- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2007-09-02 03:11:28+12:00
- Desc:
- committing version02 of farhy_bowers_veldhuis_2007
- Permanent Source URI:
- https://models.cellml.org/workspace/farhy_bowers_veldhuis_2007/rawfile/291f585264e448638a61d37730da0fca017753c9/farhy_bowers_veldhuis_2007_b.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_model_2007" 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 intermitent (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 2) and females (version 2 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>
<para>
Please note this particular version of the model is specific to females and also GHRH alone is being injected. To simulate the injection of GHS and L-arginine the CellML model will have to be adapted slightly - this is relatively simple to do and will require changing a few initial conditions and parameters.
</para>
</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="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 units="second" multiplier="3600.0"/>
</units>
<units name="first_order_rate_constant">
<unit units="hour" exponent="-1"/>
</units>
<component name="environment">
<variable units="hour" public_interface="out" name="time"/>
</component>
<component name="GH" cmeta:id="GH">
<variable units="ng_ml" public_interface="out" name="GH" initial_value="0.0"/>
<variable units="dimensionless" public_interface="out" name="GHS" initial_value="20.0"/>
<variable units="first_order_rate_constant" name="k1" initial_value="3.0"/>
<variable units="ng_ml_hr" name="kr1" initial_value="600.0"/>
<variable units="pg_ml" name="t1" initial_value="357.0"/>
<variable units="dimensionless" name="n1" initial_value="5.0"/>
<variable units="dimensionless" name="n2" initial_value="2.0"/>
<variable units="dimensionless" name="g0" initial_value="2.0"/>
<variable units="dimensionless" name="ng0" initial_value="2.9"/>
<variable units="dimensionless" name="tg0" initial_value="200.0"/>
<variable units="pg_ml" name="t2" initial_value="10.0"/>
<variable units="pg_ml" public_interface="in" name="SRIF_PeV"/>
<variable units="dimensionless" public_interface="in" name="F1_GHS"/>
<variable units="pg_ml" public_interface="in" name="GHRH"/>
<variable units="pg_ml" public_interface="in" name="ghr_GHRH"/>
<variable units="hour" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="1">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> GH </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> kr1 </ci>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<power/>
<apply>
<divide/>
<apply>
<plus/>
<ci> GHRH </ci>
<ci> ghr_GHRH </ci>
</apply>
<ci> t1 </ci>
</apply>
<ci> n1 </ci>
</apply>
<apply>
<plus/>
<apply>
<power/>
<apply>
<divide/>
<apply>
<plus/>
<ci> GHRH </ci>
<ci> ghr_GHRH </ci>
</apply>
<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>
<times/>
<ci> k1 </ci>
<ci> GH </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="SRIF_PeV" cmeta:id="SRIF_PeV">
<variable units="pg_ml" public_interface="out" name="SRIF_PeV" initial_value="0.0"/>
<variable units="first_order_rate_constant" name="k4" initial_value="25.0"/>
<variable units="pg_ml_hr" name="kr4" initial_value="20400.0"/>
<variable units="ng_ml" name="t5" initial_value="10.0"/>
<variable units="dimensionless" name="n5" initial_value="2.0"/>
<variable units="pg_ml_hr" name="S_basal" initial_value="900.0"/>
<variable units="ng_ml" public_interface="in" name="GH"/>
<variable units="hour" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="2">
<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/>
<ci> GH </ci>
<ci> t5 </ci>
</apply>
<ci> n5 </ci>
</apply>
<apply>
<plus/>
<apply>
<power/>
<apply>
<divide/>
<ci> GH </ci>
<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">
<variable units="pg_ml" public_interface="out" name="SRIF_ArC" initial_value="0.0"/>
<variable units="first_order_rate_constant" name="k2" initial_value="25.0"/>
<variable units="pg_ml_hr" name="kr2" initial_value="2200.0"/>
<variable units="pg_ml" name="t3" initial_value="400.0"/>
