Roblitz2013 - Menstrual Cycle following GnRH analogue administration

Model Identifier
BIOMD0000000494
Short description
Roblitz2013 - Menstrual Cycle following GnRH analogue administration

The model describes the menstrual cycle feedback mechanisms. GnRH, FSH, LH, E2, P4, inbibins A and B, and follicular development are modelled. The model predicts hormonal changes following GnRH analogue administration. Simulation results agree with measurements of hormone blood concentrations. The model gives insight into mechanisms underlying gonadotropin supression.

This model is described in the article:

Röblitz S, Stötzel C, Deuflhard P, Jones HM, Azulay DO, van der Graaf PH, Martin SW.
J. Theor. Biol. 2013 Mar; 321: 8-27

Abstract:

The paper presents a differential equation model for the feedback mechanisms between gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), development of follicles and corpus luteum, and the production of estradiol (E2), progesterone (P4), inhibin A (IhA), and inhibin B (IhB) during the female menstrual cycle. Compared to earlier human cycle models, there are three important differences: The model presented here (a) does not involve any delay equations, (b) is based on a deterministic modeling of the GnRH pulse pattern, and (c) contains less differential equations and less parameters. These differences allow for a faster simulation and parameter identification. The focus is on modeling GnRH-receptor binding, in particular, by inclusion of a pharmacokinetic/pharmacodynamic (PK/PD) model for a GnRH agonist, Nafarelin, and a GnRH antagonist, Cetrorelix, into the menstrual cycle model. The final mathematical model describes the hormone profiles (LH, FSH, P4, E2) throughout the menstrual cycle of 12 healthy women. It correctly predicts hormonal changes following single and multiple dose administration of Nafarelin or Cetrorelix at different stages in the cycle.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • A mathematical model of the human menstrual cycle for the administration of GnRH analogues. Click here to expand
  • Susanna Röblitz, Claudia Stötzel, Peter Deuflhard, Hannah M Jones, David-Olivier Azulay, Piet H van der Graaf, Steven W Martin
  • Journal of theoretical biology , 3/ 2013 , Volume 321 , pages: 8-27 , PubMed ID: 23206386
  • Computational Systems Biology Group, Zuse Institute Berlin (ZIB), Berlin, Germany. susanna.roeblitz@zib.de
  • The paper presents a differential equation model for the feedback mechanisms between gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), development of follicles and corpus luteum, and the production of estradiol (E2), progesterone (P4), inhibin A (IhA), and inhibin B (IhB) during the female menstrual cycle. Compared to earlier human cycle models, there are three important differences: The model presented here (a) does not involve any delay equations, (b) is based on a deterministic modeling of the GnRH pulse pattern, and (c) contains less differential equations and less parameters. These differences allow for a faster simulation and parameter identification. The focus is on modeling GnRH-receptor binding, in particular, by inclusion of a pharmacokinetic/pharmacodynamic (PK/PD) model for a GnRH agonist, Nafarelin, and a GnRH antagonist, Cetrorelix, into the menstrual cycle model. The final mathematical model describes the hormone profiles (LH, FSH, P4, E2) throughout the menstrual cycle of 12 healthy women. It correctly predicts hormonal changes following single and multiple dose administration of Nafarelin or Cetrorelix at different stages in the cycle.
Contributors
Submitter of the first revision: Susanna Röblitz
Submitter of this revision: Susanna Röblitz
Modeller: Susanna Röblitz

Metadata information

is (2 statements)
BioModels Database BIOMD0000000494
BioModels Database MODEL1311220000

isDescribedBy (1 statement)
PubMed 23206386

isVersionOf (2 statements)
hasProperty (2 statements)
Human Disease Ontology ovarian disease
Mathematical Modelling Ontology Ordinary differential equation model

hasTaxon (2 statements)
Experimental Factor Ontology female
Taxonomy Mammalia


Curation status
Curated


Original model(s)
gyncycle

Connected external resources

Name Description Size Actions

Model files

BIOMD0000000494_url.xml SBML L2V4 representation of Roblitz2013 - Menstrual Cycle following GnRH analogue administration 430.05 KB Preview | Download

