- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2007-06-27 20:10:20+12:00
- Desc:
- committing version01 of farhy_bowers_veldhuis_2007
- Permanent Source URI:
- https://models.cellml.org/workspace/farhy_bowers_veldhuis_2007/rawfile/a159334c32e14ee02f7d81ab62452961173eb2fc/farhy_bowers_veldhuis_2007_a.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : farhy_model_2007.xml
CREATED : 21st June 2007
LAST MODIFIED : 21st 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 Farhy et al.'s 2007 model-projected mechanistic bases for sex differences in growth hormone regulation in humans.
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="farhy_bowers_veldhuis_model_2007_version01" name="farhy_bowers_veldhuis_model_2007_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Modelling Growth Hormone Regulation in Humans</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>
Neuroendocrine systems usually communicate via intermittent (pulsatile) rather than continuous (steady state) signal exchange. Hormone pulses transmit information to target tissues, for example the secretion patterns of growth hormone (GH) influence body size, lipoprotein metabolism, and insulin sensitivity. Pulsatile hormone secretion is controlled by integrative feedback mechanisms. Focusing, in particular, on GH; its secretion is stimulated by GH-releasing hormone (GHRH), is enhanced by ghrelin (GHS), and is inhibited by somatostatin (SRIF). GH feeds back into this system by regulating each of the GHRH (inhibited), SRIF (stimulated), and GHS (repressed) receptors.
</para>
<para>
The considerable complexity of neuroendocrine systems has provided an incentive for researchers to try to capture their characteristics in mathematical models. In their 2007 model, Farhy, Bowers and Veldhuis aim to explain how GHRH, SRIF, GHS and GH interact to control GH dynamics (see <xref linkend="fig_reaction_diagram"/> below). Interestingly, there are sex-based differences in the pathophysiology of GH secretion: for example, the the GH pulse amplitude is two-fold greater in women than in men, while GH secretory patterns are more disorderly in women compared with in men. These sex-based differences are addressed by Farhy <emphasis>et al.</emphasis> and the two CellML models are specific to males (version 1) and females (version 1 variant 1).
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://ajpregu.physiology.org/cgi/content/abstract/292/4/R1577">Model-projected mechanistic bases for sex differences in growth hormone regulation in humans</ulink>, Leon S. Farhy, Cyril Y. Bowers and Johannes D. Veldhuis, 2006, <ulink url="http://ajpregu.physiology.org/">
<emphasis>American Journal of Physiology. Regulatory, Integrative and Comparative Physiology</emphasis>
</ulink>, volume 17, 788-803. (<ulink url="http://ajpregu.physiology.org/cgi/content/full/292/4/R1577">Full text (HTML)</ulink> and <ulink url="http://ajpregu.physiology.org/cgi/reprint/292/4/R1577">PDF</ulink> versions of the article are available to subscribers on the <emphasis>American Journal of Physiology. Regulatory, Integrative and Comparative Physiology</emphasis> website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17185408&query_hl=1&itool=pubmed_docsum">PubMed ID: 17185408</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="farhy_model_2007.gif"/>
</imageobject>
</mediaobject>
<caption>A schematic diagram of the primary interconnections assumed among growth hormone (GH), growth hormone releasing hormone (GHRH), somatostatin (SRIF) in the periventricular nucleus (SRIF PeV) and arcuate nucleus (SRIF ArC), growth hormone secretagogues (GHS) and GH feedback in the human. The small green arrows denote greater potency (P) or efficacy (E) in women compared with men.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">
<!--
The following RDF block contains metadata that applies to this document
as a whole, as indicated by the empty about attribute on the
<rdf:Description> element.
-->
<rdf:Description rdf:about="">
<!--
The Model Builder Metadata. The Dublin Core "creator" element is used
to indicate the person who translated the model into CellML.
-->
<dc:creator rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Lloyd</vCard:Family>
<vCard:Given>Catherine</vCard:Given>
<vCard:Other>May</vCard:Other>
</vCard:N>
<vCard:EMAIL rdf:parseType="Resource">
<rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
</vCard:EMAIL>
<vCard:ORG rdf:parseType="Resource">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
</vCard:ORG>
</dc:creator>
<!--
The Creation Date metadata. This is the date on which the model
was translated into CellML.
-->
<dcterms:created rdf:parseType="Resource">
<dcterms:W3CDTF>2007-06-21</dcterms:W3CDTF>
</dcterms:created>
<!--
The Modification History metadata. This lists the changes that have been
made to the document, who made the changes, and when they were made.
-->
<!-- The Publisher metadata. -->
<dc:publisher>
The University of Auckland, Bioengineering Institute
</dc:publisher>
</rdf:Description>
<!--
The following metadata refers to the model itself, as indicated by the
reference to the ID "farhy_model_2007", which is declared
on the <model> element.
