- Author:
- Catherine Lloyd <c.lloyd@auckland.ac.nz>
- Date:
- 2010-06-26 00:18:55+12:00
- Desc:
- Corrected Pubmed ID in the documentation.
- Permanent Source URI:
- https://models.cellml.org/workspace/schlosser_selgrade_2000/rawfile/2a7f741800b044310a28e83b4ece3480c8644afb/schlosser_selgrade_2000.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : schlosser_model_2000.xml
CREATED : 20th June 2007
LAST MODIFIED : 20th 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 Schlosser and Selgrade's 2000 mathematical model of gonadotropin regulation during the menstrual cycle in women.
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="schlosser_model_2000" name="schlosser_model_2000">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Modelling Gonadotropin Regulation during the Menstrual Cycle in Women</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>
This CellML model runs in OpenCell to recreate the pubslihed results. The model also runs in COR but due to the time unit being days the model is not ideal for simulation in COR (where the default unit of time is ms). The units have been checked and they are consistent. The LH system (eq 1a-1e) and the FSH system (eq 2a-2e) are both described in this CellML model. Parameter values have been taken from tables 1 and 2 in the original published paper. We were unable to represent the time delays in equations 1c and 2c.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Abstract: Increasing concerns that environmental contaminants may disrupt the endocrine system require development of mathematical tools to predict the potential for such compounds to significantly alter human endocrine function. The endocrine system is largely self-regulating, compensating for moderate changes in dietary phytoestrogens (e.g., in soy products) and normal variations in physiology. However, severe changes in dietary or oral exposures or in health status (e.g., anorexia) , can completely disrupt the menstrual cycle in women. Thus, risk assessment tools should account for normal regulation and its limits. We present a mathematical model for the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in women as a function of estrogen, progesterone, and inhibin blood levels. The model reproduces the time courses of LH and FSH during the menstrual cycle and correctly predicts observed effects of administered estrogen and progesterone on LH and FSH during clinical studies. The model should be useful for predicting effects of hormonally active substances, both in the pharmaceutical sciences and in toxicology and risk assessment.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="schlosser_2000.png"/>
</imageobject>
</mediaobject>
<caption>Schematic diagram of the mathematical model of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) synthesis and release. Solid arrows represent pathways of synthesis (syn), release into the blood (rel), and clearance from the blood (clear). Dashed arrows represent regulatory pathways, either positive (+) or negative (-), with feedback from estradiol (E2), progesterone (P4), and inhibin (Ih).</caption>
</informalfigure>
<para>
The original paper reference is cited below:
</para>
<para>
A model of gonadotropin regulation during the menstrual cycle in women: qualitative features Paul M. Schlosser and James F. Selgrade, 2000,
<emphasis>Environmental Health Perspectives</emphasis>, 108, 873-881. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11035997&query_hl=1&itool=pubmed_docsum">PubMed ID: 11035997</ulink>
</para>
</sect1>
</article>
</documentation>
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<unit units="day" exponent="-1"/>
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<units name="first_order_rate_constant">
<unit units="day" exponent="-1"/>
</units>
<component name="environment">
<variable units="day" public_interface="out" name="time"/>
</component>
<component cmeta:id="RP_LH" name="RP_LH">
<variable units="microg_day" public_interface="out" name="rel_LH_E2_P4_RP_LH"/>
<variable units="microg" name="RP_LH" initial_value="467.0"/>
<variable units="microg_day" name="syn_LH_E2_P4"/>
<variable units="microg_day" name="V0_LH" initial_value="1400.0"/>