<variable units="dimensionless" name="n3" initial_value="2.0"/>
<variable units="pg_ml" public_interface="in" name="GHRH"/>
<variable units="pg_ml" public_interface="in" name="ghr_GHRH"/>
<variable units="hour" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="3">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> SRIF_ArC </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> kr2 </ci>
<apply>
<divide/>
<apply>
<power/>
<apply>
<divide/>
<apply>
<plus/>
<ci> GHRH </ci>
<ci> ghr_GHRH </ci>
</apply>
<ci> t3 </ci>
</apply>
<ci> n3 </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<power/>
<apply>
<divide/>
<apply>
<plus/>
<ci> GHRH </ci>
<ci> ghr_GHRH </ci>
</apply>
<ci> t3 </ci>
</apply>
<ci> n3 </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> k2 </ci>
<ci> SRIF_ArC </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="GHRH" cmeta:id="GHRH">
<variable units="pg_ml" public_interface="out" name="GHRH" initial_value="0.0"/>
<variable units="first_order_rate_constant" name="k3" initial_value="40.0"/>
<variable units="pg_ml_hr" name="kr3" initial_value="63000.0"/>
<variable units="pg_ml" name="t4" initial_value="28.0"/>
<variable units="dimensionless" name="n4" initial_value="5.0"/>
<variable units="pg_ml" public_interface="in" name="SRIF_PeV"/>
<variable units="dimensionless" public_interface="in" name="F2_GHS"/>
<variable units="pg_ml" public_interface="in" name="SRIF_ArC"/>
<variable units="pg_ml" public_interface="in" name="ghr_GHRH"/>
<variable units="hour" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="4">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> GHRH </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<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/>
<ci> SRIF_PeV </ci>
<ci> SRIF_ArC </ci>
</apply>
<ci> t4 </ci>
</apply>
<ci> n4 </ci>
</apply>
<ci> F2_GHS </ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> ghr_GHRH </ci>
<cn cellml:units="first_order_rate_constant"> 1.0 </cn>
</apply>
</apply>
<apply>
<times/>
<ci> k3 </ci>
<ci> GHRH </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="F">
<variable units="dimensionless" public_interface="out" name="F1_GHS"/>
<variable units="dimensionless" public_interface="out" name="F2_GHS"/>
<variable units="dimensionless" name="g1" initial_value="90000.0"/>
<variable units="dimensionless" name="g2" initial_value="100.0"/>
<variable units="dimensionless" name="tg1" initial_value="390.0"/>
<variable units="dimensionless" name="tg2" initial_value="10000.0"/>
<variable units="dimensionless" name="ng1" initial_value="3.0"/>
<variable units="dimensionless" name="ng2" initial_value="2.0"/>
<variable units="dimensionless" public_interface="in" name="GHS"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="5">
<apply>
<eq/>
<ci> F1_GHS </ci>
<apply>
<times/>
<ci> g1 </ci>
<apply>
<divide/>
<apply>
<power/>
<apply>
<divide/>
<ci> GHS </ci>
<ci> tg1 </ci>
</apply>
<ci> ng1 </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<power/>
<apply>
<divide/>
<ci> GHS </ci>
<ci> tg1 </ci>
</apply>
<ci> ng1 </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci> F2_GHS </ci>
<apply>
<times/>
<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>
<component name="ghr_GHRH" cmeta:id="ghr_GHRH">
<variable units="pg_ml" public_interface="out" name="ghr_GHRH" initial_value="0.0"/>
<variable units="pg_ml_hr" public_interface="out" name="dghr_GHRH_dt"/>
<variable units="pg_ml_hr" name="inject"/>
<variable units="first_order_rate_constant" name="kghr" initial_value="15.0"/>
<variable units="pg_ml_hr" name="C" initial_value="10000.0"/>
<variable units="hour" name="onset" initial_value="2.0"/>
<variable units="hour" name="duration" initial_value="0.2"/>
<variable units="hour" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="6">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> ghr_GHRH </ci>
</apply>
<apply>
<minus/>
<ci> inject </ci>
<apply>
<times/>
<ci> kghr </ci>
<ci> ghr_GHRH </ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci> dghr_GHRH_dt </ci>
<apply>
<minus/>
<ci> inject </ci>
