Origin of ultradian pulsatility in the hypothalamic-pituitary-adrenal axis.
Origin of ultradian pulsatility in the hypothalamic-pituitary-adrenal axis.
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DOI：
10.1098/rspb.2009.2148
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发表时间：
2010-06-07
期刊：
影响因子：
--
通讯作者：
Lightman SL
中科院分区：
文献类型：
--
作者：
Walker JJ;Terry JR;Lightman SL
下丘脑-垂体-肾上腺（HPA）轴是调节重要糖皮质激素循环水平的神经内分泌系统。HPA轴的活动不仅具有典型的昼夜节律，而且具有糖皮质激素离散脉冲释放的超昼夜模式。许多精神和代谢疾病与糖皮质激素脉动性的变化有关，现在很清楚，糖皮质激素反应基因以生物学上有意义的方式对这些快速波动作出反应。理论建模使我们能够确定和探索潜在的机制，在这个轴，迄今尚未成功地确定超日活动。我们证明，在垂体-肾上腺系统的前馈和反馈回路的延迟相结合，足以引起ultradian脉动在没有ultradian源从垂体上的网站。此外，我们的模型使我们能够预测垂体门静脉促肾上腺皮质激素释放激素水平的变化介导的糖皮质激素释放的不同模式，结果与我们的实验在体内的数据。
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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