Gupta2007_HypothalamicPituitaryAdrenal_ModelB

ABSTRACT:

This a model from the article:
Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenalaxis model reveals bistability.
Gupta S, Aslakson E, Gurbaxani BM, Vernon SD. Theor Biol Med Model 2007 Feb 14;4:8 17300722 ,
Abstract:
BACKGROUND: The body's primary stress management system is the hypothalamicpituitary adrenal (HPA) axis. The HPA axis responds to physical and mentalchallenge to maintain homeostasis in part by controlling the body's cortisollevel. Dysregulation of the HPA axis is implicated in numerous stress-relateddiseases. RESULTS: We developed a structured model of the HPA axis that includesthe glucocorticoid receptor (GR). This model incorporates nonlinear kinetics ofpituitary GR synthesis. The nonlinear effect arises from the fact that GRhomodimerizes after cortisol activation and induces its own synthesis in thepituitary. This homodimerization makes possible two stable steady states (lowand high) and one unstable state of cortisol production resulting in bistabilityof the HPA axis. In this model, low GR concentration represents the normalsteady state, and high GR concentration represents a dysregulated steady state.A short stress in the normal steady state produces a small perturbation in theGR concentration that quickly returns to normal levels. Long, repeated stressproduces persistent and high GR concentration that does not return to baselineforcing the HPA axis to an alternate steady state. One consequence of increasedsteady state GR is reduced steady state cortisol, which has been observed insome stress related disorders such as Chronic Fatigue Syndrome (CFS).CONCLUSION: Inclusion of pituitary GR expression resulted in a biologicallyplausible model of HPA axis bistability and hypocortisolism. High GRconcentration enhanced cortisol negative feedback on the hypothalamus and forcedthe HPA axis into an alternative, low cortisol state. This model can be used toexplore mechanisms underlying disorders of the HPA axis.

This model was taken from the CellML repository and automatically converted to SBML.
The original model was: Gupta S, Aslakson E, Gurbaxani BM, Vernon SD. (2007) - version=1.0
The original CellML model was created by:
Catherine Lloyd
[e-mail]
The University of Auckland

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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

ORGANISM(S): Homo sapiens

SUBMITTER: Camille Laibe 

PROVIDER: MODEL1006230036 | biostudies-other |

SECONDARY ACCESSION(S): 17300722

REPOSITORIES: biostudies-other