Modelling the Hypothalamic Control of Growth Hormone Secretion

Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, George Square, Edinburgh, UK.
Journal of Neuroendocrinology (Impact Factor: 3.14). 01/2006; 17(12):788-803. DOI: 10.1111/j.1365-2826.2005.01370.x
Source: PubMed


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.

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    • "This assumption appears to be satisfied for the testosterone hormonal regulation (see, e.g., [10]) but not for pulsatile endocrine loops in general. For instance, in [19], where hypothalamic control of the growth hormone (GH) secretion is considered, the time delay for the stimulation by GH of the releasable store of somatostatin is estimated to 60 minutes. The experimental data provided by [20] demonstrate that, for adolescent females , the estimated GH interburst interval is less than an hour, while for young males it is usually greater, but can be less than an hour at certain time intervals. "
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    ABSTRACT: The role of the time delay value in the dynamics of a hybrid model of pulsatile feedback endocrine regulation is investigated. The model in hand can be seen as an impulsive and delayed version of the popular in computational biology Goodwin Oscillator, where the feedback is implemented by means of pulse modulation. The value of the time delay is related to the duration of the time interval between the firing times of the feedback impulses. Under the assumption of a cascade structure of the continuous part of the model, the hybrid dynamics of the closed-loop system are shown to be governed by a discrete mapping propagating through the firing times of the impulsive feedback. Conditions for existence and stability of periodic solutions of the model are obtained. Bifurcation analysis of the mapping reveals the phenomenon of bistability arising for larger time delay values but not observed for the smaller ones.
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    • "Development and testing of the model is in custom software built in C++ and wxWidgets, based on modelling and data analysis software we have previously developed to study diverse neuroendocrine systems (MacGregor and Leng, 2005; Macgregor and Lincoln, 2008; MacGregor et al., 2009). "
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    • "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. "
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