Farhy, Bowers, Veldhuis, 2007

Model Status

This model has been curated and is known to run in PCEnv 0.2 and COR. The model is units-consistent and appears to be able to reproduce the output of the model described in the publication.

Model Structure

Neuroendocrine systems usually communicate via intermitent (pulsatile) rather than continuous (steady state) signal exchange. Hormone pulses transmit information to target tissues, for example the secretion patterns of growth hormone (GH) influence body size, lipoprotein metabolism, and insulin sensitivity. Pulsatile hormone secretion is controlled by integrative feedback mechanisms. Focusing, in particular, on GH; its secretion is stimulated by GH-releasing hormone (GHRH), is enhanced by ghrelin (GHS), and is inhibited by somatostatin (SRIF). GH feeds back into this system by regulating each of the GHRH (inhibited), SRIF (stimulated), and GHS (repressed) receptors.

The considerable complexity of neuroendocrine systems has provided an incentive for researchers to try to capture their characteristics in mathematical models. In their 2007 model, Farhy, Bowers and Veldhuis aim to explain how GHRH, SRIF, GHS and GH interact to control GH dynamics (see the figure below). Interestingly, there are sex-based differences in the pathophysiology of GH secretion: for example, the the GH pulse amplitude is two-fold greater in women than in men, while GH secretory patterns are more disorderly in women compared with in men. These sex-based differences are addressed by Farhy et al. and the two CellML models are specific to males (version 2) and females (version 2 variant 1).

The complete original paper reference is cited below:

Model-projected mechanistic bases for sex differences in growth hormone regulation in humans, Leon S. Farhy, Cyril Y. Bowers and Johannes D. Veldhuis, 2006, American Journal of Physiology. Regulatory, Integrative and Comparative Physiology , volume 17, 788-803. (Full text (HTML) and PDF versions of the article are available to subscribers on the American Journal of Physiology. Regulatory, Integrative and Comparative Physiology website.) PubMed ID: 17185408

A schematic diagram of the primary interconnections assumed among growth hormone (GH), growth hormone releasing hormone (GHRH), somatostatin (SRIF) in the periventricular nucleus (SRIF PeV) and arcuate nucleus (SRIF ArC), growth hormone secretagogues (GHS) and GH feedback in the human. The small green arrows denote greater potency (P) or efficacy (E) in women compared with men.

Please note this particular version of the model is specific to females and also GHRH alone is being injected. To simulate the injection of GHS and L-arginine the CellML model will have to be adapted slightly - this is relatively simple to do and will require changing a few initial conditions and parameters.