<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : bingzheng_model_1990.xml
CREATED : 14th November 2007
LAST MODIFIED : 14th November 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 Bingzheng, Zhenye, and Liansong's 1990 mathematical model of the regulation system of the secretion of glucocorticoids.
CHANGES:
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="bingzheng_model_1990" name="bingzheng_model_1990">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A mathematical model of the regulation system of the secretion of glucocorticoids</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model is known to run in PCEnv and COR and can recreate the published results. ValidateCellML verifies this model as valid CellML, with fully consistent units.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
The hypothalamic pituitary adrenal (HPA) axis represents a neuroendocrine system which plays an essential role in maintaining body homeostasis in response to stress. These stresses can be physical (e.g. infection) or psychological (e.g. fear), and both activate the hypothalamus to secrete corticotropin releasing hormone (CRF or CRH). In turn, the presence of CRF in the circulation stimulates the pituitary to release adrenocorticotropic hormone (ACTH) into the blood, where it travels to the adrenal glands and induces the secretion of cortisol from the adrenal cortex. Cortisol has a negative feedback effect on the hypothalamus and pituitary such that the secretion of CRF and ACTH are inhibited.
</para>
<para>
Cortisol has a number of important cellular and physiological functions, including:
</para>
<itemizedlist>
<listitem>
<para>inflammation suppression;</para>
</listitem>
<listitem>
<para>hormone secretion inhibition; and</para>
</listitem>
<listitem>
<para>the induction of lymphocyte apoptosis.</para>
</listitem>
</itemizedlist>
<para>
This wide range of effects of cortisol require the feedback loops of the HPA axis to be tightly regulated, and HPA axis disregulation is known to be a feature of numerous stress-related diseases.
</para>
<para>
Research on the HPA axis function has been hampered by the complexity of its influence on numerous systems. To better understand the function of the HPA axis it has become the subject of several mathematical models, including the model described here in CellML which was published by Bingzheng <emphasis>et al.</emphasis> in 1990 (see the figure below). Model simulation data compared well with experimental results, but it was agreed that the model required some further refinement to perfectly recreate the physiological situation.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
A mathematical model of the regulation system of the secretion of glucocorticoids, Liu Bingzheng, Zhao Zhenye and Chen Liansong, 1990,
<emphasis>Journal of Biological Physics</emphasis>, volume 17, issue 4, 221-233.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="bingzheng_1990.png"/>
</imageobject>
</mediaobject>
<caption>The HPA axis model has three compartments, namely the hypothalamus, pituitary and adrenals. Neural signals trigger CRF secretion by the hypothalamus. In turn, this signals to the pituitary to release ACTH which stimulates the adrenal gland to release cortisol. Cortisol acts on the hypothalamus and the pituitary to have a negative feedback effect on the release of CRH and ACTH respectively.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<units name="ng_ml">
<unit units="gram" prefix="nano"/>
<unit units="litre" prefix="milli" exponent="-1"/>
</units>
<units name="pg_ml">
<unit units="gram" prefix="pico"/>
<unit units="litre" prefix="milli" exponent="-1"/>
</units>
<units name="microg_dl">
<unit units="gram" prefix="micro"/>
<unit units="litre" prefix="deci" exponent="-1"/>
</units>
<units name="dl_microg">
<unit units="litre" prefix="deci"/>
<unit units="gram" prefix="micro" exponent="-1"/>
</units>
<units name="minute">
<unit units="second" multiplier="60.0"/>
</units>
<units name="first_order_rate_constant">
<unit units="minute" exponent="-1"/>
</units>
<units name="ng_ml_min">
<unit units="gram" prefix="nano"/>
<unit units="litre" prefix="milli" exponent="-1"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="pg_ml_min">
<unit units="gram" prefix="pico"/>
<unit units="litre" prefix="milli" exponent="-1"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="microg_dl_min">
<unit units="gram" prefix="micro"/>
<unit units="litre" prefix="deci" exponent="-1"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="mg_min">
<unit units="gram" prefix="milli"/>
<unit units="minute" exponent="-1"/>
</units>
<component name="environment">
<variable units="minute" public_interface="out" name="time"/>
</component>
<component name="X1" cmeta:id="X1">
<variable units="ng_ml" public_interface="out" name="X1" initial_value="10.0"/>
<variable units="ng_ml_min" name="a0" initial_value="0.0014"/>
<variable units="ng_ml_min" name="a1" initial_value="0.000517"/>
<variable units="dl_microg" name="a2" initial_value="0.0164"/>
