Mathematical modelling of prolactin-receptor interaction and the corollary for prolactin receptor gene expression in skin
Catherine
Lloyd
Bioengineering Institute, University of Auckland
Model Status
This CellML version of the model has been checked in COR and PCEnv and the model runs to replicate the results in the original published paper. The units have been checked and are consistent. This particular variant of the model simulates a continuous infusion of prolactin over a nine day period.
Model Structure
When prolactin was first discovered it was identified exclusively as being a lactogenic hormone. However, since its initial discovery a wide range of biological functions have been assigned to prolactin, including water and electrolyte regulation, growth and development, metamorphosis, cell proliferation and differentiation, behaviour and immunoregulation. While the principal site of prolactin synthesis and secretion is the anterior pituitary gland, it is also produced locally by other tissues, including the skin.
Prolactin binds to a transmembrane cell surface receptor which exists as multiple isoforms, generated from a single gene by alternative splicing. These receptors are expressed throughout the body in many different tissues, consistent with prolactin's diverse range of physiological roles. Prolactin binds sequentially two two receptors, via two binding sites of differing affinities, to produce a dimer complex. This then initiates an intracellular signal transduction pathway, usually via a kinase cascade. While ligand-mediated receptor down-regulation has been observed (negative feedback), in certain tissues prolactin is also able to up-regulate expression of its own receptor (positive feedback). Signalling mechanisms within the cell can regulate receptor expression at the transcriptional level, and feedback can also occur on a larger spatial scale via different endocrine mechanisms. In combination, these mechanisms of prolactin receptor regulation may be an important determinant of the nature of the responses of a target tissue to prolactin.
In the paper described here, Soboleva et al. present a mathematical model of the prolactin-prolactin receptor signalling pathway (see figure below). Model simulations demonstrate that while prolactin receptor expression is insensitive to subcutaneous injections of prolactin, it does however respond to a prolonged infusion of prolactin. Under these latter conditions there is an initial acute period of receptor down-regulation followed by a prolonged period of up-regulation.
model diagram
Schematic diagram of the reactions described by the prolactin-prolactin receptor signalling pathway model. U represents the unbound prolactin receptor on the surface of the cell, B1 is the bound receptor, B2 is the dimerised receptor, P represents prolactin in the plasma, and R is the mRNA for the prolactin receptor.
The complete original paper reference is cited below:
Mathematical modelling of prolactin-receptor interaction and the corollary for prolactin receptor gene expression in skin, T.K. Soboleva, I. Vetharaniam, A.J. Nixon, R. Montenegro, A.J. Pearson and J. Sneyd, 2005,
Journal of Theoretical Biology
, 234, 289-298. (Full text and PDF versions of the article is available to journal subscribers on the Journal of Theoretical Biology website.) PubMed ID: 15757685
R
PRLR mRNA
U
concentration of unbound prolactin receptors on the surface of a cell
B1
concentration of prolactin bound to one receptor at binding site 1
B2
concentration of prolactin bound to two receptors (dimer)
P
concentration of plasma prolactin
prolactin
prolactin receptor
skin
gene expression
The University of Auckland, Bioengineering Institute
Soboleva et al.'s 2005 mathematical model of prolactin-receptor interaction and the corollary for prolactin receptor gene expression in skin.
J
Sneyd
T
Soboleva
K
A
Pearson
J
keyword
A
Nixon
J
R
Montenegro
15757685
Catherine
Lloyd
May
The University of Auckland
The Bioengineering Institute
This is a CellML description of Soboleva et al.'s 2005 mathematical model of prolactin-receptor interaction and the corollary for prolactin receptor gene expression in skin.
Journal of Theoretical Biology
Mathematical modelling of prolactin-receptor interaction and the corollary for prolactin receptor gene expression in skin
234
289
298
c.lloyd@auckland.ac.nz
Catherine Lloyd
2005-05-21
I
Vetharaniam
2007-10-02T00:00:00+00:00