- Author:
- Hanne <Hanne@hanne-nielsens-macbook.local>
- Date:
- 2009-12-07 13:12:43+13:00
- Desc:
- Added images in ai and svg format, removed non pub med references
- Permanent Source URI:
- https://models.cellml.org/workspace/gupta_aslakson_gurbaxani_vernon_2007/rawfile/5910123c6c035710ead4a1ba84f4f692dfa5cff2/gupta_aslakson_gurbaxani_vernon_2007_b.cellml
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<!-- FILE : gupta_model_2007_version02.xml
CREATED : 1st June 2007
LAST MODIFIED : 1st 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 Gupta et al.'s 2007 hypothalamic pituitary adrenal axis model.
CHANGES:
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<title>A Hypothalamic Pituitary Adrenal Axis Model</title>
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<firstname>Catherine</firstname>
<surname>Lloyd</surname>
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<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
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<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
The hypothalamic pituitary adrenal (HPA) axis represents a neuroendocrine system which plays an essential role in maintaining body homeostasis in response to stress. These stresses can be physical (e.g. infection) or psychological (e.g. fear), and both activate the hypothalamus to secrete corticotropin releasing hormone (CRH). In turn, the presence of CRH in the circulation stimulates the pituitary to release adrenocorticotropic hormone (ACTH) into the blood, where it travels to the adrenal glands and induces the secretion of cortisol from the adrenal cortex. Cortisol has a negative feedback effect on the hypothalamus and pituitary such that the secretion of CRH and ACTH are inhibited.
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Cortisol has a number of important cellular and physiological functions, including:
</para>
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<para>inflammation suppression;</para>
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<para>hormone secretion inhibition; and</para>
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<para>the induction of lymphocyte apoptosis.</para>
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This wide range of effects of cortisol require the feedback loops of the HPA axis to be tightly regulated, and HPA axis disregulation is known to be a feature of numerous stress-related diseases.
</para>
<para>
Research on the HPA axis function has been hampered by the complexity of it's influence on numerous systems. To better understand the function of the HPA axis it has become the subject of several mathematical models, constructed from deterministic coupled ordinary differential equations. One such model by Gupta <emphasis>et al.</emphasis> (2007) uses non-linear kinetics to describe how CRH, ACTH and cortisol interact to regulate HPA axis function (see <xref linkend="fig_reaction_diagram"/> below). The model is unique in its inclusion of a glucocorticoid receptor (GR) in the pituitary, an inclusion which captures the biological reality of bistability in the HPA axis. This bistability arises from the homodimerisation of the GR after cortisol activation, which has a positive feedback on GR synthesis (again, please refer to <xref linkend="fig_reaction_diagram"/> below).
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<para>
The complete original paper reference is cited below:
</para>
<para>
Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability, Shakti Gupta, Eric Aslakson, Brian M. Gurbaxani and Suzanne D. Vernon, 2007, <emphasis>Theoretical Biology and Medical Modelling</emphasis>, volume 4, issue 8. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17300722&query_hl=1&itool=pubmed_docsum">PubMed ID: 17300722</ulink>
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<caption>The HPA axis model has three compartments, namely the hypothalamus, pituitary and adrenals. F is an external stress that triggers CRH (C) secretion by the hypothalamus. In turn, this signals to the pituitary to release ACTH (A) which stimulates the adrenal gland to release cortisol (O). Cortisol binds to the glucocorticoid receptor (R) in the pituitary and has a negative feedback effect on the release of CRH and ACTH. In addition, the cortisol-receptor complex has a positive feedback effect, promoting further receptor synthesis.</caption>
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Gupta et al's 2007 hypothalamic pituitary adrenal axis model.
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