Modeling the hypothalamus–pituitary–adrenal system: homeostasis by interacting positive and negative feedback
Open accessAbstract
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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The five replicated models were all deterministic ordinary differential equation models that captured the interactions in the HPA axis and their evolution through time.
“They were all deterministic ordinary differential equation models that captured the interactions in the HPA axis and their evolution through time.”
From Modeling the hypothalamus-pituitary-adrenal axis: A review and extension (2015) · cites this paper as [30]
Section 2 (Model) presents a time-dependent system of ordinary differential equations for interacting HPA-axis components, supporting the description of this paper’s model. The paper does not identify five replicated models or establish that all five were deterministic ODE models. (LLM, conf=0.83)
Experimental — accuracy not yet measuredFive models from the literature met the criteria for replication.
“Five models from the literature fit these criteria (24–27, 30).”
From Modeling the hypothalamus-pituitary-adrenal axis: A review and extension (2015) · cites this paper as [30]
In model (30), the mathematical part showed that the model had a stable equilibrium.
“The mathematical part of the study showed that the model had a stable equilibrium.”
From Modeling the hypothalamus-pituitary-adrenal axis: A review and extension (2015) · cites this paper as [30]
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- Authors
- Conrad, M., Hubold, C., Fischer, B., & Peters, A.
- Affiliations
- Emory University (US)
- University of Lübeck (DE)
- Corresponding author
- Conrad, Matthias
- ORCID
- Peters, Achim
- Venue
- Journal of Biological Physics
- Published
- 2009-02-25
- Volume
- 35
- Issue
- 2
- Pages
- 149-162
- ISSN
- 0092-0606 (ISSN-L)
- 1573-0689
- PMC
- PMC2669119
- OpenAlex
- W2026824332
- Cited by
- 47
- References
- 33
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 4 · 2013: 3 · 2012: 3
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Biological Physics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (KFO 126)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- homeostasis, positive feedback, negative feedback, circadian rhythm, parameter estimation, stationary states, set point, stress response, depression, obesity, diabetes mellitus
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