The insulin-like growth factor system: A target for endocrine disruptors? A target for endocrine disruptors?

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.