Relationship between physical activity, serum cortisol levels, and NR3C1 gene methylation in public security professionals from Espírito Santo

Name: MARTA TOMÁS JONASSE LAMPIÃO NAMUANHO

Publication date: 24/07/2026

Examining board:

Namesort descending Role
ADRIANA MADEIRA ALVARES DA SILVA Presidente
JOSÉ CLÁUDIO CASALI DA ROCHA Examinador Externo
MARCO CESAR CUNEGUNDES GUIMARAES Examinador Interno

Summary: Physical activity has emerged as a promising strategy for preventing and improving
both metabolic and mental disorders. The NR3C1 gene encodes the glucocorticoid
receptor, which mediates the effects of cortisol on target cells and modulates the
consequences of stress response and other endocrine actions. However, the
epigenetic mechanisms linking exercise to hypothalamic-pituitary-adrenal (HPA) axis
regulation remain poorly understood. Thus, we assessed whether a relationship
between physical activity, serum cortisol levels, and NR3C1 gene methylation profile.
This is a cross-sectional study of 261 Brazilian public security officers. Epigenetic
analysis was performed through quantitative pyrosequencing of extracted DNA.
Physical activity levels were assessed using the International Physical Activity
Questionnaire (IPAQ). Multivariate Poisson regression revealed that a sedentary
lifestyle was significantly associated with hypermethylation at CpG site 43 (p<0,001).
Conversely, CpG site 46 showed a higher likelihood of methylation in physically
active individuals. The analysis also demonstrated that higher anxiety levels are
associated with a lower probability of being physically active. Additionally, physically
active participants had higher basal cortisol levels. These findings suggest that
physical activity is associated with site-specific modulation of NR3C1 methylation,
highlighting a complex molecular interface between lifestyle, HPA axis function, and
mental health resilience.

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