<variable units="microg_day" name="V1_LH" initial_value="95900.0"/>
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<variable units="ng_L" name="Km_LH" initial_value="360.0"/>
<variable units="nmol_L" name="Ki_LHP" initial_value="26.0"/>
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<variable units="L_nmol" name="CLH_P" initial_value="0.024"/>
<variable units="L_ng" name="CLH_E" initial_value="0.008"/>
<variable units="ng_L" public_interface="in" name="E2"/>
<variable units="ng_L" public_interface="in" name="E2_dE"/>
<variable units="nmol_L" public_interface="in" name="P4"/>
<variable units="nmol_L" public_interface="in" name="P4_dP"/>
<variable units="day" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
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<diff/>
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</bvar>
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</apply>
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<ci> rel_LH_E2_P4_RP_LH </ci>
</apply>
</apply>
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<eq/>
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<apply>
<divide/>
<apply>
<plus/>
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<apply>
<divide/>
<apply>
<times/>
<ci> V1_LH </ci>
<apply>
<power/>
<ci> E2_dE </ci>
<ci> h </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<power/>
<ci> Km_LH </ci>
<ci> h </ci>
</apply>
<apply>
<power/>
<ci> E2_dE </ci>
<ci> h </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<divide/>
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<ci> Ki_LHP </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="rel_LH_E2_P4_RP_LH_calculation">
<eq/>
<ci> rel_LH_E2_P4_RP_LH </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> kLH_rel </ci>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<ci> CLH_P </ci>
<ci> P4 </ci>
</apply>
</apply>
<ci> RP_LH </ci>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<times/>
<ci> CLH_E </ci>
<ci> E2 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="LH" name="LH">
<variable units="microg_l" name="LH" initial_value="40.0"/>
<variable units="litre" name="v_dis" initial_value="2.5"/>
<variable units="microg_l_day" name="clear_LH"/>
<variable units="first_order_rate_constant" name="kLH_cl" initial_value="14.0"/>
<variable units="microg_day" public_interface="in" name="rel_LH_E2_P4_RP_LH"/>
<variable units="day" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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</bvar>
<ci> LH </ci>
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<minus/>
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<divide/>
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<ci> v_dis </ci>
</apply>
<ci> clear_LH </ci>
</apply>
</apply>
<apply id="clear_LH_calculation">
<eq/>
<ci> clear_LH </ci>
<apply>
<times/>
<ci> kLH_cl </ci>
<ci> LH </ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="RP_FSH" name="RP_FSH">
<variable units="microg_day" public_interface="out" name="rel_FSH_E2_P4_RP_FSH"/>
<variable units="microg" name="RP_FSH" initial_value="0.0"/>
<variable units="microg_day" name="syn_FSH_Ih"/>
<variable units="microg_day" name="V_FSH" initial_value="4400.0"/>
<variable units="U_L" name="Ki_FSH_Ih" initial_value="1176.5"/>
<variable units="first_order_rate_constant" name="kFSH_rel" initial_value="45.0"/>
<variable units="L_nmol" name="CFSH_P" initial_value="3.0"/>
<variable units="L_ng2" name="CFSH_E" initial_value="0.005"/>
<variable units="U_L" public_interface="in" name="Ih_dIh"/>
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<variable units="nmol_L" public_interface="in" name="P4"/>
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<ci> rel_FSH_E2_P4_RP_FSH </ci>
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</apply>
<apply id="syn_FSH_Ih_calculation">
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<ci> syn_FSH_Ih </ci>
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<ci> P4 </ci>
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</apply>
</apply>
</apply>
</apply>
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<variable units="microg_l" name="FSH" initial_value="150.0"/>
