A biomathematical model of time-delayed feedback in the human male hypothalamic-pituitary Leydig cell axis
A biomathematical model of time-delayed feedback in the human male hypothalamic-pituitary Leydig cell axis
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DOI：
10.1152/ajpendo.1998.275.1.e157
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发表时间：
1998-07-01
影响因子：
5.1
通讯作者：
Veldhuis, JD
中科院分区：
文献类型：
--
作者：
Keenan, DM;Veldhuis, JD
我们开发，实施和测试的反馈和前馈生物数学结构的男性下丘脑[促性腺激素释放激素（GnRH）]-垂体[促黄体生成激素（LH）]-性腺[睾酮（Te）]轴。这个随机微分方程制剂由一个非平稳随机点过程负责产生的GnRH，这是负调制的短环（GnRH）和长环（Te）反馈的情景释放。脉冲式GnRH释放进而通过激动性剂量-反应曲线驱动LH分泌爆发，该曲线部分地被Te负反馈抑制。循环LH刺激（前馈）Te的合成和释放的第二剂量反应。Te通过负剂量反应反馈作用于GnRH和LH输出，从而满足闭环控制系统的条件。四个计算机模拟文件预期的反馈性能，如先前发表的人类男性GnRH-LH-Te轴。其他六个模拟测试不同的模型内的耦合机制，以连接一个昼夜节律调节输入的脉动控制节点，以解释已知的24小时的变化Te，并在较小程度上，LH。我们的结论是，相关的动态功能，节点间的剂量依赖性的监管连接，并在系统内的时间延迟耦合一起提供了一个生物数学基础的非线性反馈-前馈控制模型相结合的脉动和昼夜节律的功能，密切模仿男性下丘脑-垂体-leydig细胞轴的可测量的输出活动。
We develop, implement, and test a feedback and feedforward biomathematical construct of the male hypothalamic [gonadotropin-releasing hormone (GnRH)]-pituitary [luteinizing hormone (LH)]-gonadal [testosterone (Te)] axis. This stochastic differential equation formulation consists of a nonstationary stochastic point process responsible for generating episodic release of GnRH, which is modulated negatively by short-loop (GnRH) and long-loop (Te) feedback. Pulsatile GnRH release in turn drives bursts of LH secretion via an agonistic dose-response curve that is partially damped by Te negative feedback. Circulating LH stimulates (feedforward) Te synthesis and release by a second dose response. Te acts via negative dose-responsive feedback on GnRH and LH output, thus fulfilling conditions of a closed-loop control system. Four computer simulations document expected feedback performance, as published earlier for the human male GnRH-LH-Te axis. Six other simulations test distinct within-model coupling mechanisms to link a circadian modulatory input to a pulsatile control node so as to explicate the known 24-h variations in Te and, to a lesser extent, LH. We conclude that relevant dynamic function, internodal dose-dependent regulatory connections, and within-system time-delayed coupling together provide a biomathematical basis for a nonlinear feedback-feedforward control model with combined pulsatile and circadian features that closely emulate the measurable output activities of the male hypothalamic-pituitary-leydig cell axis.