Modelling the hypothalamic control of growth hormone secretion: the full pituitary + hypothalamic model

Model Status

This particular CellML model describes the full (pituitary + hypothalamic) model of the published article. The units have been checked and are consistent, and the model runs in OpenCell and COR to replicate the published results (as shown in figure 12 of the paper).

Model Structure

Abstract: Here, we construct a mathematical model of the hypothalamic systems that control the secretion of growth hormone (GH). The work extends a recent model of the pituitary GH system, adding representations of the hypothalamic GH-releasing hormone (GHRH) and somatostatin neurones, each modelled as a single synchronised unit. An unpatterned stochastic input drives the GHRH neurones generating pulses of GHRH release that trigger GH pulses. Delayed feedback from GH results in increased somatostatin release, which inhibits both GH secretion and GHRH release, producing an overall pattern of 3-h pulses of GH secretion that is very similar to the secretory profile observed in male rats. Rather than directly stimulating somatostatin release, GH feedback triggers a priming effect, increasing releasable stores of somatostatin. Varying this priming effect to reduce the effect of GH can reproduce the less pulsatile form of GH release observed in the female rat. The model behaviour is tested by comparison with experimental observations with a range of different experimental protocols involving GHRH injections and somatostatin and GH infusion.

The complete original paper reference is cited below:

Modelling the hypothalamic control of growth hormone secretion, D. J. MacGregor and G. Leng, 2005, Journal of Neuroendocrinology, volume 17, 788-803. PubMed ID: 16280026

A schematic diagram of the different components and connections in the growth hormone secretory system. Somatostatin (SOM) inhibits the secretion of both growth hormone-releasing hormone (GHRH) and growth hormone (GH). After a delay, GH feeds back to prime the pool of releasable somatostatin, resulting in the bulk release of somatostatin, which in turn allows further GHRH release and and another burst of GH.