Veldhuis J D
Department of Internal Medicine, University of Virginia Health Sciences Center, National Science Foundation Center for Biological Timing, Charlottesville 22908, USA.
J Pediatr Endocrinol Metab. 1996 Jun;9 Suppl 3:237-53.
Neuroendocrine regulation of the somatotropic (GH) axis is under the direction of hypothalamic signals, intrapituitary mechanisms, and multi-level feedback control. Consequently, understanding the regulation of the physiologically pulsatile mode of GH release in vivo is a substantial challenge.
To present and review several new modalities designed to unmask novel features of physiological regulation of the GH axis. To this end, I emphasize gender differences in the control of pulsatile GH release, while highlighting the new approaches to uncovering such differences.
Human volunteers.
Novel investigative modalities include: (1) a high-sensitivity chemiluminescence GH assay capable of measuring 0.002 microgram/l of GH when utilized with a new discrete variance model for assay data reduction; (2) the technique of standardized linear regression to compare GH measures in men versus women; (3) the application of so-called deconvolution analysis, which is designed to estimate underlying rates of pulsatile hormone (GH) secretion as well as hormone half-life from a given plasma GH concentration profile; (4) an approximate entropy (ApEn) statistic to quantify the regularity or orderliness of hormone release, by assigning a single non-negative number that is a measure of the pattern reproducibility in the data; and (5) the evolution of network models to represent the physiological connections and feedback activities of the GH axis.
The foregoing new methodologies have collectively uncovered prominent gender differences in the regulation of the GH axis, which encompass: (i) higher mean serum GH concentrations due to greater GH secretory burst mass in women than men; (ii) relatively reduced suppressibility of GH by oral glucose administration due to greater GH secretory burst mass in women compared to men, with no apparent gender differences in the frequency of GH secretory bursts or the GH half-life in plasma; (iv) a remarkably higher degree of irregularity or disorder in the GH release process in women or female rats compared to male counterparts, indicating significantly reduced pattern reproducibility in the female; (v) an approximately two-fold greater sensitivity of men compared to women to the negative effects of age and increased percentage body fat and the positive impact of physical fitness on mean serum GH concentrations; and (vi) the ability of a multinodal network to capture the feedback relationships observed in vivo among GHRH, somatostatin, GH secretion, and GH and IGF-I negative feedback.
New analytical modalities for understanding dynamic regulation of the GH axis disclose a wide array of specific, prominent, and quantifiable gender differences in the physiological control mechanisms that direct this important neuroendocrine axis.
生长激素（GH）轴的神经内分泌调节受下丘脑信号、垂体内部机制及多级反馈控制的指导。因此，了解体内GH释放的生理性脉冲模式的调节是一项重大挑战。
介绍并综述几种旨在揭示GH轴生理调节新特征的新方法。为此，我强调了在脉冲式GH释放控制方面的性别差异，同时突出了揭示此类差异的新方法。
人类志愿者。
新的研究方法包括：（1）一种高灵敏度化学发光GH检测法，当与一种新的离散方差模型用于检测数据简化时，能够测量0.002微克/升的GH；（2）标准化线性回归技术，用于比较男性和女性的GH测量值；（3）应用所谓的反卷积分析，旨在从给定的血浆GH浓度曲线估计脉冲式激素（GH）分泌的潜在速率以及激素半衰期；（4）近似熵（ApEn）统计量，通过赋予一个单一非负数来量化激素释放的规律性或有序性，该非负数是数据中模式可重复性的一种度量；（5）网络模型的发展，以代表GH轴的生理连接和反馈活动。
上述新方法共同揭示了GH轴调节中显著的性别差异，包括：（i）女性的平均血清GH浓度较高，因为女性的GH分泌突发量比男性大；（ii）口服葡萄糖对GH的抑制作用相对降低，因为女性的GH分泌突发量比男性大，而GH分泌突发频率或血浆中GH半衰期无明显性别差异；（iv）与雄性相比，女性或雌性大鼠的GH释放过程中不规则或无序程度显著更高，表明雌性的模式可重复性明显降低；（v）与女性相比，男性对年龄和体脂百分比增加的负面影响以及体能对平均血清GH浓度的正面影响的敏感性大约高两倍；（vi）多节点网络能够捕捉体内观察到的生长激素释放激素（GHRH）、生长抑素、GH分泌以及GH和胰岛素样生长因子-I（IGF-I）负反馈之间的反馈关系。
用于理解GH轴动态调节的新分析方法揭示了在指导这一重要神经内分泌轴的生理控制机制中存在广泛的特定、显著且可量化的性别差异。
