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促性腺激素释放激素作用下 LH 反应的双通路数学模型可预测自促性腺激素释放激素脉冲发生

A Two-Pathway Mathematical Model of the LH Response to GnRH that Predicts Self-Priming.

机构信息

Centre for Neuroendocrinology, University of Otago, Christchurch, New Zealand ; MacDiarmid Institute for Advanced Materials and Nanoengineering, University of Otago, Christchurch, New Zealand ; Department of Obstetrics and Gynaecology, University of Otago, Christchurch, New Zealand.

出版信息

Int J Endocrinol. 2013;2013:410348. doi: 10.1155/2013/410348. Epub 2013 Nov 11.

DOI:10.1155/2013/410348
PMID:24319456
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3844275/
Abstract

An acute response of LH to a stimulatory pulse of GnRH is modelled as a result of a pathway (Pathway I) that consists of two compartments including a single (rate limiting) intermediate. In addition, a second pathway (Pathway II) was added, consisting of an intermediate transcription factor and subsequently a synthesised protein. Pathway II had a delayed effect on LH release due to the time taken to produce the intermediate protein. The model included synergism between these two pathways, which yielded an augmented response. The model accounts for a number of observations, including GnRH self-priming and the biphasic pattern of LH response. The same model was used to fit the data of the LH response when gonadotrophs responded to the addition of oxytocin in the response with a shoulder on the profile. Pathway I is able to be conceptualised as the basic Ca(2+)-mediated pathway. Pathway II contains features characteristic of the cAMP-mediated pathway. Thus, we have provided an explanation for details of the nature of the profile of LH secretion and additionally enabled incorporation of cAMP in an integrating model. The study investigated the possibility of two interacting pathways being at the basis of both the shoulder on the LH surges and self-priming, and the model illustrates that this appears to be highly likely.

摘要

黄体生成素对 GnRH 刺激脉冲的急性反应被建模为一条途径(途径 I)的结果,该途径包括两个隔室,其中包括一个单一的(限速)中间产物。此外,还添加了第二条途径(途径 II),由中间转录因子和随后合成的蛋白质组成。由于产生中间蛋白所需的时间,途径 II 对 LH 释放的影响具有延迟作用。该模型包括这两种途径之间的协同作用,产生了增强的反应。该模型解释了许多观察结果,包括 GnRH 自我启动和 LH 反应的双峰模式。相同的模型用于拟合当促性腺激素对催产素的添加做出反应时,LH 反应数据中的肩峰。途径 I 可以被概念化为基本的 Ca(2+)-介导途径。途径 II 包含与 cAMP 介导途径特征相关的特征。因此,我们对 LH 分泌曲线性质的细节提供了一个解释,并且还能够在整合模型中包含 cAMP。该研究调查了两种相互作用的途径作为 LH 波肩峰和自我启动的基础的可能性,并且该模型表明这种可能性非常高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/3844275/3539732e2bd1/IJE2013-410348.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/3844275/54dd6dd5abee/IJE2013-410348.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/3844275/478b7de2b420/IJE2013-410348.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/3844275/05d8c422af34/IJE2013-410348.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/3844275/4b4cbf4e564c/IJE2013-410348.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/3844275/3539732e2bd1/IJE2013-410348.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/3844275/54dd6dd5abee/IJE2013-410348.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/3844275/478b7de2b420/IJE2013-410348.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/3844275/05d8c422af34/IJE2013-410348.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/3844275/4b4cbf4e564c/IJE2013-410348.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/961e/3844275/3539732e2bd1/IJE2013-410348.005.jpg

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