Institute of Medical Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Northern Ireland BT9 5DL, UK.
Environ Int. 2021 Feb;147:106311. doi: 10.1016/j.envint.2020.106311. Epub 2020 Dec 18.
The insulin-like growth factor (IGF) system is a critical regulator of growth, especially during fetal development, while also playing a central role in metabolic homeostasis. Endocrine disruptors (EDs) are ubiquitous compounds able to interfere with hormone action and impact human health. For example, exposure to EDs is associated with decreased birthweight and increased incidence of metabolic disorders. Therefore, the IGF system is a potential target for endocrine disruption. This review summarises the state of the science regarding effects of exposure to major classes of endocrine disruptors (dioxins and dioxin-like compounds, polycyclic aromatic hydrocarbons, polybrominated diphenyl ethers, phthalates, perfluoroalkyl substances and bisphenol A) on the IGF system. Evidence from both experimental models (in vitro and in vivo) and epidemiological studies is presented. In addition, possible molecular mechanisms of action and effects on methylation are discussed. There is a large body of evidence supporting the link between dioxins and dioxin-like compounds and IGF disruption, but mixed findings have been reported in human studies. On the other hand, although only a few animal studies have investigated the effects of phthalates on the IGF system, their negative association with IGF levels and methylation status has been more consistently reported in humans. For polybrominated diphenyl ethers, perfluoroalkyl substances and bisphenol A the evidence is still limited. Despite a lack of studies for some ED classes linking ED exposure to changes in IGF levels, and the need for further research to improve reproducibility and determine the degree of risk posed by EDs to the IGF system, this is clearly an area of concern.
胰岛素样生长因子 (IGF) 系统是生长的关键调节剂，特别是在胎儿发育期间，同时在代谢稳态中也起着核心作用。内分泌干扰物 (ED) 是无处不在的化合物，能够干扰激素作用并影响人类健康。例如，暴露于 ED 会导致出生体重下降和代谢紊乱发生率增加。因此，IGF 系统是内分泌干扰的潜在靶标。本综述总结了关于暴露于主要类别的内分泌干扰物（二恶英和类二恶英化合物、多环芳烃、多溴联苯醚、邻苯二甲酸酯、全氟烷基物质和双酚 A）对 IGF 系统的影响的科学现状。介绍了来自实验模型（体外和体内）和流行病学研究的证据。此外，还讨论了可能的作用机制和对甲基化的影响。有大量证据支持二恶英和类二恶英化合物与 IGF 破坏之间的联系，但人类研究报告的结果存在差异。另一方面，尽管只有少数动物研究调查了邻苯二甲酸酯对 IGF 系统的影响，但在人类中更一致地报告了它们与 IGF 水平和甲基化状态呈负相关。对于多溴联苯醚、全氟烷基物质和双酚 A，证据仍然有限。尽管一些 ED 类别的研究缺乏将 ED 暴露与 IGF 水平变化联系起来的证据，并且需要进一步研究以提高重现性并确定 ED 对 IGF 系统构成的风险程度，但这显然是一个令人关注的领域。
