A mathematical model of diurnal variations in human plasma melatonin levels
A mathematical model of diurnal variations in human plasma melatonin levels
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DOI：
10.1152/ajpendo.1997.272.3.e506
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发表时间：
1997-03-01
影响因子：
5.1
通讯作者：
Czeisler, CA
中科院分区：
文献类型：
--
作者：
Brown, EN;Choe, Y;Czeisler, CA
对动物和人类的研究表明，血浆褪黑激素水平的日模式是由于激素的合成速率、循环输注和清除、合成开始和偏移的昼夜节律控制、环境光照条件和褪黑激素免疫测定中的错误。建立了该激素的二维线性微分方程模型，并用于分析18例正常健康男性受试者在固定常规过程中的血浆褪黑激素水平。最近开发的贝叶斯统计程序用于将免疫测定误差的大小正确地纳入分析。估计参数[中位数（范围）]为：清除半衰期23.67 (14.79 ~ 59.93)min，合成起始时间2206(1940 ~ 0029)，合成偏移时间0621(0244 ~ 0817)，最大n -乙酰转移酶活性7.17 (2.34 ~ 17.93)pmol。l(1)。分钟(1)。所有这些都与以前报告的值很好地一致。合成偏移时间与核心温度最低相差为1 h 15 min （-4 h 38 min-2 h 43 min）。合成起始与暗光褪黑素起始的相关性为0.93。我们的模型提供了一个生理上更合理的褪黑激素合成开始时间的估计，而不是昏暗光线下褪黑激素开始的估计，也是估计合成偏移相位的第一个可靠方法。我们的分析表明，褪黑激素的昼夜节律和药代动力学参数可以从单一模型中可靠地估计出来。
Studies in animals and humans suggest that the diurnal pattern in plasma melatonin levels is due to the hormone's rates of synthesis, circulatory infusion and clearance, circadian control of synthesis onset and offset, environmental lighting conditions, and error in the melatonin immunoassay. A two-dimensional linear differential equation model of the hormone is formulated and is used to analyze plasma melatonin levels in 18 normal healthy male subjects during a constant routine. Recently developed Bayesian statistical procedures are used to incorporate correctly the magnitude of the immunoassay error into the analysis. The estimated parameters [median (range)] were clearance half-life of 23.67 (14.79-59.93) min, synthesis onset time of 2206 (1940-0029), synthesis offset time of 0621 (0246-0817), and maximum N-acetyltransferase activity of 7.17 (2.34-17.93) pmol . l(-1). min(-1). All were in good agreement with values from previous reports. The difference between synthesis offset time and the phase of the core temperature minimum was 1 h 15 min (-4 h 38 min-2 h 43 min). The correlation between synthesis onset and the dim light melatonin onset was 0.93. Our model provides a more physiologically plausible estimate of the melatonin synthesis onset time than that given by the dim light melatonin onset and the first reliable means of estimating the phase of synthesis offset. Our analysis shows that the circadian and pharmacokinetics parameters of melatonin can be reliably estimated from a single model.