<variable units="litre" name="v_dis" initial_value="2.5"/>
<variable units="microg_l_day" name="clear_FSH"/>
<variable units="first_order_rate_constant" name="kFSH_cl" initial_value="8.21"/>
<variable units="microg_day" public_interface="in" name="rel_FSH_E2_P4_RP_FSH"/>
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<connection>
<map_components component_2="environment" component_1="LH"/>
<map_variables variable_2="time" variable_1="time"/>
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<map_components component_2="environment" component_1="RP_FSH"/>
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<map_variables variable_2="E2_dE" variable_1="E2_dE"/>
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<connection>
<map_components component_2="P4_dP" component_1="RP_LH"/>
<map_variables variable_2="P4_dP" variable_1="P4_dP"/>
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<connection>
<map_components component_2="RP_LH" component_1="LH"/>
<map_variables variable_2="rel_LH_E2_P4_RP_LH" variable_1="rel_LH_E2_P4_RP_LH"/>
</connection>
<connection>
<map_components component_2="E2" component_1="RP_FSH"/>
<map_variables variable_2="E2" variable_1="E2"/>
</connection>
<connection>
<map_components component_2="P4" component_1="RP_FSH"/>
<map_variables variable_2="P4" variable_1="P4"/>
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<connection>
<map_components component_2="Ih_dIh" component_1="RP_FSH"/>
<map_variables variable_2="Ih_dIh" variable_1="Ih_dIh"/>
</connection>
<connection>
<map_components component_2="RP_FSH" component_1="FSH"/>
<map_variables variable_2="rel_FSH_E2_P4_RP_FSH" variable_1="rel_FSH_E2_P4_RP_FSH"/>
</connection>
<rdf:RDF>
<rdf:Bag rdf:about="rdf:#0b6686e8-5ac8-44f2-9816-27fcf4e68165">
<rdf:li>endocrine</rdf:li>
<rdf:li>pituitary</rdf:li>
<rdf:li>hypothalamus</rdf:li>
<rdf:li>gonadotropin</rdf:li>
</rdf:Bag>
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<dc:title>
Schlosser and Selgrade's 2000 mathematical model of gonadotropin regulation during the menstrual cycle in women.
</dc:title>
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<dc:publisher>The University of Auckland, Auckland Bioengineering Institute</dc:publisher>
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<rdf:Description rdf:about="rdf:#917f21c2-1949-43a5-9ae6-78ff3977893e">
<dcterms:W3CDTF>2007-06-20T00:00:00+00:00</dcterms:W3CDTF>
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<dcterms:alternative>estradiol concentration at a time with a delay</dcterms:alternative>
<dc:title>E2_dE</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#edc00eb0-829e-44fb-acf3-b19425209572">
<dcterms:W3CDTF>2000-00-00 00:00</dcterms:W3CDTF>
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<rdf:Description rdf:about="rdf:#c0b0645f-c1dc-455d-884e-49d5b3ef237c">
<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="rdf:#a2d79fe0-89ea-4916-b548-302210c6ca5b">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#19e34591-e5a6-43ac-b207-2c1aa748a268">
<vCard:FN>Catherine Lloyd</vCard:FN>
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<bqs:subject_type>keyword</bqs:subject_type>
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<rdf:Description rdf:about="rdf:#a44517cc-ba86-42d3-b2e7-ea4295bf8836">
<dcterms:W3CDTF>2007-09-05T15:07:12+12:00</dcterms:W3CDTF>
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<rdf:Description rdf:about="rdf:#a000630e-c038-4f3f-8e9d-57c8fbeec9f2">
<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="#Ih">
<dcterms:alternative>inhibin</dcterms:alternative>
<dc:title>Ih</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#10cb8846-a0c7-4998-9d5a-a46e4b00a219">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>Auckland Bioengineering Institute</vCard:Orgunit>
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<rdf:Description rdf:about="rdf:#fed374f0-f025-461b-9be0-6487f5b0dce1">
<dc:creator rdf:resource="rdf:#19e34591-e5a6-43ac-b207-2c1aa748a268"/>
<rdf:value>This is the CellML description of Schlosser and Selgrade's 2000 mathematical model of gonadotropin regulation during the menstrual cycle in women.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#1f95c1f7-bdff-4de8-99d7-c5a33b4da5a3">
