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Stress triggers a coordinated physiological response involving the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This dual activation ensures that the body is prepared for both immediate and prolonged stress management. The process begins with the perception of a stressor. This initial phase activates the SNS, leading to the rapid release of adrenaline (epinephrine) from the adrenal glands.
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Modeling pulsativity in the hypothalamic-pituitary-adrenal hormonal axis.

Alexander N Churilov1, John G Milton2

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|May 19, 2022
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A new mathematical model reveals pulsatile control in the hypothalamic-pituitary-adrenal (HPA) axis. This model explains biological rhythms and ultradian oscillations, suggesting pulse modulation principles are key to understanding the HPA axis.

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Area of Science:

  • Endocrinology
  • Mathematical Biology
  • Systems Biology

Background:

  • The hypothalamic-pituitary-adrenal (HPA) axis regulates stress response and exhibits complex biological rhythms.
  • Existing models often simplify or omit pulsatile dynamics and time delays inherent in hormonal signaling.

Purpose of the Study:

  • To develop a novel mathematical model for HPA axis biological rhythms.
  • To investigate the role of pulsatile adrenocorticotropin (ACTH) release and time delays in HPA axis function.

Main Methods:

  • A system of impulsive time-delay differential equations was formulated.
  • Numerical simulations were performed to analyze model responses to hypothalamic inputs.

Main Results:

  • The model accurately replicates HPA axis responses to circadian and periodic inputs, consistent with previous models.
  • Oscillatory phenomena were observed even with zero time delay, indicating pulsatility's primary role.
  • The model accounts for ultradian oscillations in the pituitary gland.

Conclusions:

  • Adrenal gland effects appear downstream of the pulsatility origin.
  • Pulse modulated control principles are crucial for understanding HPA axis dynamics.
  • The developed model offers new insights into the mechanisms governing biological rhythms within the HPA axis.