ABSTRACT
Air pollution exposure is ranked as a leading environmental risk factor for not only cardiopulmonary diseases but also for systemic health ailments including diabetes, reproductive abnormalities, and neuropsychiatric disorders, likely mediated by central neural stress mechanisms. Current experimental evidence links many air pollution health outcomes with activation of neuroendocrine sympathetic-adrenal-medullary and hypothalamic–pituitary–adrenal (HPA) stress axes associated with resultant increases in adrenal-derived hormone levels acting as circulating mediators of multi-organ stress reactions. Epidemiological and experimental investigations also demonstrated sex-specific responses to air pollutant inhalation, which may be attributed to hormonal interactions within the stress and reproductive axes. Sex hormones (androgens and estrogens) interact with neuroendocrine functions to influence hypothalamic responses, subsequently augmenting stress-mediated metabolic and immune changes. These neurohormonal interactions may contribute to innate sex-specific responses to inhaled irritants, inducing differing individual susceptibility. The aim of this review was to: (1) examine neuroendocrine co-regulation of the HPA axis by gonadal hormones, (2) provide experimental evidence demonstrating sex-specific respiratory and systemic effects attributed to air pollutant inhalation exposure, and (3) postulate proposed mechanisms of stress and sex hormone interactions during air pollution-related stress.
Highlights
Air pollution exposure responses are co-regulated by stress and sex hormones
Hypothalamic and CNS stress reactions are sensitive to sex hormones
Estrogen and testosterone influence HPA axis induction and glucocorticoid dynamics
Neuroendocrine axes interactions mediate sex-specific air pollutant health effects
Acknowledgments
Authors thank Drs. M Ian Gilmour and Chris Lau of the US. EPA and Dr. Meghan Rebuli of the University of North Carolina at Chapel Hill for their critical review of this manuscript.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Abbreviations
ACTH, adrenocorticotrophic hormone; AdR, adrenergic receptor; AR, androgen receptor; BNST, bed nucleus of the stria terminalis; CNS, central nervous system; CRH, corticotrophin-releasing hormone; DHT, dihydrotestosterone; ER, estrogen receptor; GABA, gamma-aminobutyric acid; GDX, gonadectomy; GR, glucocorticoid receptor; HPA, hypothalamic-pituitary-adrenal; HPG, hypothalamic-pituitary-gonadal; HPT, hypothalamic-pituitary-thyroid; OVX, ovariectomy; O3, ozone; PM2.5, fine particulate matter; PVN, paraventricular nucleus
Author contributions
DIA and UPK: Conceptualization; Visualization; Writing – original draft; Writing – review and editing.
Data availability statement
No data was used for the research described in this article.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/10937404.2024.2383637