<variable units="first_order_rate_constant" name="b1" initial_value="0.0598"/>
<variable units="microg_dl" public_interface="in" name="X3"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> X1 </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci> a0 </ci>
<apply>
<divide/>
<ci> a1 </ci>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<ci> a2 </ci>
<ci> X3 </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> b1 </ci>
<ci> X1 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="X2" cmeta:id="X2">
<variable units="pg_ml" public_interface="out" name="X2" initial_value="0.0"/>
<variable units="pg_ml_min" name="a3" initial_value="1.38"/>
<variable units="first_order_rate_constant" name="a4" initial_value="0.60"/>
<variable units="dl_microg" name="a5" initial_value="0.00498"/>
<variable units="first_order_rate_constant" name="b2" initial_value="0.053"/>
<variable units="microg_dl" public_interface="in" name="X3"/>
<variable units="ng_ml" public_interface="in" name="X1"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> X2 </ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<plus/>
<ci> a3 </ci>
<apply>
<times/>
<ci> a4 </ci>
<ci> X1 </ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<ci> a5 </ci>
<ci> X3 </ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> b2 </ci>
<ci> X2 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="X3" cmeta:id="X3">
<variable units="microg_dl" public_interface="out" name="X3" initial_value="0.0"/>
<variable units="microg_dl_min" name="a6" initial_value="0.0084"/>
<variable units="first_order_rate_constant" name="a7" initial_value="0.0081"/>
<variable units="first_order_rate_constant" name="b3" initial_value="0.0138"/>
<variable units="pg_ml" public_interface="in" name="X2"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> X3 </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci> a6 </ci>
<apply>
<times/>
<ci> a7 </ci>
<ci> X2 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> b3 </ci>
<ci> X3 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_2="environment" component_1="X1"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="X2"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="X3"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="X3" component_1="X1"/>
<map_variables variable_2="X3" variable_1="X3"/>
</connection>
<connection>
<map_components component_2="X3" component_1="X2"/>
<map_variables variable_2="X3" variable_1="X3"/>
<map_variables variable_2="X2" variable_1="X2"/>
</connection>
<connection>
<map_components component_2="X1" component_1="X2"/>
<map_variables variable_2="X1" variable_1="X1"/>
</connection>
<rdf:RDF>
<rdf:Bag rdf:about="rdf:#f2a07289-844d-4e03-a27e-398644d7b2c3">
<rdf:li>glucocorticoids</rdf:li>
<rdf:li>hypothalamus</rdf:li>
<rdf:li>cortisol</rdf:li>
<rdf:li>HPA axis</rdf:li>
</rdf:Bag>
<rdf:Seq rdf:about="rdf:#4ef6010c-e033-46a4-8ea2-a0fd2c06cad2">
<rdf:li rdf:resource="rdf:#32be77e3-b43f-4638-afd6-62e3923751c9"/>
<rdf:li rdf:resource="rdf:#9367a72c-5eee-434b-8944-cde45b7cd3bc"/>
<rdf:li rdf:resource="rdf:#e782dfa7-c1e7-4d3c-af87-a5a6bb487a47"/>
</rdf:Seq>
<rdf:Description rdf:about="rdf:#5dc94767-01c2-4dc3-abcf-79f624c98fe8">
<dcterms:W3CDTF>2007-12-03T00:00:00+00:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b4a1ffae-56dc-460a-947d-b5024064035c">
<dcterms:W3CDTF>1990-12</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#6896c3a8-fe2f-427b-aab8-2b3c8bbc7ced">
<bqs:Pubmed_id/>
<bqs:JournalArticle rdf:resource="rdf:#6dc95e15-12df-40c6-bccc-0ffb9c3d100c"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e782dfa7-c1e7-4d3c-af87-a5a6bb487a47">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#5953a5b7-6c3c-44d7-86e9-f25c31878987"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#32be77e3-b43f-4638-afd6-62e3923751c9">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#f4c6ee28-3643-4b50-b9bb-b1d708297869"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b98133e9-61e8-461a-9de1-74ad9852f6cd">
<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="">
<dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
<cmeta:comment rdf:resource="rdf:#e02debfe-dea0-4ea6-a4bd-299191d995b0"/>
<dcterms:created rdf:resource="rdf:#5dc94767-01c2-4dc3-abcf-79f624c98fe8"/>
<dc:creator rdf:resource="rdf:#0a3aca01-928b-4ec8-9669-a3c14e897f5d"/>
<cmeta:modification rdf:resource="rdf:#ad0e2069-c072-44d5-8b39-83bd9b7e63f8"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#6dc95e15-12df-40c6-bccc-0ffb9c3d100c">
<dc:creator rdf:resource="rdf:#4ef6010c-e033-46a4-8ea2-a0fd2c06cad2"/>
<dc:title>A mathematical model of the regulation system of the secretion of glucocorticoids</dc:title>
<bqs:volume>17</bqs:volume>
<bqs:first_page>221</bqs:first_page>
<bqs:Journal rdf:resource="rdf:#c51ac172-4a47-4011-82f2-d95353aeed5f"/>
<dcterms:issued rdf:resource="rdf:#b4a1ffae-56dc-460a-947d-b5024064035c"/>
<bqs:last_page>233</bqs:last_page>
</rdf:Description>
<rdf:Description rdf:about="#bingzheng_model_1990">
<dc:title>
Bingzheng, Zhenye, and Liansong's 1990 mathematical model of the regulation system of the secretion of glucocorticoids.
