Location: Macgregor, Leng, 2005 @ 24e52a3f7eab / macgregor_leng_2005_variant01.cellml

Author:

pmr2.import <nobody@models.cellml.org>

Date:

2009-06-17 15:04:12+12:00

Desc:

committing version02 of macgregor_leng_2005

Permanent Source URI:

https://staging.physiomeproject.org/workspace/macgregor_leng_2005/rawfile/24e52a3f7eabf7bd727c15aba57e5c4102ef0968/macgregor_leng_2005_variant01.cellml

<?xml version='1.0' encoding='utf-8'?>
<!--  FILE :  macgregor_model_2005.xml

CREATED :  19th June 2007

LAST MODIFIED : 19th 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 MacGregor and Leng's 2005 mathematical model of hypothalamic control of growth hormone secretion.

CHANGES:  
  
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Modelling the Hypothalamic Control of Growth Hormone Secretion</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 particular CellML model describes the full (pituitary + hypothalamic) model of the published article.  The units have been checked and are consistent, and the model runs in PCEnv to replicate the published results (as shown in figure 12 of the paper).
          </para>
  </section>
  <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
In most mammals, including humans, growth hormone (GH) is secreted in a pulsatile pattern, which is regulated by two hypothalamic peptides; growth hormone-releasing hormone (GHRH) and somatostatin.  The former stimulates GH secretion while the latter inhibits it.  The activity of the hypothalamic neuroendocrine neurones is affected by feedback from GH and somatomedins, including activation of somatostatin release and possibly inhibition of GHRH release.  Furthermore, there is evidence that somatostatin neurones may inhibit the activity of GHRH neurones.
</para>

<para>
In their 2005 model, MacGregor and Lend use mathematical equations to describe these biological features and present a model of the hypothalamic network that controls GH secretion (see <xref linkend="fig_reaction_diagram"/> below).
</para>

<para>
The complete original paper reference is cited below:
</para>

<para>
<ulink url="http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2826.2005.01370.x">Modelling the hypothalamic control of growth hormone secretion</ulink>, D. J. MacGregor and G. Leng, 2005, <ulink url="http://www.blackwell-synergy.com/toc/jne/17/12">
            <emphasis>Journal of Neuroendocrinology</emphasis>
          </ulink>, volume 17, 788-803.  (<ulink url="http://www.blackwell-synergy.com/doi/full/10.1111/j.1365-2826.2005.01370.x">Full text (HTML)</ulink> and PDF versions of the article are available to subscribers on the <emphasis>Journal of Neuroendocrinology</emphasis> website.)  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=16280026&amp;query_hl=1&amp;itool=pubmed_docsum">PubMed ID: 16280026</ulink>
</para>

<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>model diagram</title>
    </objectinfo>
    <imagedata fileref="macgregor_2005.png"/>
  </imageobject>
</mediaobject>
<caption>A schematic diagram of the different components and connections in the growth hormone secretory system.  Somatostatin (SOS) inhibits the secretion of both growth hormone-releasing hormone (GHRH) and growth hormone (GH).  After a delay, GH feeds back to prime the pool of releasable somatostatin, resulting in the bulk release of somatostatin, which in turn allows further GHRH release and and another burst of GH.</caption>
</informalfigure>
</sect1>
</article>
</documentation> 



  
  
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    <variable units="dimensionless" name="delta_r" initial_value="0.2"/>
    
    <variable units="dimensionless" public_interface="in" name="f"/>
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    <variable units="dimensionless" public_interface="in" name="j1"/>
    <variable units="nanomolar" public_interface="in" name="r"/>
    <variable units="nanomolar" public_interface="in" name="c"/>
    <variable units="nanomolar" public_interface="in" name="s"/>
    <variable units="nanomolar" public_interface="in" name="se"/>
    <variable units="minute" public_interface="in" name="time"/> 
    
