Mathematical modeling of gonadotropin-releasing hormone signaling.
Mathematical modeling of gonadotropin-releasing hormone signaling.
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DOI：
10.1016/j.mce.2016.08.022
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发表时间：
2017-07-05
影响因子：
4.1
通讯作者：
McArdle CA
中科院分区：
文献类型：
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作者：
Pratap A;Garner KL;Voliotis M;Tsaneva-Atanasova K;McArdle CA
促性腺激素释放激素（GnRH）通过G蛋白偶联受体作用于垂体促性腺激素细胞以控制生殖。这些是Gq偶联受体，介导GnRH对促黄体生成素（LH）和促卵泡激素（FSH）的胞吐分泌的急性作用，以及对它们合成的慢性调节。GnRH以短脉冲分泌，GnRH对其靶细胞的作用取决于这些脉冲的动力学。在这里，我们概述了GnRH受体及其信号网络，重点放在脉动信号，以及如何机械的数学模型和信息理论的方法有助于进一步这一领域。我们描述了一个GnRH作用的机制模型，通过其Gq/11偶联受体。GnRH以脉冲形式分泌，可提高信号传导效率和稳健性。最大反应发生在次最大GnRH脉冲频率下。这可能反映了不相干的前馈回路，但不是上游负反馈。单细胞测量揭示了具有显著信息丢失的噪声信号系统。
Gonadotropin-releasing hormone (GnRH) acts via G-protein coupled receptors on pituitary gonadotropes to control reproduction. These are Gq-coupled receptors that mediate acute effects of GnRH on the exocytotic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as the chronic regulation of their synthesis. GnRH is secreted in short pulses and GnRH effects on its target cells are dependent upon the dynamics of these pulses. Here we overview GnRH receptors and their signaling network, placing emphasis on pulsatile signaling, and how mechanistic mathematical models and an information theoretic approach have helped further this field. We describe a mechanistic model for GnRH action via its Gq/11-coupled receptors. GnRH is secreted is pulses which can increase signaling efficiency and robustness. Maximal responses occur at sub-maximal GnRH pulse frequency. This may reflect incoherent feedforward loops but not upstream negative feedback. Single cell measures reveal noisy signaling systems with marked information loss.