Neuroendocrine contribution to sex-related variations in adverse air pollution health effects

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

KEYWORDS:

• Air pollution
• sex-specific responses
• hypothalamic-pituitary-adrenal axis
• neuroendocrine sympathetic-adrenal-medullary axis
• neuroendocrine regulation
• gonadal hormones

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; PM_2.5, 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

Additional information

Funding

This work was supported by the U.S. EPA Intramural Research funds. DIA was supported, in part, by an appointment to the Research Participation Program at the Center for Public Health and Environmental Assessment at the US. EPA, administered by the Oak Ridge Institute for Science and Education through an interagency agreement [DW-089-92525001] between the US. Department of Energy and U.S. EPA.