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            <ci>time</ci>
          </bvar> 
          <ci> h </ci> 
        </apply>
        <apply>
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          <ci> j1 </ci> 
          <apply>
            <minus/>
            <apply>
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              <apply>
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                <ci> k4 </ci>
                <apply>
                  <times/>
                  <ci> k5 </ci>
                  <apply>
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                    <cn cellml:units="dimensionless"> 1.0 </cn> 
                    <ci> phi_r_s </ci>
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                </apply>
              </apply>
              <apply>
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                <apply>
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                  <ci> r </ci>
                  <ci> c </ci>
                </apply>
                <ci> f </ci>
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            </apply>
            <apply>
              <times/>
              <ci> k8 </ci> 
              <ci> h </ci>
            </apply>
          </apply>
        </apply>  
      </apply> 
    
      <apply id="phi_r_s_calculation">
        <eq/>
        <ci> phi_r_s </ci>
        <apply>
          <divide/>
          <cn cellml:units="dimensionless"> 1.0 </cn> 
          <apply>
            <plus/>
            <cn cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <exp/>
              <apply>
                <divide/>
                <apply>
                  <minus/>
                  <apply>
                    <minus/>
                    <apply>
                      <log/>
		      <apply>
                        <times/>
                        <cn cellml:units="per_nanomolar"> 1.0 </cn>
                        <apply>
                          <plus/>
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                          <ci> se </ci>
		        </apply>
		      </apply>
                    </apply>
                    <ci> sr </ci>
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                </apply>
                <ci> delta_r </ci>
              </apply>
            </apply>
          </apply>  
        </apply>
      </apply>
    </math> 
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    <variable units="dimensionless" public_interface="out" name="g" initial_value="2.0"/> 
    
    <variable units="first_order_rate_constant" name="g1" initial_value="1.0"/>
    <variable units="dimensionless" name="gmax" initial_value="5.0"/>
    <variable units="per_nanomolar" name="g2" initial_value="0.008"/>
    <variable units="dimensionless" name="hact"/>
    <variable units="dimensionless" name="n2" initial_value="2.0"/>
    <variable units="dimensionless" name="theta_2" initial_value="30.0"/>
    
    <variable units="dimensionless" public_interface="in" name="h_delta"/>
    <variable units="flux" public_interface="in" name="Is"/>
    <variable units="dimensionless" public_interface="in" name="j1"/>
    <variable units="minute" public_interface="in" name="time"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
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        <apply>
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            <ci>time</ci>
          </bvar> 
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        <apply>
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            <ci> hact </ci>
            <apply>
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                <ci> g </ci>
              </apply>
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          </apply>
          <apply>
            <times/>
            <ci> g2 </ci>
            <ci> Is </ci>
            <ci> g </ci> 
          </apply>
        </apply>  
      </apply>
 
      <apply id="hact_calculation">
        <eq/>
        <ci> hact </ci>
        <apply>
          <divide/>
          <apply>
            <power/>
            <ci> h_delta </ci>
            <ci> n2 </ci>
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          <apply>
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            <apply>
              <power/>
              <ci> h_delta </ci>
              <ci> n2 </ci>
            </apply>
            <apply>
              <power/>
              <apply>
                <times/>
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                <ci> theta_2 </ci>
              </apply>
              <ci> n2 </ci>
            </apply>
          </apply>  
        </apply>
      </apply>
    </math> 
  </component>

  <component cmeta:id="hh" name="hh">
     
    <variable units="nanomolar" public_interface="out" name="hh" initial_value="0.0"/> 
    
    <variable units="flux" name="Ih" initial_value="50.0"/>
    
    <variable units="dimensionless" public_interface="in" name="j1"/>
    <variable units="first_order_rate_constant" public_interface="in" name="k8"/>
    <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> hh </ci> 
        </apply>
        <apply>
          <times/>
          <ci> j1 </ci> 
          <apply>
            <minus/>
            <ci> Ih </ci>
            <apply>
              <times/>
              <ci> k8 </ci>
              <ci> hh </ci>
            </apply>
          </apply>
        </apply>  
      </apply> 
    </math> 
  </component>
  
