- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2009-06-17 14:50:17+12:00
- Desc:
- committing version02 of kyrylov_severyanova_vieira_2005
- Permanent Source URI:
- https://models.cellml.org/workspace/kyrylov_severyanova_vieira_2005/rawfile/e01d27a75e48f40b21b2bd2225ebde977df1a28e/kyrylov_severyanova_vieira_2005.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : kyrylov_model_2005.xml
CREATED : 11th July 2007
LAST MODIFIED : 11th July 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 Kyrylov et al's 2005 mathematical model of oscillatory behaviour of the hypothalamic-pituitary-adrenal axis.
CHANGES:
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<article>
<articleinfo>
<title>Modeling robust oscillatory behavior 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 hypothalamus-pituitary-adrenal (HPA) axis forms part of the endocrine system and it plays an essential role in the coordination of physiological processes in mammals. As its name suggests it comprises three glands; the hypothalamus, anterior pituitary and adrenal cortex. These glands function together by synthesising and secreting, or sensing and responding to, hormones such as corticotropin-releasing hormone (CRH), corticotropin (ACTH), and cortisol. Typically CRH is produced and secreted by the hypothalamus, stimulating the synthesis and secretion of ACTH by the anterior pituitary, in turn activating the adrenal cortex to produce and release cortisol. Cortisol has a negative feedback effect on CRH and ACTH production by the hypothalamus and anterior pituitary respectively (see figure below). The free cortisol in the plasma is bound by two proteins; corticosteroid-binding globulin (CBG) and albumin.
</para>
<para>
The hypothalamus effectively acts as an interface between the central nervous system (CNS) and the endocrine system. CNS activity affects the diurnal and circadian patterns of the HPA axis, and under conditions of stress the CNS increases its stimulation of the hypothalamus leading to a higher concentration of CRH and subsequently, significantly increased production of cortisol.
</para>
<para>
In the paper described here, Kyrylov <emphasis>et al.</emphasis> present a mathematical model of the HPA axis. Five system state variables were used to represent the circulatory concentrations of CRH, ACTH, free cortisol, CBG-bound cortisol and albumin-bound cortisol. Their model is based on the mathematical model published by Liu <emphasis>et al.</emphasis> in 1999 (which has also been described in CellML and can be found in the model repository), and further builds on this model by stabilising it and making it more robust to perturbations in certain parameter values. In addition, this new version of the model provides circadian rhythms, stress responses, and the ability to modulate gland size parameters, while retaining simplicity, and physiological relevance in terms of the hormone concentrations.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="kyrylov_2005.png"/>
</imageobject>
</mediaobject>
<caption>Schematic diagram of the hypothalamus-pituitary-adrenal (HPA) axis. Stimulatory and inhibitory paths are indicated by the arrows and + or - signs respectively. CRH represents corticotropin-releasing hormone, ACTH is corticotropin, and CBG represents corticosteroid-binding globulin.</caption>
</informalfigure>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://ieeexplore.ieee.org/search/srchabstract.jsp?arnumber=1542449&isnumber=32944&punumber=10&k2dockey=1542449@ieeejrns&query=%28%28kyrylov%29%3Cin%3Emetadata%29&pos=0">Modeling robust oscillatory behavior of the hypothalamic-pituitary-adrenal axis</ulink>, Vadim Kyrylov, Liudmila A. Severyanova, and Amandio Vieira, 2005, <ulink url="http://www.ieee.org/portal/site/mainsite/menuitem.818c0c39e85ef176fb2275875bac26c8/index.jsp?&pName=corp_level1&path=pubs/transactions&file=tbe.xml&xsl=generic.xsl">
<emphasis>IEEE Transactions on Biomedical Engineering</emphasis>
</ulink>, 52, 1977-1983. (A <ulink url="http://ieeexplore.ieee.org/iel5/10/32944/01542449.pdf">PDF</ulink> version of the article is available to journal subscribers on the <emphasis>IEEE Transactions on Biomedical Engineering</emphasis> website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16366221&query_hl=1&itool=pubmed_docsum">PubMed ID: 16366221</ulink>
</para>
</sect1>
</article>
</documentation>
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<rdf:RDF>
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<rdf:li>cortisol</rdf:li>
<rdf:li>endocrine</rdf:li>
<rdf:li>adrenal cortex</rdf:li>
<rdf:li>HPA axis</rdf:li>
<rdf:li>hypothalamus</rdf:li>
<rdf:li>hpa axis</rdf:li>
<rdf:li>anterior pituitary</rdf:li>
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<rdf:Description rdf:about="">
<dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
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<dc:creator rdf:resource="rdf:#829d8353-ac36-4ea6-af6d-d6fb1552b02e"/>
<dc:title>Modeling robust oscillatory behavior of the hypothalamic-pituitary-adrenal axis</dc:title>
<bqs:volume>52</bqs:volume>
<bqs:first_page>1977</bqs:first_page>
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<bqs:last_page>1983</bqs:last_page>
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<dc:title>IEEE Transactions on Biomedical Engineering</dc:title>
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<vCard:Given>Liudmila</vCard:Given>
<vCard:Family>Severyanova</vCard:Family>
<vCard:Other>A</vCard:Other>
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<rdf:Description rdf:about="rdf:#8cf5dcef-003c-45f4-a95b-2df614bf5c19">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
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<rdf:Description rdf:about="rdf:#9f6597f4-ddf4-4fea-b8bb-3af715d46bb4">
<dcterms:W3CDTF>2007-07-11T00:00:00+00:00</dcterms:W3CDTF>
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<rdf:Description rdf:about="rdf:#1c65ddcf-ea9e-4c7b-8e52-5500eb2db2bf">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
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<vCard:FN>Catherine Lloyd</vCard:FN>
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<dc:creator rdf:resource="rdf:#6f6bf0cd-1d85-42f4-85dd-f5ccbdf0cc75"/>
<rdf:value>This version of the HPA axis model runs in PCEnv to recreate the results published in the paper.</rdf:value>
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<bqs:subject_type>keyword</bqs:subject_type>
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<rdf:value>One unit inconsistency was fixed, and initial values for the five main variables were added (taken from figure 3 of the published paper). </rdf:value>
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Kyrylov et al's 2005 mathematical model of oscillatory behaviour of the hypothalamic-pituitary-adrenal axis.
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