Modelling cholesterol effects on the dynamics of the hypothalamic–pituitary–adrenal (HPA) axis
Open accessAbstract
A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis with cholesterol as a dynamical variable was derived to investigate the effects of cholesterol, the primary precursor of all steroid hormones, on the ultradian and circadian HPA axis activity. To develop the model, the parameter space was systematically examined by stoichiometric network analysis to identify conditions for ultradian oscillations, determine conditions under which dynamic transitions, i.e. bifurcations occur and identify bifurcation types. The bifurcations were further characterized using numerical simulations. Model predictions agree well with empirical findings reported in the literature, indicating that cholesterol levels may critically affect the global dynamics of the HPA axis. The proposed model provides a base for better understanding of experimental observations, it may be used as a tool for designing experiments and offers useful insights into the characteristics of basic dynamic regulatory mechanisms that, when impaired, may lead to the development of some modern-lifestyle-associated diseases.
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Values of the rate constants of reaction steps (R2.2), (R4), (R5.2), (R5.3) and (R12), associated with AVP effects, were derived from (39, 54, 59, 60) unless otherwise specified.
“Values of the rate constants of reaction steps (R2.2), (R4), (R5.2), (R5.3) and (R12), associated with AVP effects were derived from (39, 54, 59, 60) unless otherwise specified.”
From Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis (2022) · cites this paper as [54]
Section 2.1 (page unavailable) gives rate constants for R4 and R12, and Computational Details (page unavailable) says the constants were taken from previous work whenever possible. The copy does not identify AVP-associated steps R2.2, R5.2, or R5.3, so it supports only part of the attributed list. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe response to perturbations is highly variable and depends strongly on the phase angle of the selected ultradian oscillation at which the first perturbation was applied; cortisol oscillation amplitude may decrease, increase or remain unaltered.
“Moreover, as expected from our previous experience (54, 62), perturbations caused a highly variable response depending on the phase angle of the selected ultradian oscillation at which the first perturbation was applied.”
From Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis (2022) · cites this paper as [54]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredWhen k2.2, k4 and initial AVP concentration are all zero (the initial model), cortisol oscillation amplitudes do not depend on k5.3.
“In the first case k2.2, k4 and initial concentration of AVP are all equal to zero. This corresponds to the initial model (54). Under these conditions, amplitudes do not depend on k5.3 and hence only one value of amplitude is given for each k2.1 value.”
From Influence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis (2022) · cites this paper as [54]
Section 2.2 describes a cholesterol-regulated HPA model with rate constants k1–k13, and Section 3.2 discusses cortisol oscillation amplitude in relation to cholesterol. Searches for the claimed k2.2, k5.3 and AVP conditions found no passage addressing whether amplitude is independent of k5.3. (LLM, conf=0.78)
Experimental — accuracy not yet measured
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Impaired cholesterol metabolism, neurons, and neuropsychiatric disorders
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Self-citationInfluence of arginine vasopressin on the ultradian dynamics of Hypothalamic-Pituitary-Adrenal axis
Stojiljković, A. S., Čupić, Ž., Maćešić, S., Ivanović-Šašić, A., & Kolar-Anić, L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.976323 · Cited by 9 · see citing works
“Stoichiometric model of HPA axis activity in humans developed in our earlier work (54) has been used as the basis to incorporate influence of arginine vasopressin (AVP) into the HPA mechanism described by the initial model.”
BackgroundMethodInfluentialSelf-citation
- Authors
- Marković, V. M., Čupić, Ž., Maćešić, S., Stanojević, A., Vukojević, V., & Kolar-Anić, L.
- Affiliations
- University of Belgrade (RS)
- Karolinska Institutet (SE)
- Corresponding author
- Marković, Vladimir M.
- Venue
- Mathematical Medicine and Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-10-20
- Volume
- 33
- Issue
- 1
- Pages
- 1-28
- ISSN
- 1477-8599 (ISSN-L)
- 1477-8602
- OpenAlex
- W2307321386
- Cited by
- 31
- References
- 74
- Citations by year
- 2025: 5 · 2023: 4 · 2022: 2 · 2021: 1 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 8
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Mathematical Medicine and Biology A Journal of the IMA (publishedVersion)
- PubMed (publishedVersion)
- CER (University of Belgrade, Institute of Chemistry, Technology and Metallurgy) (submittedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja (172015, 45001, grants 172015 and 45001, 172015 and 45001)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- hypothalamic-pituitary-adrenal axis, cholesterol, steroid hormones, ultradian oscillations, circadian rhythm, bifurcation, dynamical transition, stoichiometric network analysis, mathematical model
- MeSH terms
- Ultradian Rhythm, Cholesterol, Circadian Rhythm, Humans, Hypothalamo-Hypophyseal System, Models, Theoretical, Pituitary-Adrenal System
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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