</dc:title>
<cmeta:bio_entity>hypothalamic pituitary adrenal axis</cmeta:bio_entity>
<cmeta:comment rdf:resource="rdf:#4871e5a4-b927-413f-aad5-9d360bea9d2e"/>
<bqs:reference rdf:resource="rdf:#6896c3a8-fe2f-427b-aab8-2b3c8bbc7ced"/>
<bqs:reference rdf:resource="rdf:#e58f6838-5338-431f-99de-c919180ddadd"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e02debfe-dea0-4ea6-a4bd-299191d995b0">
<dc:creator rdf:resource="rdf:#b98133e9-61e8-461a-9de1-74ad9852f6cd"/>
<rdf:value>This CellML model is known to run in PCEnv and COR and can recreate the published results. The units have been checked and they are consistent.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#c51ac172-4a47-4011-82f2-d95353aeed5f">
<dc:title>Journal of Biological Physics</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#0a3aca01-928b-4ec8-9669-a3c14e897f5d">
<vCard:ORG rdf:resource="rdf:#6590990e-6809-48d0-bab8-1823ebe27749"/>
<vCard:EMAIL rdf:resource="rdf:#64a5ecda-fb53-42cf-b569-05941d0de689"/>
<vCard:N rdf:resource="rdf:#08383371-7817-47fe-ad86-f16e87328adc"/>
</rdf:Description>
<rdf:Description rdf:about="/X3">
<dcterms:alternative>cortisol</dcterms:alternative>
<dc:title>X3</dc:title>
</rdf:Description>
<rdf:Description rdf:about="/X2">
<dcterms:alternative>ACTH</dcterms:alternative>
<dcterms:alternative>adrenocorticotropic hormone</dcterms:alternative>
<dc:title>X2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="/X1">
<dcterms:alternative>CRH</dcterms:alternative>
<dcterms:alternative>corticotropin releasing hormone</dcterms:alternative>
<dc:title>X1</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#9367a72c-5eee-434b-8944-cde45b7cd3bc">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#bbbe1167-33f3-4939-ae1a-2ee2086c657d"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#5953a5b7-6c3c-44d7-86e9-f25c31878987">
<vCard:Given>Chen</vCard:Given>
<vCard:Family>Liansong</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="rdf:#64a5ecda-fb53-42cf-b569-05941d0de689">
<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
<rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#bbbe1167-33f3-4939-ae1a-2ee2086c657d">
<vCard:Given>Zhao</vCard:Given>
<vCard:Family>Zhenye</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e0c43325-87ae-49a4-983e-e8f1be1ac050">
<bqs:subject_type>keyword</bqs:subject_type>
<rdf:value rdf:resource="rdf:#f2a07289-844d-4e03-a27e-398644d7b2c3"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e58f6838-5338-431f-99de-c919180ddadd">
<dc:subject rdf:resource="rdf:#e0c43325-87ae-49a4-983e-e8f1be1ac050"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#08383371-7817-47fe-ad86-f16e87328adc">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#ad0e2069-c072-44d5-8b39-83bd9b7e63f8">
<dcterms:modified rdf:resource="rdf:#857e12b9-0a58-4f84-be63-63bd1aaea5f3"/>
<rdf:value>updated documentation: curation status, removed reference links</rdf:value>
<cmeta:modifier rdf:resource="rdf:#b894e6b9-5766-400d-ab84-5b14a35c6ee0"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#6590990e-6809-48d0-bab8-1823ebe27749">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="rdf:#857e12b9-0a58-4f84-be63-63bd1aaea5f3">
<dcterms:W3CDTF>2009-05-28T14:56:57+12:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b894e6b9-5766-400d-ab84-5b14a35c6ee0">
<vCard:N rdf:resource="rdf:#af4b0ec3-8580-4d6e-b5cb-6b0579e26a39"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#4871e5a4-b927-413f-aad5-9d360bea9d2e">
<dc:creator rdf:resource="rdf:#cf8804ae-a03f-4001-b1da-e5c1f9aa1275"/>
<rdf:value>This is the CellML description of Bingzheng, Zhenye, and Liansong's 1990 mathematical model of the regulation system of the secretion of glucocorticoids.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#cf8804ae-a03f-4001-b1da-e5c1f9aa1275">
<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="rdf:#f4c6ee28-3643-4b50-b9bb-b1d708297869">
<vCard:Given>Liu</vCard:Given>
<vCard:Family>Bingzheng</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="rdf:#af4b0ec3-8580-4d6e-b5cb-6b0579e26a39">
<vCard:Given>James</vCard:Given>
<vCard:Family>Lawson</vCard:Family>
<vCard:Other>Richard</vCard:Other>
</rdf:Description>
</rdf:RDF>
</model>
