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

Proceedings. Biological Sciences
Jamie J WalkerS L Lightman

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.

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Citations

May 28, 2013·Molecular and Cellular Endocrinology·Thomas DickmeisMeltem Weger
Feb 10, 2011·Endocrinology·Francesca SpigaStafford L Lightman
Jun 9, 2012·PLoS Biology·Jamie J WalkerStafford L Lightman
Aug 20, 2011·Endocrine Journal·Vladimir M MarkovićLjiljana Kolar-Anić
Nov 13, 2012·Critical Reviews in Biomedical Engineering·Jeremy D ScheffIoannis P Androulakis
Nov 13, 2013·Neuroscience and Biobehavioral Reviews·Nicole StrüberGerhard Roth
Nov 14, 2014·Journal of the Royal Society, Interface·J J WalkerJ R Terry
Oct 22, 2014·Mathematical Medicine and Biology : a Journal of the IMA·Vladimir M MarkovićLjiljana Kolar-Anić
Sep 28, 2014·Expert Opinion on Drug Safety·Georgina M Russell, Stafford L Lightman
Dec 17, 2015·Annual Review of Physiology·Maria A SactaInez Rogatsky
Dec 15, 2015·Neuroscience and Biobehavioral Reviews·Konstantinos KalafatakisStafford L Lightman
Dec 19, 2012·Psychoneuroendocrinology·Slavena T TrifonovaClaude P Muller
Oct 6, 2011·Physiology & Behavior·R A SarabdjitsinghE R de Kloet
Oct 12, 2010·Current Opinion in Genetics & Development·Benedicte MengelSandeep Krishna
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Jul 25, 2012·The European Journal of Neuroscience·Eleanor J WaiteStafford L Lightman
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Apr 17, 2014·Clinical Endocrinology·Georgina M RussellStafford Lightman
Mar 13, 2014·Clinical Endocrinology·David E Henley, Stafford L Lightman
Apr 3, 2016·Chaos·Željko ČupićLjiljana Kolar-Anić
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Aug 19, 2015·Mathematical Biosciences·Niyousha HosseinichimehAndrea K Wittenborn
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Feb 11, 2015·Molecular and Cellular Endocrinology·Francesca Spiga, Stafford L Lightman
Dec 3, 2014·Molecular and Cellular Endocrinology·B PeetersG Van den Berghe

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