Origin of ultradian pulsatility in the hypothalamic-pituitary-adrenal axis

JJ Walker, JR Terry, SL Lightman

Research output: Contribution to journalArticle (Academic Journal)peer-review

152 Citations (Scopus)

Abstract

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.
Translated title of the contributionOrigin of ultradian pulsatility in the hypothalamic-pituitary-adrenal axis
Original languageEnglish
Pages (from-to)1627 - 1633
Number of pages7
JournalProceedings of the Royal Society B: Biological Sciences
Volume277
DOIs
Publication statusPublished - Jun 2010

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