Jaffe C A, Turgeon D K, Friberg R D, Watkins P B, Barkan A L
Department of Internal Medicine, Department of Veterans Affairs Medical Center, Ann Arbor, Michigan, USA.
J Clin Endocrinol Metab. 1995 Nov;80(11):3321-6. doi: 10.1210/jcem.80.11.7593445.
Pulsatile GH secretion in humans is under the dual and opposing regulation of hypothalamic GHRH and SRIH. GH pulses result from acute GHRH secretory discharges, and their occurrence and amplitude are augmented at night. We hypothesized that normal adults have predictable circadian or ultradian patterns of SRIH secretion and that this rhythm modulates both spontaneous GH secretion and the GH response to GHRH in a similar manner. To test this hypothesis, we compared baseline GH concentration patterns with GH profiles during submaximal iv boluses of GHRH. Every 20 min blood sampling for plasma GH determination over a 24-h period was performed in seven middle-aged men on days 1 and 7. Each subject received a GHRH (0.33 microgram/kg) iv bolus every 2 h on days 2-7, during which the GH responses to the first two boluses were measured. Plasma insulin-like growth factor I (IGF-I) was measured at 0800 h on each day. [The subjects had GH response to every GHRH bolus] and the integrated GH concentration on day 7 was increased 4.3 +/- 0.6-fold over that in the baseline study on day 1. There was no acute or chronic desensitization to GHRH, and the pituitary remained equally responsive to the GHRH boluses despite a 2.6-fold increase in IGF-I by day 7. During this same time period, there was a 1.4-fold increase in IGF-binding protein 3. The subjects showed similar circadian patterns of GH secretion at baseline and during repetitive GHRH boluses, with a maxima on each day occurring during the early night-time hours. These data demonstrate that healthy men remain sensitive to the GH-releasing effects of submaximal bolus doses of GHRH despite significant increases in GH and IGF-I. The similarities between the GH concentration profiles during days 1 and 7 are consistent with the hypothesis that the ultradian pattern of GH secretion in humans is in part a product of hypothalamic GHRH discharges superimposed on more slowly changing SRIH secretion.
人类生长激素（GH）的脉冲式分泌受下丘脑生长激素释放激素（GHRH）和生长抑素（SRIH）的双重且相反的调节。GH脉冲源于GHRH的急性分泌释放，且其出现频率和幅度在夜间会增加。我们推测正常成年人具有可预测的SRIH分泌昼夜节律或超昼夜节律模式，并且这种节律以类似方式调节自发性GH分泌以及GH对GHRH的反应。为了验证这一假设，我们将基础GH浓度模式与次最大剂量静脉推注GHRH期间的GH谱进行了比较。在第1天和第7天，对7名中年男性进行了为期24小时的每20分钟一次的采血以测定血浆GH。在第2 - 7天，每位受试者每2小时接受一次GHRH（0.33微克/千克）静脉推注，在此期间测量对前两次推注的GH反应。每天08:00测定血浆胰岛素样生长因子I（IGF - I）。[受试者对每次GHRH推注均有GH反应]，并且第7天的GH浓度积分比第1天的基础研究增加了4.3±0.6倍。对GHRH没有急性或慢性脱敏现象，尽管到第7天IGF - I增加了2.6倍，但垂体对GHRH推注的反应仍然相同。在同一时期，IGF结合蛋白3增加了1.4倍。受试者在基础状态和重复GHRH推注期间显示出相似的GH分泌昼夜节律模式，每天的最大值出现在夜间早期。这些数据表明，尽管GH和IGF - I显著增加，但健康男性对次最大剂量推注GHRH的GH释放作用仍保持敏感。第1天和第7天的GH浓度谱相似，这与以下假设一致：人类GH分泌的超昼夜模式部分是下丘脑GHRH释放叠加在变化更缓慢的SRIH分泌之上的产物。
