Modeling the hypothalamus-pituitary-adrenal system: homeostasis by interacting positive and negative feedback
Modeling the hypothalamus-pituitary-adrenal system: homeostasis by interacting positive and negative feedback
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DOI：
10.1007/s10867-009-9134-3
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发表时间：
2009-05-01
影响因子：
1.8
通讯作者：
Peters, Achim
中科院分区：
文献类型：
--
作者：
Conrad, Matthias;Hubold, Christian;Peters, Achim
下丘脑-垂体-肾上腺（HPA）系统与压力和体内平衡的恢复密切相关。该系统在后半夜受到刺激，白天的活动减少，并在深夜达到稳态水平。在本文中，我们推导并讨论了 HPA 系统的一种新模型。它基于构成体内平衡原则的三个简单规则，并且仅包括最实质性的生理要素。与其他模型相比，除了传统的负反馈成分之外，其主要组成部分还包括正反馈回路。为了验证该模型，我们提出了一种参数估计程序，使人们能够使模型适应临床观察。使用这种方法，我们能够证明新模型能够模拟临床试验。此外，还研究了系统的稳态。我们表明，在温和条件下，系统始终具有明确定义的设定点，该设定点反映了要建模的临床情况。最后，计算出的参数可以从生理角度进行解释，从而深入了解抑郁症、肥胖症或糖尿病等疾病。
The hypothalamus-pituitary-adrenal (HPA) system is closely related to stress and the restoration of homeostasis. This system is stimulated in the second half of the night, decreases its activity in the daytime, and reaches the homeostatic level during the late evening. In this paper, we derive and discuss a novel model for the HPA system. It is based on three simple rules that constitute a principle of homeostasis and include only the most substantive physiological elements. In contrast to other models, its main components include, apart from the conventional negative feedback ingredient, a positive feedback loop. To validate the model, we present a parameter estimation procedure that enables one to adapt the model to clinical observations. Using this methodology, we are able to show that the novel model is capable of simulating clinical trials. Furthermore, the stationary state of the system is investigated. We show that, under mild conditions, the system always has a well-defined set-point, which reflects the clinical situation to be modeled. Finally, the computed parameters may be interpreted from a physiological point of view, thereby leading to insights about diseases like depression, obesity, or diabetes.