- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2007-06-29 01:30:28+12:00
- Desc:
- committing version01 of gonzalezheydrich_steingard_kohane_1994
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/gonzalezheydrich_steingard_kohane_1994/rawfile/e5a24fee89bce031d6cbfea66dd0adf8da9a87a8/gonzalezheydrich_steingard_kohane_1994.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : gonzalezheydrich_model_1994.xml
CREATED : 28th June 2007
LAST MODIFIED : 28th June 2007
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.1 Specification.
DESCRIPTION : This file contains a CellML description of Gonzalez-Heydrich et al.'s 1994 mathematical model of the HPA axis.
CHANGES:
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A computer simulation of the hypothalamic-pituitary-adrenal axis</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
The hypothalamic-pituitary-adrenal axis (HPA axis) regulates the secretion of cortisol through a complex network of interacting components. Although our knowledge about each of these separate components is increasing, our understanding of how these components are combined into a network, and how this network functions, is still limited. In an attempt to address this issue, mathematical models of the HPA axis are being developed, and represent an informative, valuable, exploratory tool.
</para>
<para>
The current model described here in CellML is based on the HPA axis model published by Gonzalez-Heydrich <emphasis>et al.</emphasis> (1994) (the complete original paper reference is cited below). The mathematical model simulates components of the HPA axis involved in the continuous secretion and elimination of cortisol, adrenocorticotropin (ACTH), and corticotropin releasing hormone (CRH). The relationships between these components were modelled based on current knowledge of their functioning, and model parameters were derived from experimental results in the published literature. The presence of CRH and arginine-vasopressin (AVP), which are produced by the hypothalamus, stimulate the pituitary to secrete ACTH. In turn, ACTH triggers the release of cortisol from the adrenal gland. Cortisol has a direct negative feedback effect on the pituitary, and also on the hypothalamus, such that the secretion and synthesis of CRH, AVP and cortisol are inhibited.
</para>
<para>
A computer simulation of the hypothalamic-pituitary-adrenal axis, J. Gonzalez-Heydrich, R.J. Steingard and I Kohane, 1994, <emphasis>Eighteenth Annual Proceedings of the Symposium for Computer Applications in Medical Care</emphasis>, pp1010. (The Annual Symposium on Computer Applications in Medical Care currently does not have a website, but the text of this article can be found online <ulink url="http://www.chip.org/projects/hpa/paper-hpa.html">here</ulink>). <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=7949852&query_hl=1&itool=pubmed_docsum">PubMed ID: 7949852</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="gonzalezheidrich_1994.png"/>
</imageobject>
</mediaobject>
<caption>Schematic diagram of the self-regulatory system for corticol secretion. CRH represents corticotropin-releasing hormone, ACTH is adrenocorticotropic hormone, and F represents cortisol. The red lines represent positive feedback pathways, while the blue lines represent negative feedback loops.</caption>
</informalfigure>
<para>
Although this model is now more than 10 years old, it is still cited in the literature as one of the few mathematical models of the HPA axis which considers the dynamics of several hormones simultaneously, and doesn't focus solely on cortisol kinetics.
