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March 26, 2026PLoS ONE1 citationsOpen Access

Subject-specific modeling of response to physical stress via hypothalamic-pituitary-adrenal and sympathoadrenal axes

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HHH. J. HarrisDCDavid M. ChanLFLaura Ellwein Fix

Key Result

A subject-specific mathematical model integrating the HPA and sympathoadrenal axes demonstrated qualitative agreement with cortisol and catecholamine dynamics under acute physical stress.

Key Points

  • The aim is to model the response of the HPA and SA axes to physical stress for improved understanding of hormonal dynamics.
  • Extended existing HPA axis model to include SA axis using differential equations.
  • Conducted sensitivity analysis through Morris screening to assess parameter influences.
  • Utilized constrained optimization to estimate model parameters based on time series data of cortisol and catecholamines.
  • Analyzed acute physical stress responses in a subject-specific manner.
  • The new model shows qualitative agreement with the observed cortisol and catecholamine data.
  • Integration of both HPA and SA axes enhances the accuracy of predicting stress hormone responses.

Structured PICO

I
Intervention
Mathematical modeling of the combined effects of the hypothalamic-pituitary-adrenal (HPA) and sympathoadrenal (SA) axes
O
Outcome
Qualitative agreement of the model with collected time series data of cortisol and catecholamine dynamics under acute physical stress

A novel mathematical model combining the HPA and SA axes successfully simulates cortisol and catecholamine dynamics in response to acute physical stress.

Abstract

The two main pathways for hormonal stress response are the hypothalamic-pituitary- adrenal (HPA) axis and the sympathoadrenal (SA) axis. The HPA axis produces and secretes cortisol, while the SA axis produces and secretes the fast-acting catecholamines, epinephrine and norepinephrine, which in turn stimulate cortisol. Since it is difficult to consistently measure or monitor their concentrations in plasma, mathematical modeling of the catecholamines and their connection to cortisol can provide more information about the acute stress response. Previous mathematical models have simulated the dynamics of the HPA axis, but a model of the SA axis has not been created nor one with the combined effects of the HPA and SA axes. We propose an extension of Bangsgaard and Ottesen’s differential equation-based HPA axis model that includes the SA axis 1. We performed sensitivity analysis using Morris screening and estimated model parameters using constrained optimization with respect to time series data of cortisol and catecholamine dynamics under acute physical stress. After subject-specific parameter estimation, the proposed model that includes both the HPA and SA axes shows qualitative agreement with the collected data.

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Cite This Study

Harris et al. (2026) studied this question. A subject-specific mathematical model integrating the HPA and sympathoadrenal axes demonstrated qualitative agreement with cortisol and catecholamine dynamics under acute physical stress.

synapsesocial.com/papers/69c4cc85fdc3bde448917cd6https://doi.org/10.1371/journal.pone.0344981
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