Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, Luxembourg, Luxembourg.
Psychoneuroendocrinology. 2013 Jul;38(7):1090-101. doi: 10.1016/j.psyneuen.2012.10.016. Epub 2012 Dec 14.
Cortisol is the key effector molecule of the HPA axis and is secreted in a pulsatile manner in all species studied. In order to understand cortisol signalling in health and disease, detailed analysis of hormone pulsatility is necessary. To dissect cortisol pulsatility in plasma deconvolution techniques have been applied. Blood sampling is a labour-intensive, expensive and invasive technique that causes stress and alters HPA axis activity. Therefore saliva has been extensively investigated as an alternative sample to measure cortisol. Here we use state of the art deconvolution algorithms to investigate cortisol pulsatility in saliva. Blood and saliva samples were obtained at 15-min intervals over an 8h period in 18 healthy men to analyse their diurnal cortisol levels. A multiparameter deconvolution technique was used to generate statistically significant models of cortisol secretion and elimination in plasma and saliva. The models consisted of estimates of the number, amplitude, duration and frequency of secretory bursts as well as the elimination half-life (t1/2) in a subject specific manner. No significant differences were noted between plasma and saliva with regard to the observed secretory bursts (7.8±1.5 vs. 7.0±1.4) and the interpeak interval (59.6±10.5 min vs. 61.0±11.5 min). Moreover a strong positive correlation between the numbers of peaks in both fluids was observed (r=0.83, P<0.0001). Monte Carlo simulations revealed an 84% temporal concordance between plasma and saliva peaks in all donors (P<0.05) with a mean of 1.3±0.8 plasma peaks unmatched in saliva. The percentage concordance increased to 90% when concording only the morning cortisol peaks in plasma and saliva up to 11:00 h. The deconvolution of the most distinct component of cortisol diurnal rhythm-cortisol awakening response (CAR), revealed an average 2.5±1.1 peaks based on the individual time for cortisol to return to baseline levels. In conclusion, deconvolution analysis of plasma and salivary cortisol concentration time series showed a close correlation and similar pulsatile characteristics between saliva and plasma cortisol. Similarly, Monte Carlo simulations revealed a high concordance between the peaks in these coupled time series suggesting that saliva is a suitable medium for subsequent deconvolution analysis yielding accurate and reliable models of cortisol secretion in particular during the morning hours.
皮质醇是 HPA 轴的关键效应分子，在所有研究过的物种中均以脉冲方式分泌。为了了解皮质醇在健康和疾病中的信号转导，有必要对激素脉冲进行详细分析。为了剖析血浆中的皮质醇脉冲，已经应用了去卷积技术。采血是一种劳动强度大、费用高且具侵入性的技术，会引起应激并改变 HPA 轴的活性。因此，唾液已被广泛研究作为替代样本来测量皮质醇。在这里，我们使用最先进的去卷积算法来研究唾液中的皮质醇脉冲。在 18 名健康男性中，以 15 分钟的间隔采集血液和唾液样本，持续 8 小时，以分析他们的日间皮质醇水平。使用多参数去卷积技术生成了血浆和唾液中皮质醇分泌和消除的具有统计学意义的模型。这些模型包括以个体特异性的方式估计分泌脉冲的数量、幅度、持续时间和频率，以及消除半衰期（t1/2）。在观察到的分泌脉冲（7.8±1.5 vs. 7.0±1.4）和峰间间隔（59.6±10.5 min vs. 61.0±11.5 min）方面，血浆和唾液之间没有差异。此外，还观察到两种液体中峰数之间存在强烈的正相关（r=0.83，P<0.0001）。蒙特卡罗模拟显示，在所有供体中，血浆和唾液峰之间的时间一致性为 84%（P<0.05），其中 1.3±0.8 个血浆峰无法在唾液中匹配。当仅将血浆和唾液中的早晨皮质醇峰同步到 11:00 时，一致性百分比增加到 90%。去卷积皮质醇昼夜节律最明显的成分——皮质醇觉醒反应（CAR），显示基于皮质醇恢复到基线水平的个体时间，平均有 2.5±1.1 个峰。总之，对血浆和唾液皮质醇浓度时间序列的去卷积分析表明，唾液和血浆皮质醇之间存在密切的相关性和相似的脉冲特征。同样，蒙特卡罗模拟显示，这些耦合时间序列中的峰之间具有很高的一致性，这表明唾液是随后的去卷积分析的合适介质，特别是在早晨，可生成皮质醇分泌的准确可靠模型。
