Keenan D M, Veldhuis J D
Department of Statistics, University of Virginia, Charlottesville, VA 22903, USA.
Am J Physiol Regul Integr Comp Physiol. 2001 Dec;281(6):R1917-24. doi: 10.1152/ajpregu.2001.281.6.R1917.
The incremental nature of neuroendocrine aging suggests that subtle system dysregulation may precede overt axis failure. The present analyses unmask threefold disruption of pulsatile gonadotropin-releasing hormone (GnRH)-luteinizing hormone (LH) secretion in the aging male. First, by way of random effects-based deconvolution analysis, we document an elevated daily GnRH-LH pulse frequency in healthy older men [namely, mean (+/-SE) 23 +/- 1 (older) vs. 15 +/- 1 (young) LH secretory bursts/24 h, P < 0.001] and lower mean LH pulse mass [3.73 +/- 0.58 (older) vs. 5.46 +/- 0.66 (young) IU/l, P = 0.038]. However, total LH secretion rates and two-compartment LH elimination kinetics were comparable in the two age cohorts. Second, using the approximate entropy statistic, we show an equivalently random order-dependent succession of LH interpulse-interval lengths in young and older men, but a marked age-related deterioration of the ad seriatim regularity of LH pulse mass series in older individuals (P = 0.0057). Third, by modeling GnRH pulse-generator output as a Weibull renewal process (generalized Gamma density) to emulate loosely coupled GnRH neuronal oscillators, we identify an age-related reduction in the frequency-independent and order-independent variability of GnRH-LH interpulse-interval sets (P = 0.08). These findings indicate that the GnRH-LH pulsing mechanism in healthy older men maintains an increased mean frequency and lower amplitude of bursting activity, a reduced uniformity of serial LH pulse-mass values, and an impaired variability among interpulse-interval lengths. Thereby, the foregoing order-dependent and order-independent alterations in GnRH-LH signal generation in the aging human suggest a general framework for exploring subtle disruption of time-sensitive regulation of other neurointegrative systems.
神经内分泌衰老的渐进性表明，在明显的轴功能衰竭之前可能存在细微的系统失调。目前的分析揭示了衰老男性中促性腺激素释放激素（GnRH）-黄体生成素（LH）脉冲分泌的三重破坏。首先，通过基于随机效应的去卷积分析，我们记录到健康老年男性每日GnRH-LH脉冲频率升高[即，平均（±标准误）23±1（老年）对15±1（年轻）次LH分泌脉冲/24小时，P<0.001]，且平均LH脉冲量较低[3.73±0.58（老年）对5.46±0.66（年轻）IU/L，P = 0.038]。然而，两个年龄组的总LH分泌率和两室LH消除动力学相当。其次，使用近似熵统计，我们表明年轻和老年男性中LH脉冲间期长度的序列依赖性相继顺序同样随机，但老年个体中LH脉冲量序列的逐次规律性明显与年龄相关地恶化（P = 0.0057）。第三，通过将GnRH脉冲发生器输出建模为威布尔更新过程（广义伽马密度）以模拟松散耦合的GnRH神经元振荡器，我们发现GnRH-LH脉冲间期集的频率无关和顺序无关变异性随年龄增长而降低（P = 0.08）。这些发现表明，健康老年男性中的GnRH-LH脉冲机制维持了爆发活动的平均频率增加和幅度降低、LH脉冲量序列值的均匀性降低以及脉冲间期长度之间的变异性受损。因此，衰老人类中GnRH-LH信号生成的上述顺序依赖性和顺序无关性改变为探索其他神经整合系统的时间敏感调节的细微破坏提供了一个总体框架。
