPT反馈。然而，偏倚风险分析还发现了TH/TSH分析方法学的缺陷，包括TH测量时间点，这可能解释研究之间的差异。我们进一步将T4/TSH模式与作用机制信息及其他THS相关结局进行比较，发现THSDC频繁影响TH合成、诱导参与TH代谢的肝酶，并表现出其他药代动力学特性的差异。鉴于各种THSDC的化学性质多样以及分子 对于THS中的靶点，所观察到的不同模式可能没有单一解释。 结论：我们对不同化学暴露后观察到的T4/TSH模式进行的汇编表明，不能仅依赖典型的血清激素模式来确定化学暴露的不利性。具有不同反应的化学物质应被仔细考虑，因为当前的监管标准可能无法将其识别为对人类健康有害。 系统综述注册：https://zenodo.org/records/5528557，标识符 doi.org/10.5281/zenodo.5528557。
完整摘要 · 英文原文
INTRODUCTION: Identification of thyroid hormone system-disrupting chemicals (THSDC) requires a solid understanding of the mechanisms by which exposure leads to adverse outcomes in the thyroid hormone system (THS). METHODS: In this systematic review, we present the results from our extensive evidence mapping of thyroid hormone (TH) and thyroid stimulating hormone (TSH) patterns in serum or plasma, after exposure to various THSDCs in adult rodents. Following PRISMA guidelines, we systematically searched PubMed, Web of Sciences and Scopus for relevant studies. Eligible studies were selected according to predefined inclusion and exclusion criteria. RESULTS: Our review of 234 peer-reviewed studies revealed that only a small group of compounds induced changes in T4 and TSH consistent with the canonical view of the hypothalamic-pituitary-thyroid (HPT) negative feedback loop, whilst the most frequent pattern was a decrease in T4 without TSH changes. The lack of a TSH response may have been due to T4 decreases not being sufficient to change HPT feedback. However, risk of bias analysis also identified deficits in TH/TSH analytical methodology, including the timepoints of TH measurements, possibly explaining discrepancies between studies. We further compared T4/TSH patterns to mechanism-of-action information and other THS-related outcomes and found that THSDCs frequently affected TH synthesis, induced hepatic enzymes involved in TH metabolism, and exhibited other differences in pharmacokinetic properties. Given the diverse chemical nature of the various THSDCs and variety of molecular targets in the THS, there is likely no single explanation for the different patterns observed. CONCLUSION: Our compilation of T4/TSH patterns observed after different chemical exposures demonstrated that it is important to not solely rely on the canonical serum hormonal patterns to determine adversity of chemical exposures. Chemicals with different responses should be carefully considered, as current regulatory criteria may fail to identify them as being harmful to human health. SYSTEMATIC REVIEW REGISTRATION: https://zenodo.org/records/5528557, identifier doi.org/10.5281/zenodo.5528557.