Friend K, Iranmanesh A, Veldhuis J D
Department of Medical Specialties, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
J Clin Endocrinol Metab. 1996 Oct;81(10):3746-53. doi: 10.1210/jcem.81.10.8855833.
Endocrine glands signal their remote target tissues via physiologically pulsatile release of regulatory molecules. A cardinal assumption of most pathophysiological experiments is that discrete attributes of pulsatile hormone secretion are stable over successive untreated observation intervals; i.e. repeated measurements show serial within-subject reproducibility. To test this hypothesis in the GH axis, we sampled blood every 10 min for 48 h in 14 healthy men (age range, 29-77 yr; body mass index, 21-51 kg/m2). The 2 consecutive 24-h serum profiles were subjected to ultrasensitive GH chemiluminescence assay (sensitivity, 0.002 micrograms/L) with a new dose-dependent variance model to estimate within-assay precision. We then applied deconvolution analysis to estimate the number, mass, amplitude, and duration of underlying GH secretory bursts as well as simultaneously calculate the apparent GH half-life and any concurrent basal hormone secretion. Test-retest consistency was assessed by the Pearson correlation coefficient, and differences were determined by paired nonparametric (Wilcoxon) testing. Comparing successive 24-h profiles, no significant differences existed in any of the foregoing secretion or half-life measures or in a novel estimate of the relative disorderliness of hormone release, namely approximate entropy. Correlation was minimal for secretory burst amplitude and half-duration. In contrast, the calculated mean mass of GH secreted per burst was highly conserved across sessions within subjects, with an r value of 0.932 (P < 10(-6). This correlation equaled or exceeded that of mean and integrated serum GH concentrations on consecutive days (r = 0.920; P = 0.00003). The calculated daily GH production rate was also strongly reproduced (r = 0.784; P = 0.0009). Moreover, the within-subject GH half-life and GH secretory burst frequency estimates were well correlated on successive days (P = 0.034-0.004; r = 0.568-0.711). Approximate entropy values were consistent at r = 0.837 (P = 0.0019). In addition, basal GH secretion rates correlated at r = 0.622 (P = 0.0176). We conclude that homeostatic control mechanisms within the GH-insulin-like growth factor I axis strongly preserve the day to day mean mass of GH secreted per burst and the serial orderliness of the GH release process in individual healthy men across a wide span of ages and body compositions.
内分泌腺通过调节分子的生理性脉冲式释放向其远处的靶组织发出信号。大多数病理生理学实验的一个基本假设是,脉冲式激素分泌的离散特征在连续未处理的观察期内是稳定的;即重复测量显示受试者内具有序列可重复性。为了在生长激素(GH)轴上验证这一假设,我们在14名健康男性(年龄范围29 - 77岁;体重指数21 - 51 kg/m²)中每10分钟采集一次血样,共采集48小时。对连续两个24小时的血清样本进行超灵敏GH化学发光测定(灵敏度为0.002微克/升),采用新的剂量依赖性方差模型来估计测定内精密度。然后应用去卷积分析来估计潜在GH分泌脉冲的数量、质量、幅度和持续时间,并同时计算表观GH半衰期以及任何同时存在的基础激素分泌。通过Pearson相关系数评估重测一致性,通过配对非参数(Wilcoxon)检验确定差异。比较连续的24小时样本,在上述任何分泌或半衰期测量指标以及激素释放相对无序度的新估计值(即近似熵)方面均无显著差异。分泌脉冲幅度和半持续时间的相关性最小。相反,计算得出的每次脉冲分泌的GH平均质量在受试者内各时段高度保守,r值为0.932(P < 10⁻⁶)。这种相关性等于或超过了连续两天的平均血清GH浓度和积分血清GH浓度的相关性(r = 0.920;P = 0.00003)。计算得出的每日GH产生率也具有很强的可重复性(r = 0.784;P = 0.0009)。此外,连续几天内受试者内GH半衰期和GH分泌脉冲频率估计值具有良好的相关性(P = 0.034 - 0.004;r = 0.568 - 0.711)。近似熵值在r = 0.837时保持一致(P = 0.0019)。此外,基础GH分泌率的相关性为r = 0.622(P = 0.0176)。我们得出结论,在GH - 胰岛素样生长因子I轴内的稳态控制机制在很大年龄范围和身体组成的个体健康男性中,有力地维持了每次脉冲分泌的GH每日平均质量以及GH释放过程的序列有序性。