Cordido F, Dieguez C, Casanueva F F
Department of Medicine, Faculty of Medicine, Santiago University, Santiago de Campostela, Spain.
J Clin Endocrinol Metab. 1990 May;70(5):1361-70. doi: 10.1210/jcem-70-5-1361.
Obesity is associated with an impairment of the GH secretion elicited by all stimuli known to date, but the basic mechanism of this alteration is unknown. To determine whether obesity is associated with a chronic state of tonic somatostatin secretion, several tests with GH stimuli with or without pyridostigmine were undertaken in both obese subjects and matched controls. Pyridostigmine reduces somatostatin release from the hypothalamus by increasing central cholinergic neurotransmission. The administration of clonidine (300 micrograms, orally) to obese subjects did not modify basal GH values (1.9 +/- 0.7 micrograms/L at 90 min), while in control subjects the clonidine-induced GH peak was 13.1 +/- 1.6 micrograms/L. Pretreatment with pyridostigmine (120 mg, orally) notably increased clonidine-stimulated GH secretion in both the obese (6.9 +/- 1.8 micrograms/L) and control (17.6 +/- 2.7 micrograms/L) subjects. Since clonidine acts by releasing endogenous GHRH, similar studies were undertaken employing arginine, which presumably enhances GH release by reducing somatostatin discharge. Arginine administration in obese subjects induced an increase in GH levels of 5 +/- 2.3 micrograms/L, which was significantly smaller than that in the matched control subjects (13.3 +/- 2.4 micrograms/L). Pretreatment with pyridostigmine increased the arginine action toward a GH peak of 12.2 +/- 2.2 micrograms/L in the obese and 21.6 +/- 2.5 micrograms/L in control subjects. As a third hypothalamic stimulus of GH secretion, trials of insulin-induced hypoglycemia were carried out. Hypoglycemia induced an increase in GH levels in obese subjects of 12.2 +/- 1.8 micrograms/L, which was higher than that produced by any other stimulus, but lower than that in control subjects (28.4 +/- 5.5 micrograms/L). In contrast with the previous two GH stimuli, pretreatment with pyridostigmine did not modify the hypoglycemia-induced GH release in either obese or normal subjects. Our results lend support to the view that clonidine acts through GH-releasing hormone release and arginine by reducing somatostatin discharge from the hypothalamus. In addition, they seem to indicate that hypoglycemia acts by a combination of both mechanisms, mainly through a reduction in somatostatin release. These findings support the idea that obesity is associated with a state of chronic somatostatin hypersecretion as the basis for the derangements in GH secretion.
肥胖与迄今已知的所有刺激所引发的生长激素（GH）分泌受损有关，但这种改变的基本机制尚不清楚。为了确定肥胖是否与生长抑素的慢性持续性分泌状态有关，对肥胖受试者和匹配的对照组进行了多项使用或不使用吡啶斯的明的GH刺激试验。吡啶斯的明通过增加中枢胆碱能神经传递来减少下丘脑生长抑素的释放。给肥胖受试者口服可乐定（300微克）并未改变基础GH值（90分钟时为1.9±0.7微克/升），而在对照受试者中，可乐定诱导的GH峰值为13.1±1.6微克/升。口服吡啶斯的明（120毫克）预处理显著增加了肥胖受试者（6.9±1.8微克/升）和对照受试者（17.6±2.7微克/升）中可乐定刺激的GH分泌。由于可乐定通过释放内源性生长激素释放激素（GHRH）起作用，因此采用精氨酸进行了类似研究，精氨酸可能通过减少生长抑素释放来增强GH释放。给肥胖受试者注射精氨酸后，GH水平升高了5±2.3微克/升，明显低于匹配的对照受试者（13.3±2.4微克/升）。口服吡啶斯的明预处理增强了精氨酸的作用，使肥胖受试者的GH峰值达到12.2±2.2微克/升，对照受试者达到21.6±2.5微克/升。作为GH分泌的第三种下丘脑刺激，进行了胰岛素诱导的低血糖试验。低血糖使肥胖受试者的GH水平升高了12.2±1.8微克/升，高于任何其他刺激所产生的升高幅度，但低于对照受试者（28.4±5.5微克/升）。与前两种GH刺激不同，口服吡啶斯的明预处理并未改变肥胖或正常受试者中低血糖诱导的GH释放。我们的结果支持以下观点：可乐定通过释放生长激素释放激素起作用，精氨酸通过减少下丘脑生长抑素的释放起作用。此外，结果似乎表明低血糖通过两种机制的结合起作用，主要是通过减少生长抑素的释放。这些发现支持了这样一种观点，即肥胖与生长抑素慢性分泌过多状态有关，这是GH分泌紊乱的基础。