  <component name="model_parameters">
    <variable units="dimensionless" public_interface="out" name="h_delta"/>
    <variable units="dimensionless" public_interface="out" name="h_delta1"/>
    <variable units="dimensionless" public_interface="out" name="j1" initial_value="10"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k7" initial_value="5.0"/>
    <variable units="flux" public_interface="out" name="Is"/>
    <variable units="first_order_rate_constant" public_interface="out" name="k8" initial_value="0.07"/>
    <variable units="nanomolar" public_interface="out" name="c" initial_value="0.01"/>

    <variable units="per_nanomolar" name="delta" initial_value="60.0"/>
    <variable units="per_nanomolar" name="delta1" initial_value="15.0"/>
    
    <variable units="nanomolar" public_interface="in" name="h"/>
    <variable units="nanomolar" public_interface="in" name="hh"/>
    <variable units="minute" public_interface="in" name="time"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
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        <apply>
          <times/>
          <apply>
            <plus/> 
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            <ci> hh </ci>
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      </apply> 

      <apply>
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        <apply>
          <times/>
          <apply>
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            <ci> hh </ci>
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      <apply>
        <eq/>
        <ci> Is </ci>
        <piecewise>
          <piece>
            <cn cellml:units="flux"> 10.0 </cn>
            <apply>
              <and/>
              <apply>
                <gt/>
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                <cn cellml:units="minute"> 0.0 </cn>
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              <apply>
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                <ci> time </ci>
                <cn cellml:units="minute"> 90.0 </cn>
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          <piece>
            <cn cellml:units="flux"> 0.0 </cn>
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              <apply>
                <gt/>
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                <cn cellml:units="minute"> 90.0 </cn>
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              <apply>
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                <ci> time </ci>
                <cn cellml:units="minute"> 180.0 </cn>
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            <cn cellml:units="flux"> 10.0 </cn>
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              <apply>
                <gt/>
                <ci> time </ci>
                <cn cellml:units="minute"> 180.0 </cn>
              </apply>
              <apply>
                <leq/>
                <ci> time </ci>
                <cn cellml:units="minute"> 270.0 </cn>
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            <cn cellml:units="flux"> 0.0 </cn>
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              <apply>
                <gt/>
                <ci> time </ci>
                <cn cellml:units="minute"> 270.0 </cn>
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              <apply>
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                <ci> time </ci>
                <cn cellml:units="minute"> 360.0 </cn>
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    </math> 
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  <connection>
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  <connection>
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    <map_variables variable_2="time" variable_1="time"/>
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    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
    <map_components component_2="environment" component_1="f"/>
