Perrett2014 - GnRH pulse, ERK activity

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MODEL1509050002
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Related Publication
  • Pulsatile hormonal signaling to extracellular signal-regulated kinase: exploring system sensitivity to gonadotropin-releasing hormone pulse frequency and width.
  • Perrett RM, Voliotis M, Armstrong SP, Fowkes RC, Pope GR, Tsaneva-Atanasova K, McArdle CA
  • The Journal of biological chemistry , 3/ 2014 , Volume 289 , pages: 7873-7883 , PubMed ID: 24482225
  • From the Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Bristol BS1 3NY, United Kingdom.
  • Gonadotropin-releasing hormone (GnRH) is secreted in brief pulses that stimulate synthesis and secretion of pituitary gonadotropin hormones and thereby mediate control of reproduction. It acts via G-protein-coupled receptors to stimulate effectors, including ERK. Information could be encoded in GnRH pulse frequency, width, amplitude, or other features of pulse shape, but the relative importance of these features is unknown. Here we examine this using automated fluorescence microscopy and mathematical modeling, focusing on ERK signaling. The simplest scenario is one in which the system is linear, and response dynamics are relatively fast (compared with the signal dynamics). In this case integrated system output (ERK activation or ERK-driven transcription) will be roughly proportional to integrated input, but we find that this is not the case. Notably, we find that relatively slow response kinetics lead to ERK activity beyond the GnRH pulse, and this reduces sensitivity to pulse width. More generally, we show that the slowing of response kinetics through the signaling cascade creates a system that is robust to pulse width. We, therefore, show how various levels of response kinetics synergize to dictate system sensitivity to different features of pulsatile hormone input. We reveal the mathematical and biochemical basis of a dynamic GnRH signaling system that is robust to changes in pulse amplitude and width but is sensitive to changes in receptor occupancy and frequency, precisely the features that are tightly regulated and exploited to exert physiological control in vivo.
Contributors
Submitter of the first revision: Margaritis Voliotis
Submitter of this revision: Margaritis Voliotis
Modellers: Margaritis Voliotis

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BioModels Database MODEL1509050002

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Mathematical Modelling Ontology Ordinary differential equation model

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Non-curated
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ordinary differential equation model
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  • Model originally submitted by : Margaritis Voliotis
  • Submitted: Sep 5, 2015 7:39:28 PM
  • Last Modified: Feb 10, 2016 1:32:10 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Feb 10, 2016 1:32:10 PM
    • Submitted by: Margaritis Voliotis
    • With comment: Current version of Perrett2014 - GnRH pulse, ERK activity
  • Version: 1 public model Download this version
    • Submitted on: Sep 5, 2015 7:39:28 PM
    • Submitted by: Margaritis Voliotis
    • With comment: Original import of Perret2014_GnRH_ERK

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