Reichardt B, Schrader M, Mojto J, Mehltretter G, Müller O A, Schopohl J
Medizinische Klinik, Klinikum Innenstadt der Ludwig-Maximilians-Universität, Munich, Germany.
J Clin Endocrinol Metab. 1996 May;81(5):1994-8. doi: 10.1210/jcem.81.5.8626871.
Repeated injection of GHRH leads to a decrease in the GH response in normal subjects. Arginine (Arg) stimulates GH secretion by suppression of hypothalamic somatostatin. To confirm these findings, eight normal men were examined in a series of five settings: test 1 (GHRH/GHRH-TRH), 100 micrograms GHRH injected iv, followed by 100 micrograms GHRH, iv, after 120 min and 200 micrograms TRH, iv, after 150 min; test 2 (GHRH/Arg-TRH), like test 1, but instead of the second GHRH injection, a 30 g Arg infusion over 30 min; test 3 (GHRH/GHRH-Arg-TRH), like test 1, but additionally a 30 g Arg infusion after 120 min; test 4 (GHRH-Arg-TRH), iv GHRH and Arg infusion initially, followed by iv TRH after 30 min; and test 5 (TRH), 200 micrograms TRH, iv, at 0 min. For statistical evaluation, the area under the GH curve (AUC) from 0-120 min was compared with the AUC from 120-240 min. The GH response to the second administration of GHRH was significantly lower (P < 0.02) than the first increase [AUC, 0.5 +/- 0.01 min.mg/L (mean +/- SE) vs. 1.2 +/- 0.3]. No significant differences were found between the GH responses to either GHRH or Arg alone (AUC, 0.9 +/- 0.2 min.mg/L vs. 0.9 +/- 0.2). A larger GH increase (P < 0.02) was seen after GHRH-Arg compared to GHRH alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 1.2 +/- 0.3). The GH response (P < 0.02) to GHRH-Arg stimulation was lower after previous GHRH injection than after GHRH-Arg stimulation alone (AUC, 1.9 +/- 0.4 min.mg/L vs. 3.5 +/- 0.9). There was a statistically significant difference between the TRH-stimulated TSH response in test 4 compared to that in test 5. We could show that decreasing GH responses to repeated GHRH can be avoided by a combined stimulation with GHRH/Arg. These findings suggest that the decreased GH response to a second GHRH bolus may be partly due to an elevated hypothalamic somatostatin secretion, which can be suppressed by Arg. The lower GH response to GHRH-Arg stimulation after a previous GHRH bolus suggests, furthermore, that the readily available GH pool in the human pituitary may be limited.
对正常受试者反复注射生长激素释放激素（GHRH）会导致生长激素（GH）反应降低。精氨酸（Arg）通过抑制下丘脑生长抑素刺激GH分泌。为证实这些发现，对8名正常男性在一系列5种情况下进行了检查：试验1（GHRH/GHRH-促甲状腺激素释放激素（TRH）），静脉注射100微克GHRH，120分钟后静脉注射100微克GHRH，150分钟后静脉注射200微克TRH；试验2（GHRH/Arg-TRH），与试验1相同，但第二次GHRH注射改为在30分钟内输注30克Arg；试验3（GHRH/GHRH-Arg-TRH），与试验1相同，但在120分钟后额外输注30克Arg；试验4（GHRH-Arg-TRH），最初静脉注射GHRH和Arg，30分钟后静脉注射TRH；试验5（TRH），在0分钟时静脉注射200微克TRH。为进行统计学评估，比较了0至120分钟的GH曲线下面积（AUC）与120至240分钟的AUC。第二次给予GHRH后的GH反应显著低于第一次升高（P<0.02）[AUC，0.5±0.01分钟·毫克/升（平均值±标准误）对1.2±0.3]。单独给予GHRH或Arg后的GH反应之间未发现显著差异（AUC，0.9±0.2分钟·毫克/升对0.9±0.2）。与单独给予GHRH相比，GHRH-Arg后GH升高幅度更大（P<0.02）（AUC，1.9±0.4分钟·毫克/升对1.2±0.3）。先前注射GHRH后，GHRH-Arg刺激后的GH反应（P<0.02）低于单独GHRH-Arg刺激后（AUC，1.9±0.4分钟·毫克/升对3.5±0.9）。试验4中TRH刺激的促甲状腺激素（TSH）反应与试验5相比有统计学显著差异。我们可以证明，通过GHRH/Arg联合刺激可避免对反复GHRH的GH反应降低。这些发现表明，对第二次GHRH推注的GH反应降低可能部分归因于下丘脑生长抑素分泌升高，而Arg可抑制这种分泌。此外，先前给予GHRH推注后对GHRH-Arg刺激的GH反应较低表明，人垂体中易于利用的GH储备可能有限。
