MODEL1006230036
type: SBMLModel
modified:
  W3 CDTF: Fri Jun 25 13:42:46 BST 2010
parameter: 165483
parameter: 165464
units def: 379353
parameter: 165486
volume units: 290956
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
parameter: 165495
parameter: 165471
parameter: 165492
notes: This a model from the article: Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis 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 hypothalamic pituitary adrenal (HPA) axis. The HPA axis responds to physical and mental challenge to maintain homeostasis in part by controlling the body's cortisol level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases. RESULTS: We developed a structured model of the HPA axis that includes the glucocorticoid receptor (GR). This model incorporates nonlinear kinetics of pituitary GR synthesis. The nonlinear effect arises from the fact that GR homodimerizes after cortisol activation and induces its own synthesis in the pituitary. This homodimerization makes possible two stable steady states (low and high) and one unstable state of cortisol production resulting in bistability of the HPA axis. In this model, low GR concentration represents the normal steady state, and high GR concentration represents a dysregulated steady state. A short stress in the normal steady state produces a small perturbation in the GR concentration that quickly returns to normal levels. Long, repeated stress produces persistent and high GR concentration that does not return to baseline forcing the HPA axis to an alternate steady state. One consequence of increased steady state GR is reduced steady state cortisol, which has been observed in some stress related disorders such as Chronic Fatigue Syndrome (CFS). CONCLUSION: Inclusion of pituitary GR expression resulted in a biologically plausible model of HPA axis bistability and hypocortisolism. High GR concentration enhanced cortisol negative feedback on the hypothalamus and forced the HPA axis into an alternative, low cortisol state. This model can be used to explore mechanisms underlying disorders of the HPA axis…
area units: 291053
name: Gupta2007_HypothalamicPituitaryAdrenal_ModelB
rule: 165462
rule: 165455
parameter: 165489
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
units def: 379304
time units: 379353
parameter: 165474
is described by: http://identifiers.org/pubmed/17300722
substance units: 178797
rule: 165459
compartment: 165450
parameter: 165465
curated: false
parameter: 165480
rule: 165454
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
parameter: 165468
created:
  W3 CDTF: Fri Jun 25 13:42:46 BST 2010
units def: 379329
length unit: 076409
modified:
  W3 CDTF: Fri Jun 25 13:42:46 BST 2010
parameter: 165477
rule: 165456
modified:
  W3 CDTF: Fri Jun 25 13:42:46 BST 2010

165483
type: Parameter
constant: true
value: 1.0
name: kcd

165464
type: Parameter
constant: false
value: 0.6
name: c

379353
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unit: 379366
name: time

379366
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exponent: 1.0
scale: 0
multipler: 3600.0
kind: SECOND

165486
type: Parameter
constant: true
value: 10.0
name: kad

165495
type: Parameter
constant: true
value: 0.9
name: krd

165471
type: Parameter
constant: false
value: 0.01
name: r

165492
type: Parameter
constant: true
value: 0.05
name: kcr

165489
type: Parameter
constant: true
value: 0.001
name: k

379304
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name: hour

379316
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exponent: 1.0
scale: 0
multipler: 3600.0
kind: SECOND

165474
type: Parameter
constant: false
value: 0.055
name: o

165450
type: Compartment
constant: true
units: litre
size: 1.0
spatial dimensions: 3.0

165465
type: Parameter
constant: false
value: NaN
name: f

165480
type: Parameter
constant: true
value: 0.1
name: ki2

165468
type: Parameter
constant: false
value: 0.055
name: a

379329
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name: first_order_rate_constant

379341
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exponent: -1.0
scale: 0
multipler: 3600.0
kind: SECOND

165477
type: Parameter
constant: true
value: 0.1
name: ki1