Gonzalez-Heydrich J, Steingard R J, Kohane I
Psychopharmacology Clinic, Department of Psychiatry, Children's Hospital, Boston.
Proc Annu Symp Comput Appl Med Care. 1994:1010.
This paper describes the construction of a computer model that simulates the hypothalamic-pituitary-adrenal axis (HPA axis) regulation of cortisol production. It is presented to illustrate the process of physiological modeling using standard "off the shelf" technologies. The model simulates components of the HPA axis involved in the continuous secretion and elimination of cortisol, adrenocorticotropin (ACTH), and corticotropin releasing hormone (CRH). The physiological relations of these component pieces were modeled based on the current knowledge of their functioning. Rate constants, half lives, and receptor affinities were assigned values derived from the experimental literature. At its current level of development the model is able to accurately simulate the timing, magnitude and decay of the ACTH and cortisol concentration peaks resulting from the ovine-CRH stimulation test in normal and hypercortisolemic patients. The model will be used to predict the effects of lesions in different components of the HPA axis on the time course of cortisol and ACTH levels. We plan to use the model to explore the experimental conditions required to distinguish mechanisms underlying various disorders of the HPA axis, particularly depression. Efforts are currently underway to validate the model for a large variety of normal and pathological perturbations of the HPA axis.
本文描述了一个计算机模型的构建，该模型模拟下丘脑 - 垂体 - 肾上腺轴（HPA轴）对皮质醇分泌的调节。展示此模型是为了说明使用标准“现成”技术进行生理建模的过程。该模型模拟了HPA轴中参与皮质醇、促肾上腺皮质激素（ACTH）和促肾上腺皮质激素释放激素（CRH）持续分泌与消除的组成部分。这些组成部分的生理关系是根据其当前已知的功能进行建模的。速率常数、半衰期和受体亲和力被赋予了从实验文献中得出的值。在其当前的发展水平下，该模型能够准确模拟正常和高皮质醇血症患者在羊CRH刺激试验中ACTH和皮质醇浓度峰值的时间、幅度和衰减。该模型将用于预测HPA轴不同组成部分的损伤对皮质醇和ACTH水平时间进程的影响。我们计划使用该模型来探索区分HPA轴各种紊乱（特别是抑郁症）潜在机制所需的实验条件。目前正在努力验证该模型对HPA轴各种正常和病理扰动的适用性。
