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Modeling and Dynamic Investigation of Hypothalamic–Pituitary–Adrenal (HPA) Axis in Response to Stress

Afzali Pourfereydouni, Mohammad Mahdi | 2022

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 55644 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Vafa, Ehsan
  7. Abstract:
  8. The “hypothalamus-pituitary-adrenal” axis is one of the most important axes of the human body, and cortisol is one of its key products, which plays an essential role in the immune system, stress management, and many diseases. Appropriate modeling and simulation of this axis can help us to understand how the body reacts to stress and inflammation, to examine relevant diseases, and how drugs affect the body. In this study, by combining an axial model of the hypothalamic-pituitary-adrenal axis with a model of adrenal cells, a bi-level model including several time delays has been developed that can predict the effect of stress on this axis. Some parameters of the model have been modified through sensitivity analysis and optimization methods based on experimental data obtained from cortisol concentration of 17 healthy people given in the literature. The simulation results show that the bi-level model can predict the concentration of cortisol and ACTH with an acceptable accuracy relative to the experimental data. The model predicts that the circadian rhythm has a peak around 8 A.M. which is correspond to experimental observations, but the ultradian rhythm is not observed in the simulation results. Moreover, the model can predict the effect of specific stress at different times of the day on variation of the cortisol concentration. The simulation results show that the closer this stress is to the peak hour (around 8 A.M), the more impact it has on plasma cortisol concentration.
  9. Keywords:
  10. Dynamic Modeling ; Stress ; Anxiety ; Cortisol ; Hypothalamic-Pituitary-Adrenal Axis ; Adrenal Cells Model ; Sensitivity Analysis

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