-->
<rdf:Description rdf:about="#farhy_model_2007">
<!-- A human readable name for the model. -->
<dc:title>
Farhy et al.'s 2007 model-projected mechanistic bases for sex differences in growth hormone regulation in humans..
</dc:title>
<!-- A comment regarding the model. -->
<cmeta:comment rdf:parseType="Resource">
<rdf:value>
This is the CellML description of Farhy et al.'s 2007 model-projected mechanistic bases for sex differences in growth hormone regulation in humans.
</rdf:value>
<!-- The creator of the comment. -->
<dc:creator rdf:parseType="Resource">
<vCard:FN>Catherine Lloyd</vCard:FN>
</dc:creator>
</cmeta:comment>
<cmeta:bio_entity>hypothalamus</cmeta:bio_entity>
<!-- Keyword(s) -->
<bqs:reference rdf:parseType="Resource">
<dc:subject rdf:parseType="Resource">
<bqs:subject_type>keyword</bqs:subject_type>
<rdf:value>
<rdf:Bag>
<rdf:li>growth hormone</rdf:li>
<rdf:li>somatostatin</rdf:li>
<rdf:li>hypothalamus</rdf:li>
<rdf:li>growth hormone releasing hormone</rdf:li>
</rdf:Bag>
</rdf:value>
</dc:subject>
</bqs:reference>
<!--
The CellML Metadata Specification recommends that bibliographic metadata
is used to provide information about the original model reference. The
"identifier" attribute on the "BibliographicReference" class provides an
elegant way to identify a cited reference using a database identifier
such as Pubmed. All associated data such as author, journal title,
date, etc can be looked up on the database.
-->
<bqs:reference rdf:parseType="Resource">
<bqs:Pubmed_id>17185408</bqs:Pubmed_id>
<bqs:JournalArticle rdf:parseType="Resource">
<dc:creator>
<rdf:Seq>
<rdf:li rdf:parseType="Resource">
<bqs:Person rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Farhy</vCard:Family>
<vCard:Given>Leon</vCard:Given>
<vCard:Other>S</vCard:Other>
</vCard:N>
</bqs:Person>
</rdf:li>
<rdf:li rdf:parseType="Resource">
<bqs:Person rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Bowers</vCard:Family>
<vCard:Given>Cyril</vCard:Given>
<vCard:Other>Y</vCard:Other>
</vCard:N>
</bqs:Person>
</rdf:li>
<rdf:li rdf:parseType="Resource">
<bqs:Person rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Veldhuis</vCard:Family>
<vCard:Given>Johannes</vCard:Given>
<vCard:Other>D</vCard:Other>
</vCard:N>
</bqs:Person>
</rdf:li>
</rdf:Seq>
</dc:creator>
<dc:title>
Model-projected mechanistic bases for sex differences in growth hormone regulation in humans.
</dc:title>
<dcterms:issued rdf:parseType="Resource">
<dcterms:W3CDTF>2007-04</dcterms:W3CDTF>
</dcterms:issued>
<bqs:Journal rdf:parseType="Resource">
<dc:title>American Journal of Physiololgy. Regulatory, Integrative and Comparative Physiology</dc:title>
</bqs:Journal>
<bqs:volume>292</bqs:volume>
<bqs:first_page>R1577</bqs:first_page>
<bqs:last_page>R1593</bqs:last_page>
</bqs:JournalArticle>
</bqs:reference>
</rdf:Description>
</rdf:RDF>
<units name="ng_ml">
<unit prefix="nano" units="gram"/>
<unit prefix="milli" units="litre" exponent="-1"/>
</units>
<units name="pg_ml">
<unit prefix="pico" units="gram"/>
<unit prefix="milli" units="litre" exponent="-1"/>
</units>
<units name="ng_ml_hr">
<unit units="ng_ml"/>
<unit units="hour" exponent="-1"/>
</units>
<units name="pg_ml_hr">
<unit units="pg_ml"/>
<unit units="hour" exponent="-1"/>
</units>
<units name="hour">
<unit multiplier="3600.0" units="second"/>
</units>
<units name="first_order_rate_constant">
<unit units="hour" exponent="-1"/>
</units>
<component name="environment">
<variable name="time" public_interface="out" units="hour"/>
</component>
<component name="GH" cmeta:id="GH">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="GH">
<dc:title>GH</dc:title>
<dcterms:alternative>growth hormone</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="GH" public_interface="out" units="ng_ml"/>
<variable name="GHS" public_interface="out" initial_value="20.0" units="dimensionless"/>
<variable name="k1" initial_value="3.0" units="first_order_rate_constant"/>
<variable name="kr1" initial_value="600.0" units="ng_ml_hr"/>
<variable name="t1" initial_value="400.0" units="pg_ml"/>
<variable name="n1" initial_value="5.0" units="dimensionless"/>
<variable name="n2" initial_value="2.0" units="dimensionless"/>
<variable name="g0" initial_value="1.0" units="dimensionless"/>
<variable name="ng0" initial_value="2.9" units="dimensionless"/>
