Stress (health) toxicology: Pollutant exposure and the hypothalamic-pituitary-adrenal (HPA) axis

The body's stress response is essential for adaptation to the demands of the environment. Chronic activation or dysregulation of stress responses is associated with many diseases including cardiovascular disease, type 2 diabetes, dementia, depression, chronic fatigue, immune disorders, and others. Accordingly, effects of pollutants on biological systems that regulate stress responses may be an important mechanism through which exposures could contribute to disease processes. The present chapter provides an overview of how stress responses are implicated in biological effects of pollutant exposures, with a focus on the role of the hypothalamic-pituitary-adrenal (HPA) axis, the main endocrine axis of the stress response that plays a critical role in regulating the activation and resolution of stress responses. Ways in which HPA axis responses can be involved in health effects of pollutant exposure - as a direct target (endocrine disruption), as a mediator (chronic activation and innate stress reactivity), and as an effect modifier (stress x pollutant interactions) – will be discussed.