Cordido F, Peñalva A, Dieguez C, Casanueva F F
Endocrine Section Hospital General de Galicia, Santiago de Compostela, Spain.
J Clin Endocrinol Metab. 1993 Apr;76(4):819-23. doi: 10.1210/jcem.76.4.8473389.
GH secretion in response to all provocative stimuli is decreased in patients with obesity. However, the precise mechanism causing this impairment in GH release is unknown. His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To gain further insight into disrupted GH secretion in obesity, GHRP-6 and GH-releasing hormone (GHRH) at a dose of 100 micrograms, i.v., were administered either alone or in combination in a group of 19 obese subjects. In a group of obese patients, GHRP-6 induced GH secretion, with a GH peak (mean +/- SEM) of 15.7 +/- 4.4 micrograms/L and an area under the curve (AUC) of 674 +/- 187, which were larger than those after GHRH stimulation (6.8 +/- 1.1 and 412 +/- 71, respectively). Enhancement of the endogenous cholinergic tone was obtained in another group of obese subjects by means of pyridostigmine (120 mg, orally). Pyridostigmine administered 60 min before GHRP-6, increased both the mean GH peak (32.2 +/- 6.9) and the AUC (1413 +/- 537) after GHRP-6 administration. In a separate group of subjects, the combined administration of GHRP-6 and GHRH induced a massive discharge of GH, with individual responses ranging from 14-86 micrograms/L. GHRP-6 plus GHRH induced a mean GH peak of 42.2 +/- 10.9 and an AUC of 1894 +/- 784 (P < 0.05), clearly indicating a potentiating (synergic) action when the two compounds were administered together. These data show that GH responses to GHRP-6 were almost twice those to GHRH in obese patients. The stimulatory effect exerted by pyridostigmine on GHRP-6-induced GH secretion supported the view of increased somatostatinergic tone in obesity. Finally, the massive GH discharge that followed the administration of GHRH plus GHRP-6 was not observed after any stimulus in obesity, clearly indicating that the impaired GH secretion is a functional and potentially reversible state.
肥胖患者对所有刺激物的生长激素（GH）分泌均减少。然而，导致GH释放受损的确切机制尚不清楚。组氨酸-色氨酸-丙氨酸-色氨酸-苯丙氨酸-赖氨酸-氨基（GHRP-6）是一种合成化合物，它能在包括人类在内的多种物种中以剂量相关且特异的方式释放GH。为了进一步了解肥胖患者GH分泌的紊乱情况，对19名肥胖受试者静脉注射100微克剂量的GHRP-6和生长激素释放激素（GHRH），单独给药或联合给药。在一组肥胖患者中，GHRP-6诱导了GH分泌，GH峰值（平均值±标准误）为15.7±4.4微克/升，曲线下面积（AUC）为674±187，均大于GHRH刺激后的数值（分别为6.8±1.1和412±71）。另一组肥胖受试者通过口服吡啶斯的明（120毫克）增强内源性胆碱能张力。在GHRP-6给药前60分钟给予吡啶斯的明，可增加GHRP-6给药后的平均GH峰值（32.2±6.9）和AUC（1413±537）。在另一组受试者中，联合给予GHRP-6和GHRH可诱导大量GH释放，个体反应范围为14 - 86微克/升。GHRP-6加GHRH诱导的平均GH峰值为42.2±10.9，AUC为1894±784（P < 0.05），清楚地表明两种化合物一起给药时具有增强（协同）作用。这些数据表明，肥胖患者对GHRP-6的GH反应几乎是对GHRH反应的两倍。吡啶斯的明对GHRP-6诱导的GH分泌的刺激作用支持了肥胖患者生长抑素能张力增加的观点。最后，肥胖患者在任何刺激后均未观察到GHRH加GHRP-6给药后出现的大量GH释放，这清楚地表明GH分泌受损是一种功能性且可能可逆的状态。
