Modelling the Hypothalamic Control of Growth Hormone Secretion
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.
- SourceAvailable from: Gareth Leng
[Show abstract] [Hide abstract]
- "Besides the oxytocin model reviewed above, there are mathematical models of the pulsatile secretion of LHRH (Gordan et al., 1998; Scullion et al., 2004; Khadra and Li, 2006), the hypothalamic control of growth hormone secretion (MacGregor and Leng, 2005), and the bursting properties of vasopressin (Roper et al., 2004), etc. The recent model for LHRH revealed that LHRH plays the roles of feedback regulator and a diffusive synchronization effects in pulsatile secretion of LHRH from hypothalamic neurons. "
ABSTRACT: Classically, information processing in the brain involves fast signaling mechanisms at a vast number of discrete sites, via spike-dependent neurotransmitter release at synapses. However, neurons also use a huge diversity of slower analog signaling mechanisms, these chemical signaling pathways, acting in a more global spatial scale and on a longer temporal scale, are closely related to social behaviors and emotion. How do these parallel signaling systems interact to give rise to coherent behavioral consequences? In this review, we consider the role of the neuropeptide oxytocin in the milk-ejection reflex as an example of how a complex neural network involving a peptidergic signaling pathway underlies the complex physiological behavior.Journal of Biotechnology 09/2010; 149(3):215-25. DOI:10.1016/j.jbiotec.2010.01.003 · 2.88 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Neuropeptides that are released from dendrites, such as oxytocin and vasopressin, function as autocrine or paracrine signals at their site of origin, but can also act at distant brain targets to evoke long-lasting changes in behaviour. Oxytocin, for instance, has profound effects on social bonding that are exerted at sites that richly express oxytocin receptors, but which are innervated by few, if any, oxytocin-containing projections. How can a prolonged, diffuse signal have coherent behavioural consequences? The recently demonstrated ability of neuropeptides to prime vesicle stores for activity-dependent release could lead to a temporary functional reorganization of neuronal networks harbouring specific peptide receptors, providing a substrate for long-lasting effects.Nature reviews Neuroscience 03/2006; 7(2):126-36. DOI:10.1038/nrn1845 · 31.38 Impact Factor