<vCard:Given>Paul</vCard:Given>
<vCard:Family>Schlosser</vCard:Family>
<vCard:Other>M</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#466b9645-3186-449c-af00-9573abcf9c34">
<vCard:ORG rdf:resource="rdf:#10cb8846-a0c7-4998-9d5a-a46e4b00a219"/>
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<vCard:N rdf:resource="rdf:#51395f54-d313-423a-889b-75499a8172b6"/>
</rdf:Description>
<rdf:Description rdf:about="#LH">
<dcterms:alternative>blood concentration of luteinizing hormone</dcterms:alternative>
<dc:title>LH</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#d71b2624-5216-45b6-9760-020044854e33">
<bqs:Pubmed_id>11035997</bqs:Pubmed_id>
<bqs:JournalArticle rdf:resource="rdf:#2d5edae1-9153-47cb-9c89-815d5cde54d5"/>
</rdf:Description>
<rdf:Description rdf:about="#P4_dP">
<dcterms:alternative>progesterone concentration at a time with a delay</dcterms:alternative>
<dc:title>P4_dP</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#Ih_dIh">
<dcterms:alternative>inhibin concentration at a time with a delay</dcterms:alternative>
<dc:title>Ih_dIh</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#FSH">
<dcterms:alternative>blood concentration of follicle-stimulating hormone</dcterms:alternative>
<dc:title>FSH</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#51395f54-d313-423a-889b-75499a8172b6">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="#E2">
<dcterms:alternative>estradiol</dcterms:alternative>
<dc:title>E2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#2d5edae1-9153-47cb-9c89-815d5cde54d5">
<dc:creator rdf:resource="rdf:#35c8354d-158b-4cbe-b878-e75c1d42c85f"/>
<dc:title>A model of gonadotropin regulation during the menstrual cycle in women: qualitative features</dc:title>
<bqs:volume>108</bqs:volume>
<bqs:first_page>873</bqs:first_page>
<bqs:Journal rdf:resource="rdf:#7844d7b4-ac0f-421c-ae2d-a13b9823af30"/>
<dcterms:issued rdf:resource="rdf:#edc00eb0-829e-44fb-acf3-b19425209572"/>
<bqs:last_page>881</bqs:last_page>
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<rdf:Description rdf:about="rdf:#9d221d5a-9c16-4657-81d8-c6cbcac61b51">
<dc:creator rdf:resource="rdf:#c0b0645f-c1dc-455d-884e-49d5b3ef237c"/>
<rdf:value>The units are consistent and the model runs in PCEnv to give the published results - one note: to recreate all the published results will require different variants of the model (or CellML1.1 to import different initial conditions and parameter values) because the conditions for each result were different.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e4f15ea8-d106-4661-8f41-6a682edaf58b">
<dcterms:modified rdf:resource="rdf:#a44517cc-ba86-42d3-b2e7-ea4295bf8836"/>
<rdf:value>I've run the model in COR and in the process corrected all the units such that they are now consistent. I also altered a couple of the equations - in this case CellML could handle the time delays because they were fixed - and the model now runs in PCEnv to give the published results.</rdf:value>
<cmeta:modifier rdf:resource="rdf:#b8d78f4e-21cc-47f8-a916-a567a6729f6b"/>
</rdf:Description>
<rdf:Description rdf:about="#RP_LH">
<dcterms:alternative>releasable pool of luteinizing hormone</dcterms:alternative>
<dc:title>RP_LH</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#7844d7b4-ac0f-421c-ae2d-a13b9823af30">
<dc:title>Environmental Health Perspectives</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#P4">
<dcterms:alternative>progesterone</dcterms:alternative>
<dc:title>P4</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#RP_FSH">
<dcterms:alternative>releasable pool of follicle-stimulating hormone</dcterms:alternative>
<dc:title>RP_FSH</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#7e606991-0fcd-40f9-9082-64640bc93a37">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#65e73e4c-3c94-44c4-9f23-8eef5a0c8cd7"/>
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<rdf:Description rdf:about="rdf:#65e73e4c-3c94-44c4-9f23-8eef5a0c8cd7">
<vCard:Given>James</vCard:Given>
<vCard:Family>Selgrade</vCard:Family>
<vCard:Other>F</vCard:Other>
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</rdf:RDF>
</model>
