期刊
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
卷 277, 期 1688, 页码 1627-1633出版社
ROYAL SOC
DOI: 10.1098/rspb.2009.2148
关键词
neuroendocrine regulation; glucocorticoid hormones; ultradian pulsatility; mathematical modelling; numerical continuation
资金
- EPSRC [EP/E032249/1]
- Wellcome Trust [074112/Z/04/Z]
- BBSRC [BB/H015779/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/H015779/1] Funding Source: researchfish
The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates the circulating levels of vital glucocorticoid hormones. The activity of the HPA axis is characterized not only by a classic circadian rhythm, but also by an ultradian pattern of discrete pulsatile release of glucocorticoids. A number of psychiatric and metabolic diseases are associated with changes in glucocorticoid pulsatility, and it is now clear that glucocorticoid responsive genes respond to these rapid fluctuations in a biologically meaningful way. Theoretical modelling has enabled us to identify and explore potential mechanisms underlying the ultradian activity in this axis, which to date have not been identified successfully. We demonstrate that the combination of delay with feed-forward and feedback loops in the pituitary-adrenal system is sufficient to give rise to ultradian pulsatility in the absence of an ultradian source from a supra-pituitary site. Moreover, our model enables us to predict the different patterns of glucocorticoid release mediated by changes in hypophysial-portal corticotrophin-releasing hormone levels, with results that parallel our experimental in vivo data.
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