A computer simulation of the hypothalamic-pituitary-adrenal axis
Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
Model Status
This model runs in OpenCell and COR. The units have been checked and they are consistent. Please note this CellML translation was based on a an online version of the original paper - a version which contains more defined parameter values than the paper linked to from PubMed (the more detailed description). Also there is a typo in this description in the ACTH Module. There should be a minus sign rather than a plus sign infront of (k4*[CRH]+k5) (We thank the original model author for highlighting this). The correct equation is as follows: d[ACTH]/dt = k4*[CRH]+k5 - k6*[ACTH]- (k4*[CRH]+k5)*Imax*[cortisol]/(Kd+[cortisol]). Unfortunately there are no published figures of the results of the original model so we cannot confirm the CellML translation recreates the original published results.
Model Structure
ABSTRACT: This paper describes the construction of a computer model that simulates the hypothalamic-pituitary-adrenal axis (HPA axis) regulation of cortisol production. It is presented to illustrate the process of physiological modeling using standard "off the shelf" technologies. The model simulates components of the HPA axis involved in the continuous secretion and elimination of cortisol, adrenocorticotropin (ACTH), and corticotropin releasing hormone (CRH). The physiological relations of these component pieces were modeled based on the current knowledge of their functioning. Rate constants, half lives, and receptor affinities were assigned values derived from the experimental literature. At its current level of development the model is able to accurately simulate the timing, magnitude and decay of the ACTH and cortisol concentration peaks resulting from the ovine-CRH stimulation test in normal and hypercortisolemic patients. The model will be used to predict the effects of lesions in different components of the HPA axis on the time course of cortisol and ACTH levels. We plan to use the model to explore the experimental conditions required to distinguish mechanisms underlying various disorders of the HPA axis, particularly depression. Efforts are currently underway to validate the model for a large variety of normal and pathological perturbations of the HPA axis.
The complete paper reference is cited below:
A computer simulation of the hypothalamic-pituitary-adrenal axis, J. Gonzalez-Heydrich, R.J. Steingard and I Kohane, 1994, Eighteenth Annual Proceedings of the Symposium for Computer Applications in Medical Care, pp1010. PubMed ID: 7949852
model diagram
Schematic diagram of the self-regulatory system for corticol secretion. CRH represents corticotropin-releasing hormone, and ACTH is adrenocorticotropic hormone.
$\frac{d \mathrm{cortisol}}{d \mathrm{time}}=\mathrm{k1}\mathrm{ACTH}+\mathrm{k2}-\mathrm{k3}\mathrm{cortisol}$
$\frac{d \mathrm{ACTH}}{d \mathrm{time}}=\mathrm{k4}\mathrm{CRH}+\mathrm{k5}-\mathrm{k6}\mathrm{ACTH}+(\mathrm{k4}\mathrm{CRH}+\mathrm{k5})\frac{\mathrm{Imax}\mathrm{cortisol}}{\mathrm{Kd}+\mathrm{cortisol}}$
$\frac{d \mathrm{CRH}}{d \mathrm{time}}=\mathrm{pulse}+\mathrm{k7}-\mathrm{k8}\mathrm{CRH}$
endocrine
hpa axis
HPA axis
cortisol
The University of Auckland, Auckland Bioengineering Institute
Catherine Lloyd
keyword
7949852
R
Steingard
J
J
Gonzalez-Heydrich
I
Kohane
The model has been checked in COR too. The units have been corrected and are consistent. The model runs in PCEnv but I'm not sure if it recreates the original results because the paper doesn't include any! Also, I think there may be a typo in the paper's equation to calculate ACTH - it looks a bit odd.
Catherine
Lloyd
May
The model has been checked in COR too. The units have been corrected and are consistent. The model runs in PCEnv but I'm not sure if it recreates the original results because the paper doesn't include any! Also, I think there may be a typo in the paper's equation to calculate ACTH - it looks a bit odd.
1994-00-00 00:00
Catherine
Lloyd
May
The University of Auckland
Auckland Bioengineering Institute
2007-09-02T16:04:16+12:00
Eighteenth Annual Proceedings of the Symposium for Computer Applications in Medical Care
2007-06-29T00:00:00+00:00
c.lloyd@auckland.ac.nz
A computer simulation of the hypothalamic-pituitary-adrenal axis
1010
Gonzalez-Heydrich et al.'s 1994 mathematical model of the HPA axis.
cortisol
corticotropin releasing hormone
CRH
Catherine Lloyd
acetylcholine
ACTH
This is the CellML description of Gonzalez-Heydrich et al.'s 1994 mathematical model of the HPA axis.