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Modeling the hypothalamus–pituitary–adrenal system: homeostasis by interacting positive and negative feedback

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Abstract

The hypothalamus–pituitary–adrenal (HPA) system is closely related to stress and the restoration of homeostasis. This system is stimulated in the second half of the night, decreases its activity in the daytime, and reaches the homeostatic level during the late evening. In this paper, we derive and discuss a novel model for the HPA system. It is based on three simple rules that constitute a principle of homeostasis and include only the most substantive physiological elements. In contrast to other models, its main components include, apart from the conventional negative feedback ingredient, a positive feedback loop. To validate the model, we present a parameter estimation procedure that enables one to adapt the model to clinical observations. Using this methodology, we are able to show that the novel model is capable of simulating clinical trials. Furthermore, the stationary state of the system is investigated. We show that, under mild conditions, the system always has a well-defined set-point, which reflects the clinical situation to be modeled. Finally, the computed parameters may be interpreted from a physiological point of view, thereby leading to insights about diseases like depression, obesity, or diabetes.

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Acknowledgements

This work was supported by grants (Clinical Research Group KFO-126) from the German Research Foundation.

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Authors and Affiliations

  1. Department of Mathematics and Computer Science, Emory University, 400 Dowman Drive E429, Atlanta, GA, 30033, USA

    Matthias Conrad

  2. Medical Clinic 1, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany

    Christian Hubold & Achim Peters

  3. Institute of Mathematics, University of Lübeck, Wallstrasse 40, 23560, Lübeck, Germany

    Bernd Fischer

Authors
  1. Matthias Conrad
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  2. Christian Hubold
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  3. Bernd Fischer
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  4. Achim Peters
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Correspondence to Matthias Conrad.

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Conrad, M., Hubold, C., Fischer, B. et al. Modeling the hypothalamus–pituitary–adrenal system: homeostasis by interacting positive and negative feedback. J Biol Phys 35, 149–162 (2009). https://doi.org/10.1007/s10867-009-9134-3

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  • DOI: https://doi.org/10.1007/s10867-009-9134-3

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