    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
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<rdf:RDF>
  <rdf:Bag rdf:about="rdf:#21108480-0177-4661-aa67-a32d8cc46324">
    <rdf:li>growth hormone</rdf:li>
    <rdf:li>hypothalamus</rdf:li>
    <rdf:li>somatostatin</rdf:li>
    <rdf:li>growth hormone releasing hormone</rdf:li>
  </rdf:Bag>
  <rdf:Seq rdf:about="rdf:#c9b84d74-3bc4-4c84-aa34-bf92fb3d6e2a">
    <rdf:li rdf:resource="rdf:#defe8854-2305-4768-abe1-366b4c1c1e41"/>
    <rdf:li rdf:resource="rdf:#5d83f7df-7c6e-43e0-84df-2cb20acf993b"/>
  </rdf:Seq>
  <rdf:Description rdf:about="rdf:#a1307b00-a49b-4b59-bd31-ff8cff4c7e15">
    <vCard:ORG rdf:resource="rdf:#4dc2f283-a7b9-413c-9822-c96c644a2874"/>
    <vCard:EMAIL rdf:resource="rdf:#0074e35a-7320-417c-8ffd-da04aa3f74ca"/>
    <vCard:N rdf:resource="rdf:#7973be78-1364-49f9-8098-5a9724200a00"/>
  </rdf:Description>
  <rdf:Description rdf:about="">
    <dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
    <cmeta:comment rdf:resource="rdf:#790fdbd3-9a41-4af0-bea7-89f7be75237c"/>
    <dcterms:created rdf:resource="rdf:#53397ee2-b1f5-417f-8d93-961225d7d1ad"/>
    <dc:creator rdf:resource="rdf:#a1307b00-a49b-4b59-bd31-ff8cff4c7e15"/>
    <cmeta:modification rdf:resource="rdf:#fb240565-8ff6-43f8-8a7a-1e56437f76fd"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#defe8854-2305-4768-abe1-366b4c1c1e41">
    <rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
    <vCard:N rdf:resource="rdf:#39694593-b277-45a7-b193-2a5668a1a2cb"/>
  </rdf:Description>
  <rdf:Description rdf:about="/hh">
    <dcterms:alternative>human growth hormone</dcterms:alternative>
    <dc:title>hh</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#4dc2f283-a7b9-413c-9822-c96c644a2874">
    <vCard:Orgname>The University of Auckland</vCard:Orgname>
    <vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#be2f82ba-dcbc-4733-94ee-0ecd2fddbdd5">
    <vCard:Given>Catherine</vCard:Given>
    <vCard:Family>Lloyd</vCard:Family>
    <vCard:Other>May</vCard:Other>
  </rdf:Description>
  <rdf:Description rdf:about="/se">
    <dcterms:alternative>exogenous somatostatin</dcterms:alternative>
    <dc:title>se</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#5d83f7df-7c6e-43e0-84df-2cb20acf993b">
    <rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
    <vCard:N rdf:resource="rdf:#f52889a3-8e66-4864-aef2-88c1f43b54e7"/>
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  <rdf:Description rdf:about="rdf:#fb240565-8ff6-43f8-8a7a-1e56437f76fd">
    <dcterms:modified rdf:resource="rdf:#97a1988a-9346-4cb6-8b05-c569e944e8fc"/>
    <rdf:value>I've checked the model in COR and have corrected all the units.  I've also added some piecewise equations to stimulate the model (as set out in the figure legends of the paper).</rdf:value>
    <cmeta:modifier rdf:resource="rdf:#738722ff-ed9d-472c-a085-f3433a6fb047"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#5cfc0d4a-77e7-4e58-ac08-ca282aab57db">
    <bqs:Pubmed_id>16280026</bqs:Pubmed_id>
    <bqs:JournalArticle rdf:resource="rdf:#9ae82fcb-97af-4380-a8a3-0d71d815b744"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#73ab6072-f902-4e94-8cc9-ae0e3dd3f257">
    <dcterms:W3CDTF>2005-00-00 00:00</dcterms:W3CDTF>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#53397ee2-b1f5-417f-8d93-961225d7d1ad">
    <dcterms:W3CDTF>2007-05-28T00:00:00+00:00</dcterms:W3CDTF>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#97a1988a-9346-4cb6-8b05-c569e944e8fc">
    <dcterms:W3CDTF>2007-09-04T15:52:40+12:00</dcterms:W3CDTF>
  </rdf:Description>
  <rdf:Description rdf:about="/f">
    <dcterms:alternative>density of free GHRH receptors</dcterms:alternative>
    <dc:title>f</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="/g">
    <dcterms:alternative>releasable store of somatostatin</dcterms:alternative>
    <dc:title>g</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="#macgregor_model_2005">
    <dc:title>