<variable name="tg0" initial_value="200.0" units="dimensionless"/>
<variable name="t2" initial_value="10.0" units="pg_ml"/>
<variable name="SRIF_PeV" public_interface="in" units="pg_ml"/>
<variable name="F1_GHS" public_interface="in" units="dimensionless"/>
<variable name="GHRH" public_interface="in" units="pg_ml"/>
<variable name="time" public_interface="in" units="hour"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply><eq/>
<apply><diff/>
<bvar><ci>time</ci></bvar>
<ci> GH </ci>
</apply>
<apply><plus/>
<apply><minus/>
<apply><times/>
<ci> k1 </ci>
<ci> GH </ci>
</apply>
<apply><times/>
<ci> kr1 </ci>
<apply><plus/>
<apply><divide/>
<apply><power/>
<apply><divide/>
<ci> GHRH </ci>
<ci> t1 </ci>
</apply>
<ci> n1 </ci>
</apply>
<apply><plus/>
<apply><power/>
<apply><divide/>
<ci> GHRH </ci>
<ci> t1 </ci>
</apply>
<ci> n1 </ci>
</apply>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
</apply>
<apply><times/>
<ci> g0 </ci>
<apply><divide/>
<apply><power/>
<apply><divide/>
<ci> GHS </ci>
<ci> tg0 </ci>
</apply>
<ci> ng0 </ci>
</apply>
<apply><plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply><power/>
<apply><divide/>
<ci> GHS </ci>
<ci> tg0 </ci>
</apply>
<ci> ng0 </ci>
</apply>
</apply>
</apply>
</apply>
<apply><divide/>
<apply><plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> F1_GHS </ci>
</apply>
<apply><plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply><power/>
<apply><divide/>
<ci> SRIF_PeV </ci>
<ci> t2 </ci>
</apply>
<ci> n2 </ci>
</apply>
<ci> F1_GHS </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="SRIF_PeV" cmeta:id="SRIF_PeV">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="SRIF_PeV">
<dc:title>SRIF_PeV</dc:title>
<dcterms:alternative>somatostatin in the periventricular nucleus</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="SRIF_PeV" public_interface="out" units="pg_ml"/>
<variable name="k4" initial_value="25.0" units="first_order_rate_constant"/>
<variable name="kr4" initial_value="20400.0" units="pg_ml_hr"/>
<variable name="t5" initial_value="10.0" units="ng_ml"/>
<variable name="n5" initial_value="2.0" units="dimensionless"/>
<variable name="D1" initial_value="0.82" units="hour"/>
<variable name="S_basal" initial_value="900.0" units="pg_ml_hr"/>
<variable name="GH" public_interface="in" units="ng_ml"/>
<variable name="time" public_interface="in" units="hour"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply><eq/>
<apply><diff/>
<bvar><ci>time</ci></bvar>
<ci> SRIF_PeV </ci>
</apply>
<apply><plus/>
<apply><minus/>
<apply><times/>
<ci> k4 </ci>
<ci> SRIF_PeV </ci>
</apply>
</apply>
<apply><times/>
<ci> kr4 </ci>
<apply><divide/>
<apply><power/>
<apply><divide/>
<apply><times/>
<ci> GH </ci>
<apply><minus/>
<ci> time </ci>
<ci> D1 </ci>
</apply>
</apply>
<ci> t5 </ci>
</apply>
<ci> n5 </ci>
</apply>
<apply><plus/>
<apply><power/>
<apply><divide/>
<apply><times/>
<ci> GH </ci>
<apply><minus/>
<ci> time </ci>
<ci> D1 </ci>
</apply>
</apply>
<ci> t5 </ci>
</apply>
<ci> n5 </ci>
</apply>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
</apply>
</apply>
<ci> S_basal </ci>
</apply>
</apply>
</math>
</component>
<component name="SRIF_ArC" cmeta:id="SRIF_ArC">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="SRIF_ArC">
<dc:title>SRIF_ArC</dc:title>
<dcterms:alternative>somatostatin in the arcuate nucleus</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="SRIF_ArC" public_interface="out" units="pg_ml"/>
<variable name="k2" initial_value="25.0" units="first_order_rate_constant"/>
<variable name="kr2" initial_value="2200.0" units="pg_ml_hr"/>
<variable name="t3" initial_value="400.0" units="pg_ml"/>
<variable name="n3" initial_value="2.0" units="dimensionless"/>
<variable name="D2" initial_value="0.2" units="hour"/>
<variable name="GHRH" public_interface="in" units="pg_ml"/>
<variable name="time" public_interface="in" units="hour"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply><eq/>
<apply><diff/>
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<ci> SRIF_ArC </ci>
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<ci> SRIF_ArC </ci>
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<apply><times/>
<ci> kr2 </ci>
<apply><divide/>
<apply><power/>
<apply><divide/>
<apply><times/>
<ci> GHRH </ci>
<apply><minus/>
<ci> time </ci>
<ci> D2 </ci>
</apply>
</apply>
<ci> t3 </ci>
