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首页> 外文期刊>Journal of Theoretical Biology >Mathematical modelling of prolactin-receptor interaction and the corollary for prolactin receptor gene expression in skin
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Mathematical modelling of prolactin-receptor interaction and the corollary for prolactin receptor gene expression in skin

机译：催乳素受体相互作用的数学模型和皮肤中催乳素受体基因表达的推论

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A mathematical model of prolactin regulating its own receptors was developed, and compared with experimental data on a qualitative level. The model incorporates the kinetics of prolactin-receptor interactions and subsequent signalling by prolactin-receptor dimers to regulate the production of receptor mRNA and hence the receptor population. The model relates changes in plasma prolactin concentration to prolactin receptor (PRLR) gene expression, and can be used for predictive purposes. The cell signalling that leads to the activation of target genes, and the mechanisms for regulation of transcription, were treated empirically in the model. The model's parameters were adjusted so that model simulations agreed with experimentally observed responses to administration of prolactin in sheep. In particular, the model correctly predicts insensitivity of receptor mRNA regulation to a series of subcutaneous injections of prolactin, versus sensitivity to prolonged infusion of prolactin. In the latter case, response was an acute down-regulation followed by a prolonged up-regulation of mRNA, with the magnitude of the up-regulation increasing with the duration of infusion period. The model demonstrates the feasibility of predicting the in vivo response of prolactin target genes to external manipulation of plasma prolactin, and could provide a useful tool for identifying optimal prolactin treatments for desirable outcomes. (c) 2004 Elsevier Ltd. All rights reserved.
机译：建立了催乳素调节自身受体的数学模型，并在定性水平上与实验数据进行了比较。该模型结合了催乳激素-受体相互作用的动力学和随后的催乳素-受体二聚体信号传导，以调节受体mRNA的产生，从而调节受体群体。该模型将血浆催乳素浓度的变化与催乳素受体（PRLR）基因表达相关，可用于预测目的。在模型中凭经验处理导致靶基因活化的细胞信号传导和转录调节机制。调整模型的参数，以使模型模拟与实验观察到的对绵羊催乳素给药的反应一致。特别地，该模型正确预测了受体mRNA调节对一系列催乳素皮下注射的不敏感性，与对长期输注催乳素的敏感性相比。在后一种情况下，反应是急性下调，随后是mRNA的上调，上调的幅度随输液时间的延长而增加。该模型证明了预测催乳激素靶基因对血浆催乳素的外部操作的体内反应的可行性，并且可以为鉴定理想催乳素的理想治疗方法提供有用的工具。 （c）2004 Elsevier Ltd.保留所有权利。

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