</para>
</sect1>
</article>
</documentation>
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<unit units="gram" prefix="micro"/>
<unit units="litre" prefix="milli" exponent="-1"/>
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<units name="minute">
<unit units="second" multiplier="60.0"/>
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<units name="flux">
<unit units="gram" prefix="micro"/>
<unit units="minute" exponent="-1"/>
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<component name="environment">
<variable units="minute" public_interface="out" name="time"/>
</component>
<component name="cortisol">
<variable units="mcg_ml" public_interface="out" name="cortisol"/>
<variable units="dimensionless" name="k1" initial_value="525.0"/>
<variable units="flux" name="k2" initial_value="0.01"/>
<variable units="dimensionless" name="k3" initial_value="0.01"/>
<variable units="mcg_ml" public_interface="in" name="ACTH"/>
<variable units="minute" public_interface="in" name="time"/>
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</bvar>
<ci> cortisol </ci>
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<ci> k1 </ci>
<ci> ACTH </ci>
</apply>
<ci> k2 </ci>
</apply>
<apply>
<times/>
<ci> k3 </ci>
<ci> cortisol </ci>
</apply>
</apply>
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</component>
<component name="ACTH" cmeta:id="ACTH">
<variable units="mcg_ml" public_interface="out" name="ACTH"/>
<variable units="dimensionless" name="k4" initial_value="10.0"/>
<variable units="flux" name="k5" initial_value="4E-3"/>
<variable units="dimensionless" name="k6" initial_value="0.035"/>
<variable units="mcg_ml" name="Kd" initial_value="0.004"/>
<variable units="dimensionless" name="Imax" initial_value="0.99"/>
<variable units="dimensionless" public_interface="in" name="CRH"/>
<variable units="dimensionless" public_interface="in" name="cortisol"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
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<bvar>
<ci>time</ci>
</bvar>
<ci> ACTH </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> k4 </ci>
<ci> CRH </ci>
</apply>
<ci> k5 </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k6 </ci>
<ci> ACTH </ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<ci> k4 </ci>
<ci> CRH </ci>
</apply>
<ci> k5 </ci>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci> Imax </ci>
<ci> cortisol </ci>
</apply>
<apply>
<plus/>
<ci> Kd </ci>
<ci> cortisol </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="CRH" cmeta:id="CRH">
<variable units="mcg_ml" public_interface="out" name="CRH"/>
<variable units="flux" name="k7" initial_value="1E-6"/>
<variable units="dimensionless" name="k8" initial_value="0.01"/>
<variable units="flux" name="pulse" initial_value="50.0"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
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<bvar>
<ci>time</ci>
</bvar>
<ci> CRH </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci> pulse </ci>
<ci> k7 </ci>
</apply>
<apply>
<times/>
<ci> k8 </ci>
<ci> CRH </ci>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_2="environment" component_1="cortisol"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ACTH"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="CRH"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="ACTH" component_1="cortisol"/>
<map_variables variable_2="cortisol" variable_1="cortisol"/>
<map_variables variable_2="ACTH" variable_1="ACTH"/>
</connection>
<connection>
<map_components component_2="ACTH" component_1="CRH"/>
<map_variables variable_2="CRH" variable_1="CRH"/>
</connection>
<rdf:RDF>
<rdf:Bag rdf:about="rdf:#54d87afa-2ccb-4546-bc19-72d0cace54b5">
<rdf:li>cortisol</rdf:li>
<rdf:li>HPA axis</rdf:li>
</rdf:Bag>
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<dcterms:W3CDTF>2007-06-29T00:00:00+00:00</dcterms:W3CDTF>
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<rdf:Description rdf:about="">
<dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
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<dcterms:W3CDTF>1994-00-00 00:00</dcterms:W3CDTF>
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<vCard:Given>Catherine</vCard:Given>
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<dc:title>
Gonzalez-Heydrich et al.'s 1994 mathematical model of the HPA axis.
</dc:title>
<cmeta:bio_entity>cortisol</cmeta:bio_entity>
<cmeta:comment rdf:resource="rdf:#ae0d60cd-686f-4e7e-afd0-7cc56a7f456d"/>
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<rdf:Description rdf:about="/ACTH">
<dcterms:alternative>acetylcholine</dcterms:alternative>
<dc:title>ACTH</dc:title>
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<vCard:FN/>
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<rdf:Description rdf:about="/CRH">
<dcterms:alternative>corticotropin releasing hormone</dcterms:alternative>
<dc:title>CRH</dc:title>
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<rdf:Description rdf:about="rdf:#2b55f524-5f4b-4890-9e41-31bdca33e533">
<dc:title>Eighteenth Annual Proceedings of the Symposium for Computer Applications in Medical Care</dc:title>
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<vCard:FN>Catherine Lloyd</vCard:FN>
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</model>
