Gupta, Shakti, Aslakson, Eric, Gurbaxani, Brian M et al. · Theoretical biology & medical modelling · 2007 · DOI
This study created a mathematical model of the body's stress-response system (the HPA axis) that helps explain why some people with chronic stress develop low cortisol levels. The model shows that when stress is repeated over a long time, the body can get 'stuck' in a low-cortisol state, similar to what happens in ME/CFS. The research suggests this happens because of how cortisol's receptor proteins build up and change how the stress system works.
This study offers a plausible biological mechanism for the HPA axis dysfunction and low cortisol observed in ME/CFS patients. Understanding how chronic stress can 'lock' the stress system into an abnormal state may guide development of new treatments. The model bridges the gap between observed HPA axis abnormalities in ME/CFS and the cellular processes that cause them.
This is a mathematical model and does not provide direct experimental evidence that this bistability mechanism actually occurs in ME/CFS patients. The study does not prove that low cortisol in ME/CFS is caused by this mechanism—it demonstrates one theoretically plausible pathway. Clinical validation through patient studies measuring GR expression and HPA axis dynamics would be needed to confirm the model's relevance.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Gupta, Shakti, Aslakson, Eric, Gurbaxani, Brian M, & Vernon, Suzanne D (2007). Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability.. Theoretical biology & medical modelling. https://doi.org/10.1186/1742-4682-4-8
BibTeX
@article{mecfsatlas-gupta-2007-inclusion-glucocorticoid,
author = {Gupta, Shakti and Aslakson, Eric and Gurbaxani, Brian M and Vernon, Suzanne D},
title = {Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability.},
journal = {Theoretical biology & medical modelling},
year = {2007},
doi = {10.1186/1742-4682-4-8},
note = {PubMed: 17300722},
url = {https://www.mecfsatlas.com/evidence/gupta-2007-inclusion-glucocorticoid},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/gupta-2007-inclusion-glucocorticoid
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