Additional files

BIOMD0000000494-biopax2.owl Auto-generated BioPAX (Level 2) 96.89 KB Preview | Download
BIOMD0000000494-biopax3.owl Auto-generated BioPAX (Level 3) 161.30 KB Preview | Download
BIOMD0000000494.m Auto-generated Octave file 42.08 KB Preview | Download
BIOMD0000000494.pdf Auto-generated PDF file 673.28 KB Preview | Download
BIOMD0000000494.png Auto-generated Reaction graph (PNG) 1.93 MB Preview | Download
BIOMD0000000494.sci Auto-generated Scilab file 67.00 Bytes Preview | Download
BIOMD0000000494.svg Auto-generated Reaction graph (SVG) 224.03 KB Preview | Download
BIOMD0000000494.vcml Auto-generated VCML file 923.00 Bytes Preview | Download
BIOMD0000000494.xpp Auto-generated XPP file 37.47 KB Preview | Download
BIOMD0000000494_urn.xml Auto-generated SBML file with URNs 428.88 KB Preview | Download

  • Model originally submitted by : Susanna Röblitz
  • Submitted: Nov 22, 2013 10:19:06 AM
  • Last Modified: Oct 10, 2014 12:32:28 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Oct 10, 2014 12:32:28 PM
    • Submitted by: Susanna Röblitz
    • With comment: Current version of Roblitz2013 - Menstrual Cycle following GnRH analogue administration
  • Version: 1 public model Download this version
    • Submitted on: Nov 22, 2013 10:19:06 AM
    • Submitted by: Susanna Röblitz
    • With comment: Original import of NoName

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
FSH bld

Glycoprotein hormones alpha chain ; blood
4.1 dimensionless
FSH pit

hypophysis ; Glycoprotein hormones alpha chain
48627.2 dimensionless
InhA delay

Inhibin beta A chain
86.84 dimensionless
LH bld

blood ; Lutropin subunit beta
2.667 dimensionless
R FSH

Follicle-stimulating hormone receptor
6.341 dimensionless
R GnRH a

Gonadotropin-releasing hormone receptor
0.00928 dimensionless
R GnRH i

Gonadotropin-releasing hormone receptor
9.409E-4 dimensionless
sa78 degraded 1.0 dimensionless
Reactions
Reactions Rate Parameters
FSH_bld + R_FSH => FSH_R; FSH_bld, R_FSH default*p240/facFSH*FSH_bld*default*R_FSH*default/default facFSH = 1.0; p240 = 3.52890638983354
s38 => FSH_pit; InhA_delay, InhB, InhA_delay, InhB default*p21/(1+(InhA_delay*default/p22)^p24+(InhB*default/p23)^p25)*1/(1+(freq/p11)^p13)/default p24 = 5.0; p22 = 95.81; p21 = 22129.0495793807; freq = 3.17876449742659; p11 = 10.0; p13 = 3.0; p23 = 70.0; p25 = 2.0
InhA => InhA_delay; InhA default*p156*InhA*default/default p156 = 4.28718453552891
s93 => LH_bld; GnRH_R_a, LH_Pit, Ago_R_a, Ago_R_a, GnRH_R_a, LH_Pit default*facLH/p12*(p16+p5*((GnRH_R_a*default+Ago_R_a*default)/p8)^p9/(1+((GnRH_R_a*default+Ago_R_a*default)/p8)^p9))*LH_Pit*default/default p8 = 3.0E-4; p9 = 5.0; p12 = 5.0; p16 = 0.00476024700196886; p5 = 0.190415249686773; facLH = 1.0
R_FSH_des => R_FSH; R_FSH_des default*p242*R_FSH_des*default/default p242 = 61.0291748702345
R_GnRH_i => R_GnRH_a; R_GnRH_i default*p307*R_GnRH_i*default/default p307 = 32.2176481116879
GnRH + R_GnRH_a => GnRH_R_a; GnRH, R_GnRH_a default*p302*GnRH*default*R_GnRH_a*default/default p302 = 322.176481116879
GnRH_R_a => GnRH + R_GnRH_a; GnRH_R_a default*p303*GnRH_R_a*default/default p303 = 644.352962233757
R_GnRH_a => R_GnRH_i; R_GnRH_a default*p306*R_GnRH_a*default/default p306 = 3.22176481116878
P4 => sa78_degraded; P4 default*p155*P4*default/default p155 = 5.12958654018257
Curator's comment:
(added: 22 Nov 2013, 12:55:18, updated: 22 Nov 2013, 12:55:18)
The model reproduces figures 6-11, 13 and 15 from the reference publication. Here figure 7 has been reproduced. The model was simulation using Copasi v4.11 (Build 64) and the plots were generated using gnuplot.