        MacGregor and Leng's 2005 mathematical model of hypothalamic control of growth hormone secretion.
      </dc:title>
    <cmeta:bio_entity>hypothalamus</cmeta:bio_entity>
    <cmeta:comment rdf:resource="rdf:#a8dfbb63-684f-4412-8aad-4afa2b5b47f7"/>
    <bqs:reference rdf:resource="rdf:#5cfc0d4a-77e7-4e58-ac08-ca282aab57db"/>
    <bqs:reference rdf:resource="rdf:#7b422dfe-2fa6-4552-81e9-1b7af3b5a536"/>
  </rdf:Description>
  <rdf:Description rdf:about="/h">
    <dcterms:alternative>GH</dcterms:alternative>
    <dcterms:alternative>growth hormone</dcterms:alternative>
    <dc:title>h</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="/r">
    <dcterms:alternative>GHRH</dcterms:alternative>
    <dcterms:alternative>growth hormone releasing hormone</dcterms:alternative>
    <dc:title>r</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="/s">
    <dcterms:alternative>endogenous somatostatin</dcterms:alternative>
    <dc:title>s</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#7973be78-1364-49f9-8098-5a9724200a00">
    <vCard:Given>Catherine</vCard:Given>
    <vCard:Family>Lloyd</vCard:Family>
    <vCard:Other>May</vCard:Other>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#26b2d58c-fe42-4106-9f62-9caec4ebd5de">
    <vCard:FN>Catherine Lloyd</vCard:FN>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#abd20f21-286b-40ad-9ab6-f9ac642238b6">
    <dc:title>Journal of Neuroendocrinology</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#790fdbd3-9a41-4af0-bea7-89f7be75237c">
    <dc:creator rdf:resource="rdf:#26b2d58c-fe42-4106-9f62-9caec4ebd5de"/>
    <rdf:value>The model now runs in PCEnv to replicate the published results (as shown in figure 12).  The only difference is my stimulus was hand written by a piecewise equation where as the model authors used some sort of a random pulse generator...  I probably need to make the piecewise equation carry on for longer to get this result.</rdf:value>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#9ae82fcb-97af-4380-a8a3-0d71d815b744">
    <dc:creator rdf:resource="rdf:#c9b84d74-3bc4-4c84-aa34-bf92fb3d6e2a"/>
    <dc:title>Modelling the hypothalamic control of growth hormone secretion.</dc:title>
    <bqs:volume>17</bqs:volume>
    <bqs:first_page>788</bqs:first_page>
    <bqs:Journal rdf:resource="rdf:#abd20f21-286b-40ad-9ab6-f9ac642238b6"/>
    <dcterms:issued rdf:resource="rdf:#73ab6072-f902-4e94-8cc9-ae0e3dd3f257"/>
    <bqs:last_page>803</bqs:last_page>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#0074e35a-7320-417c-8ffd-da04aa3f74ca">
    <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:#39694593-b277-45a7-b193-2a5668a1a2cb">
    <vCard:Given>D</vCard:Given>
    <vCard:Family>MacGregor</vCard:Family>
    <vCard:Other>J</vCard:Other>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#7b422dfe-2fa6-4552-81e9-1b7af3b5a536">
    <dc:subject rdf:resource="rdf:#5151e189-41bc-42ea-bcce-66b4ba368648"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#738722ff-ed9d-472c-a085-f3433a6fb047">
    <vCard:N rdf:resource="rdf:#be2f82ba-dcbc-4733-94ee-0ecd2fddbdd5"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#f0d77927-6fdc-4fb1-8d74-1a4fd5df0de0">
    <vCard:FN>Catherine Lloyd</vCard:FN>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#5151e189-41bc-42ea-bcce-66b4ba368648">
    <bqs:subject_type>keyword</bqs:subject_type>
    <rdf:value rdf:resource="rdf:#21108480-0177-4661-aa67-a32d8cc46324"/>
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  <rdf:Description rdf:about="rdf:#a8dfbb63-684f-4412-8aad-4afa2b5b47f7">
    <dc:creator rdf:resource="rdf:#f0d77927-6fdc-4fb1-8d74-1a4fd5df0de0"/>
    <rdf:value>This is the CellML description of MacGregor and Leng's 2005 mathematical model of hypothalamic control of growth hormone secretion.</rdf:value>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#f52889a3-8e66-4864-aef2-88c1f43b54e7">
    <vCard:Given>G</vCard:Given>
    <vCard:Family>Leng</vCard:Family>
  </rdf:Description>
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</model>