Keenan Daniel M, Evans William S, Veldhuis Johannes D
Department of Statistics, General Clinical Research Center, University of Virginia, Charlottesville, 22908, USA.
Am J Physiol Endocrinol Metab. 2003 Nov;285(5):E938-48. doi: 10.1152/ajpendo.00133.2003.
Hypothalamic neurons generate discrete bursts of gonadotropin-releasing hormone (GnRH) and thereby pulses of luteinizing hormone (LH) at randomly timed intervals centered on a probabilistic mean frequency. We tested the hypothesis that physiological mechanisms govern not only the number but also the stochastic dispersion of the GnRH/LH pulse-renewal process in humans; for example, in young women in the early (EF) and late (LF) follicular and midluteal (ML) phases of the menstrual cycle (n = 18) and in postmenopausal individuals (PM, n = 16). To this end, we quantify stochastic interpulse variability by way of the order-independent, two-parameter Weibull renewal process (Keenan DM and Veldhuis J. Am J Physiol Regul Integr Comp Physiol 281: R1917-R1924, 2001) and the sequence-specific, model-free approximate-entropy statistic (ApEn) (Pincus SM. Proc Natl Acad Sci USA 88: 2297-2301, 1991). Statistical testing unveiled 1) reduced probabilistic mean LH secretory-burst frequency (lower lambda of the Weibull distribution) in ML compared with each of EF, LF, and PM (P < 0.001); 2) quantifiably more regular LH interburst-interval sets (elevated gamma of the Weibull density) in PM than in each of EF, LF, and ML (P < 0.01); 3) uniquely prolonged latency to maximal LH secretion within individual secretory bursts in ML (P < 0.01); and 4) comparably mean random, sequential LH interburst-interval and mass values (normalized ApEn) among the distinct hormonal milieus. From these data, we postulate that sex steroids and age determine daily LH secretory-burst number, quantifiable pulse-renewal variability, and secretory-waveform evolution.
下丘脑神经元产生离散的促性腺激素释放激素（GnRH）脉冲，从而以概率平均频率为中心，在随机的时间间隔内产生促黄体生成素（LH）脉冲。我们检验了这样一种假设，即生理机制不仅控制人类GnRH/LH脉冲更新过程的数量，还控制其随机离散度；例如，在月经周期卵泡早期（EF）和晚期（LF）以及黄体中期（ML）的年轻女性（n = 18）和绝经后个体（PM，n = 16）中。为此，我们通过与顺序无关的双参数威布尔更新过程（Keenan DM和Veldhuis，《美国生理学杂志：调节、整合与比较生理学》281: R1917 - R1924，2001）和序列特异性、无模型的近似熵统计量（ApEn）（Pincus SM，《美国国家科学院院刊》88: 2297 - 2301，1991）来量化随机脉冲间期变异性。统计检验揭示：1）与EF、LF和PM相比，ML期的概率平均LH分泌脉冲频率降低（威布尔分布的λ值更低）（P < 0.001）；2）与EF、LF和ML相比，PM期的LH脉冲间期集的规律性更高（威布尔密度的γ值升高）（P < 0.01）；3）ML期个体分泌脉冲内达到最大LH分泌的延迟时间独特延长（P < 0.01）；4）在不同的激素环境中，LH脉冲间期和质量值的平均随机顺序（归一化ApEn）相当。根据这些数据，我们推测性类固醇和年龄决定每日LH分泌脉冲数量、可量化的脉冲更新变异性以及分泌波形演变。
