- Author:
- Tommy Yu <tommy.yu@auckland.ac.nz>
- Date:
- 2010-08-26 12:16:12+12:00
- Desc:
- xml:base fix
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/heinze_keener_midgley_1998/rawfile/08afec304029e86dadbd997ea533cf3017406e71/heinze_keener_midgley_1998_c.cellml
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A mathematical model of luteinizing hormone release from ovine pituitary cells in perifusion</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
The CellML model presented here represents the third model from the published paper which describes the basic dynamics of GnRH-receptor binding in the pituitary and the subsequent release of LH (as in the first core model) however in this third model the constant addition of LH to the releasable pool is removed such that it becomes exhaustable (as in the second model) and also the desensitised receptor is removed. The CellML model runs in COR and OpenCell to replicate the published results. The units have been checked and they are consistent.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: We model the effect of gonadotropin-releasing hormone (GnRH) on the production of luteinizing hormone (LH) by the ovine pituitary. GnRH, released by the hypothalamus, stimulates the secretion of LH from the pituitary. If stimulus pulses are regular, LH response will follow a similar pattern. However, during application of GnRH at high frequencies or concentrations or with continuous application, the pituitary delivers a decreased release of LH (termed desensitization). The proposed mathematical model consists of a system of nonlinear differential equations and incorporates two possible mechanisms to account for this observed behavior: desensitized receptor and limited, available LH. Desensitization was provoked experimentally in vitro by using ovine pituitary cells in a perifusion system. The model was fit to resulting experimental data by using maximum-likelihood estimation. Consideration of smaller models revealed that the desensitized receptor is significant. Limited, available LH was significant in three of four chambers. Throughout, the proposed model was in excellent agreement with experimental data.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="heinze_1998c.png"/>
</imageobject>
</mediaobject>
<caption>Schematic diagram of the components and reactions involved in the first model of luteinizing hormone (LH) release. kfb and kbf are kinetic constants, F and B represent the free and bound states of the gonadotropin-releasing hormone (GnRH) receptor, while R represents releasable LH and B is bound LH. s is the rate of the reaction, a1 determines the rate of basal LH secretion and a2 is the rate of LH secretion in the presence of bound receptor. There is no desensitised GnRH receptor in this model.</caption>
</informalfigure>
<para>
The original paper reference is cited below:
</para>
<para>
A mathematical model of luteinizing hormone release from ovine pituitary cells in perifusion, K. Heinze, R. W. Keener, and A. R. Midgley, Jr., 1998, <emphasis>American Journal of Physiology</emphasis>, 275, E1061-E1071. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/9843750">PubMed ID: 9843750</ulink></para>
</sect1>
</article>
</documentation>
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<unit units="ng"/>
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<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">GnRH</dc:title>
<dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">gonadotropin-releasing hormone</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
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<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">F</dc:title>
<dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">free gonadotropin-releasing hormone receptor</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
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<variable name="kbf" public_interface="in" units="first_order_rate_constant"/>
<variable name="B" public_interface="in" units="dimensionless"/>
<variable name="GnRH" public_interface="in" units="nanomolar"/>
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</bvar>
<ci> F </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> kbf </ci>
<ci> B </ci>
</apply>
<apply>
<times/>
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<ci> F </ci>
<ci> GnRH </ci>
</apply>
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</math>
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<dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">bound gonadotropin-releasing hormone receptor</dcterms:alternative>
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<variable name="F" public_interface="in" units="dimensionless"/>
<variable name="GnRH" public_interface="in" units="nanomolar"/>
<variable name="time" public_interface="in" units="hour"/>
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<ci>time</ci>
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<ci> B </ci>
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<apply>
<times/>
<ci> kfb </ci>
<ci> F </ci>
<ci> GnRH </ci>
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<times/>
<ci> kbf </ci>
<ci> B </ci>
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<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">R</dc:title>
<dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">releasable luteinizing hormone</dcterms:alternative>
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<ci> a2 </ci>
<ci> B </ci>
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<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">C</dc:title>
<dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">total (cumulative) amount of extracellular luteinizing hormone secreted</dcterms:alternative>
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<ci> a2 </ci>
<ci> B </ci>
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<ci> R </ci>
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</component>
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<variable initial_value="0.0328" name="a1" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.0830" name="a2" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="6.80" name="s" public_interface="out" units="first_order_rate_constant"/>
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<map_components component_1="C" component_2="environment"/>
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<connection>
<map_components component_1="F" component_2="GnRH"/>
<map_variables variable_1="GnRH" variable_2="GnRH"/>
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<map_components component_1="F" component_2="model_parameters"/>
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<map_components component_1="B" component_2="model_parameters"/>
<map_variables variable_1="kbf" variable_2="kbf"/>
<map_variables variable_1="kfb" variable_2="kfb"/>
</connection>
<connection>
<map_components component_1="B" component_2="GnRH"/>
<map_variables variable_1="GnRH" variable_2="GnRH"/>
</connection>
<connection>
<map_components component_1="R" component_2="B"/>
<map_variables variable_1="B" variable_2="B"/>
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<connection>
<map_components component_1="R" component_2="model_parameters"/>
<map_variables variable_1="s" variable_2="s"/>
<map_variables variable_1="a1" variable_2="a1"/>
<map_variables variable_1="a2" variable_2="a2"/>
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<map_variables variable_1="B" variable_2="B"/>
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<map_components component_1="C" component_2="R"/>
<map_variables variable_1="R" variable_2="R"/>
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<connection>
<map_components component_1="C" component_2="model_parameters"/>
<map_variables variable_1="a1" variable_2="a1"/>
<map_variables variable_1="a2" variable_2="a2"/>
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<rdf:Bag rdf:about="rdf:#d77800ad-4c88-4dff-aa59-916fe0bf4c39">
<rdf:li>luteinizing hormone</rdf:li>
<rdf:li>gonadotropin-releasing hormone</rdf:li>
<rdf:li>hypothalamus</rdf:li>
<rdf:li>pituitary</rdf:li>
</rdf:Bag>
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<rdf:li rdf:resource="rdf:#d14029b6-9df5-44ff-bb1a-47c69ae92ce5"/>
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Heinze et al's 1998 mathematical model of luteinizing hormone release from ovine pituitary cells in perifusion.
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