<apply>
<times/>
<ci> kghr </ci>
<ci> ghr_GHRH </ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci> inject </ci>
<piecewise>
<piece>
<cn cellml:units="pg_ml_hr"> 0.0 </cn>
<apply>
<lt/>
<ci> time </ci>
<ci> onset </ci>
</apply>
</piece>
<piece>
<ci> C </ci>
<apply>
<and/>
<apply>
<geq/>
<ci> time </ci>
<ci> onset </ci>
</apply>
<apply>
<leq/>
<ci> time </ci>
<apply>
<plus/>
<ci> onset </ci>
<ci> duration </ci>
</apply>
</apply>
</apply>
</piece>
<piece>
<cn cellml:units="pg_ml_hr"> 0.0 </cn>
<apply>
<gt/>
<ci> time </ci>
<apply>
<plus/>
<ci> onset </ci>
<ci> duration </ci>
</apply>
</apply>
</piece>
</piecewise>
</apply>
</math>
</component>
<connection>
<map_components component_2="environment" component_1="GHRH"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="SRIF_PeV"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="SRIF_ArC"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="GH"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ghr_GHRH"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="ghr_GHRH" component_1="GH"/>
<map_variables variable_2="ghr_GHRH" variable_1="ghr_GHRH"/>
</connection>
<connection>
<map_components component_2="F" component_1="GH"/>
<map_variables variable_2="F1_GHS" variable_1="F1_GHS"/>
<map_variables variable_2="GHS" variable_1="GHS"/>
</connection>
<connection>
<map_components component_2="GHRH" component_1="GH"/>
<map_variables variable_2="GHRH" variable_1="GHRH"/>
</connection>
<connection>
<map_components component_2="SRIF_PeV" component_1="GH"/>
<map_variables variable_2="SRIF_PeV" variable_1="SRIF_PeV"/>
<map_variables variable_2="GH" variable_1="GH"/>
</connection>
<connection>
<map_components component_2="SRIF_PeV" component_1="GHRH"/>
<map_variables variable_2="SRIF_PeV" variable_1="SRIF_PeV"/>
</connection>
<connection>
<map_components component_2="ghr_GHRH" component_1="SRIF_ArC"/>
<map_variables variable_2="ghr_GHRH" variable_1="ghr_GHRH"/>
</connection>
<connection>
<map_components component_2="SRIF_ArC" component_1="GHRH"/>
<map_variables variable_2="SRIF_ArC" variable_1="SRIF_ArC"/>
<map_variables variable_2="GHRH" variable_1="GHRH"/>
</connection>
<connection>
<map_components component_2="F" component_1="GHRH"/>
<map_variables variable_2="F2_GHS" variable_1="F2_GHS"/>
</connection>
<connection>
<map_components component_2="ghr_GHRH" component_1="GHRH"/>
<map_variables variable_2="ghr_GHRH" variable_1="ghr_GHRH"/>
</connection>
<rdf:RDF>
<rdf:Bag rdf:about="rdf:#00df554c-5782-4104-8b08-931a34989464">
<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:Seq rdf:about="rdf:#a4d9d35b-b0ed-4297-b2bb-f17a0b84478e">
<rdf:li rdf:resource="rdf:#152e09fe-95c7-48bd-aa77-598936a6a042"/>
<rdf:li rdf:resource="rdf:#96a5488e-b663-4683-a819-8cf3690c639e"/>
<rdf:li rdf:resource="rdf:#b61fd7f2-e3be-494a-b084-cd1778ca7310"/>
</rdf:Seq>
<rdf:Description rdf:about="rdf:#2a46a9bb-9af7-4d90-b1b5-5787eb1121e2">
<dc:title>American Journal of Physiololgy. Regulatory, Integrative and Comparative Physiology</dc:title>
</rdf:Description>
<rdf:Description rdf:about="">
<dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
<cmeta:comment rdf:resource="rdf:#4d9dfeb3-af37-4b2a-a950-69eb44ae7643"/>
<dcterms:created rdf:resource="rdf:#91323ee5-e3bf-41b6-8885-116ce2cb1c61"/>
<dc:creator rdf:resource="rdf:#41f015fb-6684-431c-b12a-dd26a3c09f5b"/>
<cmeta:modification rdf:resource="rdf:#24525ea7-0a57-4937-9dce-750885a1f3c1"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#61800b13-d2f2-42f1-875c-6162e71c20bd">
<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="rdf:#5b15644d-2a7a-471d-b6fc-2101ff6b5783">
<vCard:Given>Leon</vCard:Given>
<vCard:Family>Farhy</vCard:Family>
<vCard:Other>S</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#8547a838-a480-416b-b435-83b18c09ba77">
<dc:subject rdf:resource="rdf:#4fab8809-99ca-42fb-937f-0fe0fd98fbad"/>
</rdf:Description>
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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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