481039
constant: false
value: 0.6
name: c
type: Parameter

481056
constant: true
value: 0.9
name: krd
type: Parameter

MODEL1006230111
modified:
  W3 CDTF: Fri Jun 25 14:54:41 BST 2010
created:
  W3 CDTF: Fri Jun 25 14:54:41 BST 2010
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
parameter: 481040
rule: 481030
parameter: 481049
modified:
  W3 CDTF: Fri Jun 25 14:54:41 BST 2010
volume units: 290956
rule: 481034
units def: 702942
modified:
  W3 CDTF: Fri Jun 25 14:54:41 BST 2010
parameter: 481043
time units: 702966
parameter: 481056
parameter: 481039
units def: 702918
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…
parameter: 481053
parameter: 481046
rule: 481029
compartment: 481026
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
parameter: 481050
name: Gupta2007_HypothalamicPituitaryAdrenal_ModelA
type: SBMLModel
units def: 702966
parameter: 481055
parameter: 481052
parameter: 481045
is described by: http://identifiers.org/pubmed/17300722
substance units: 178797
parameter: 481042
area units: 237671
rule: 481037
curated: false
length unit: 821056
creator:
  ORG:
    orgname: University of Auckland
  n:
    given: Catherine
    family: Lloyd
rule: 481033

481046
constant: true
value: 0.1
name: ki1
type: Parameter

481042
constant: false
value: 0.055
name: a
type: Parameter

481052
constant: true
value: 10.0
name: kad
type: Parameter

481026
constant: true
units: litre
size: 1.0
spatial dimensions: 3.0
type: Compartment

702918
unit: 702930
name: hour
type: SBMLUnitsDef

481040
constant: false
value: NaN
name: f
type: Parameter

702978
exponent: 1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit

481050
constant: true
value: 1.0
name: kcd
type: Parameter

481049
constant: true
value: 0.1
name: ki2
type: Parameter

702954
exponent: -1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit

702966
unit: 702978
name: time
type: SBMLUnitsDef

481045
constant: false
value: 0.055
name: o
type: Parameter

481043
constant: false
value: 0.08
name: r
type: Parameter

702930
exponent: 1.0
scale: 0
multipler: 3600.0
kind: SECOND
type: SBMLUnit

481055
constant: true
value: 0.05
name: kcr
type: Parameter

702942
unit: 702954
name: first_order_rate_constant
type: SBMLUnitsDef

481053
constant: true
value: 0.001
name: k
type: Parameter