</apply>
<ci> n3 </ci>
</apply>
<apply><plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply><power/>
<apply><divide/>
<apply><times/>
<ci> GHRH </ci>
<apply><minus/>
<ci> time </ci>
<ci> D2 </ci>
</apply>
</apply>
<ci> t3 </ci>
</apply>
<ci> n3 </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="GHRH" cmeta:id="GHRH">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="GHRH">
<dc:title>GHRH</dc:title>
<dcterms:alternative>growth hormone releasing hormone</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="GHRH" public_interface="out" units="pg_ml"/>
<variable name="k3" initial_value="40.0" units="first_order_rate_constant"/>
<variable name="kr3" initial_value="63000.0" units="pg_ml_hr"/>
<variable name="t4" initial_value="28.0" units="pg_ml"/>
<variable name="n4" initial_value="5.0" units="dimensionless"/>
<variable name="SRIF_PeV" public_interface="in" units="pg_ml"/>
<variable name="F2_GHS" public_interface="in" units="dimensionless"/>
<variable name="SRIF_ArC" public_interface="in" units="pg_ml"/>
<variable name="time" public_interface="in" units="hour"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply><eq/>
<apply><diff/>
<bvar><ci>time</ci></bvar>
<ci> GHRH </ci>
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<ci> k3 </ci>
<ci> GHRH </ci>
</apply>
<apply><times/>
<ci> kr3 </ci>
<apply><divide/>
<apply><plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> F2_GHS </ci>
</apply>
<apply><plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply><power/>
<apply><divide/>
<apply><plus/>
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<ci> SRIF_ArC </ci>
</apply>
<ci> t4 </ci>
</apply>
<ci> n4 </ci>
</apply>
<ci> F2_GHS </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="F">
<variable name="F1_GHS" public_interface="out" units="dimensionless"/>
<variable name="F2_GHS" public_interface="out" units="dimensionless"/>
<variable name="g1" initial_value="45000.0" units="dimensionless"/>
<variable name="g2" initial_value="100.0" units="dimensionless"/>
<variable name="tg1" initial_value="390.0" units="dimensionless"/>
<variable name="tg2" initial_value="10000.0" units="dimensionless"/>
<variable name="ng1" initial_value="3.0" units="dimensionless"/>
<variable name="ng2" initial_value="2.0" units="dimensionless"/>
<variable name="GHS" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<apply><times/>
<ci> g1 </ci>
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<apply><power/>
<apply><divide/>
<ci> GHS </ci>
<ci> tg1 </ci>
</apply>
<ci> ng1 </ci>
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<apply><plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply><power/>
<apply><divide/>
<ci> GHS </ci>
<ci> tg1 </ci>
</apply>
<ci> ng1 </ci>
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</apply>
</apply>
</apply>
</apply>
<apply><eq/>
<ci> F2_GHS </ci>
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<ci> g2 </ci>
<apply><divide/>
<apply><power/>
<apply><divide/>
<ci> GHS </ci>
<ci> tg2 </ci>
</apply>
<ci> ng2 </ci>
</apply>
<apply><plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply><power/>
<apply><divide/>
<ci> GHS </ci>
<ci> tg2 </ci>
</apply>
<ci> ng2 </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_1="GHRH" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="SRIF_PeV" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="SRIF_ArC" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="GH" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="GH" component_2="F"/>
<map_variables variable_1="F1_GHS" variable_2="F1_GHS"/>
<map_variables variable_1="GHS" variable_2="GHS"/>
</connection>
<connection>
<map_components component_1="GH" component_2="GHRH"/>
<map_variables variable_1="GHRH" variable_2="GHRH"/>
</connection>
<connection>
<map_components component_1="GH" component_2="SRIF_PeV"/>
<map_variables variable_1="SRIF_PeV" variable_2="SRIF_PeV"/>
<map_variables variable_1="GH" variable_2="GH"/>
</connection>
<connection>
<map_components component_1="GHRH" component_2="SRIF_PeV"/>
<map_variables variable_1="SRIF_PeV" variable_2="SRIF_PeV"/>
</connection>
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Farhy et al.'s 2007 model-projected mechanistic bases for sex differences in growth hormone regulation in humans..
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