St Hilaire Melissa A, Gronfier Claude, Zeitzer Jamie M, Klerman Elizabeth B
Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
J Pineal Res. 2007 Oct;43(3):294-304. doi: 10.1111/j.1600-079X.2007.00477.x.
The rhythm of plasma melatonin concentration is currently the most accurate marker of the endogenous human circadian pacemaker. A number of methods exist to estimate circadian phase and amplitude from the observed melatonin rhythm. However, almost all these methods are limited because they depend on the shape and amplitude of the melatonin pulse, which vary among individuals and can be affected by environmental influences, especially light. Furthermore, these methods are not based on the underlying known physiology of melatonin secretion and clearance, and therefore cannot accurately quantify changes in secretion and clearance observed under different experimental conditions. A published physiologically-based mathematical model of plasma melatonin can estimate synthesis onset and offset of melatonin under dim light conditions. We amended this model to include the known effect of melatonin suppression by ocular light exposure and to include a new compartment to model salivary melatonin concentration, which is widely used in clinical settings to determine circadian phase. This updated model has been incorporated into an existing mathematical model of the human circadian pacemaker and can be used to simulate experimental protocols under a number of conditions.
血浆褪黑素浓度的节律目前是人体内在昼夜节律起搏器最准确的标志物。存在多种从观察到的褪黑素节律估计昼夜节律相位和振幅的方法。然而，几乎所有这些方法都有局限性，因为它们依赖于褪黑素脉冲的形状和振幅，而这些在个体之间存在差异，并且可能受到环境影响，尤其是光照的影响。此外，这些方法并非基于褪黑素分泌和清除的潜在已知生理学原理，因此无法准确量化在不同实验条件下观察到的分泌和清除变化。一个已发表的基于生理学的血浆褪黑素数学模型可以估计暗光条件下褪黑素的合成开始和结束时间。我们对该模型进行了修正，以纳入眼部光照对褪黑素抑制的已知效应，并纳入一个新的隔室来模拟唾液褪黑素浓度，唾液褪黑素浓度在临床环境中广泛用于确定昼夜节律相位。这个更新后的模型已被纳入现有的人体昼夜节律起搏器数学模型中，并可用于模拟多种条件下的实验方案。
