Cordido F, Casanueva F F, Dieguez C
Hospital Xeral Lugo, Endocrine Unit, Spain.
J Clin Endocrinol Metab. 1989 Feb;68(2):290-3. doi: 10.1210/jcem-68-2-290.
GH secretion in response to provocative stimuli is decreased in obese individuals. However, the precise mechanism causing this decrease is unknown. In an attempt to determine if reduced cholinergic stimulation accounts for the decreased GH secretion, we studied the effect of enhanced cholinergic tone induced by pyridostigmine on GHRH-stimulated GH secretion in a group of seven obese and seven normal subjects. When GHRH (100 micrograms, iv) was administered after placebo in the obese group, mean plasma GH rose from 0.5 +/- (0.1 (+/- SE) to 3.6 +/- 1.5 micrograms/L at 30 min. When the same obese subjects were given GHRH 60 min after pyridostigmine administration (120 mg, orally), the mean plasma GH level rose from 1.8 +/- 0.6 to 21.0 +/- 7.5 micrograms/L at 30 min. The responses to placebo and pyridostigmine were significantly different at 15, 30, 45, 60, and 90 min. In the normal subjects, a similar dose of GHRH induced a GH peak of 24.3 +/- 7.1 micrograms/L, and the GHRH-stimulated peak was significantly higher (56.2 +/- 16.8 micrograms/L) after pyridostigmine administration. To study the effect of pyridostigmine alone six other obese and six other normal subjects were tested with pyridostigmine or placebo on different days. In the normal subjects the mean peak plasma GH level after pyridostigmine was 12.5 +/- 3.1 micrograms/L, and in the obese subjects it was 4.6 +/- 1.3 micrograms/L. Thus, pyridostigmine potentiated the action of GHRH, rather than merely being additive. We conclude that pyridostigmine stimulates GH secretion in obese as well as normal subjects, although the response was less in the former group. Pyridostigmine potentiates the response to GHRH in both groups, but again, the response was less in the obese subjects. These results suggest that the impaired somatotroph responsiveness in obese subjects may be due to chronically decreased hypothalamic cholinergic tone, resulting in enhanced somatostatinergic tone.
肥胖个体对刺激性刺激的生长激素（GH）分泌减少。然而，导致这种减少的确切机制尚不清楚。为了确定胆碱能刺激减少是否是GH分泌减少的原因，我们研究了吡啶斯的明诱导的胆碱能张力增强对一组7名肥胖和7名正常受试者中生长激素释放激素（GHRH）刺激的GH分泌的影响。在肥胖组中，安慰剂后静脉注射GHRH（100微克），30分钟时血浆GH均值从0.5±（0.1（±标准误））升至3.6±1.5微克/升。当相同的肥胖受试者在口服吡啶斯的明（120毫克）60分钟后给予GHRH时，30分钟时血浆GH均值从1.8±0.6升至21.0±7.5微克/升。在15、30、45、60和90分钟时，对安慰剂和吡啶斯的明的反应有显著差异。在正常受试者中，相似剂量的GHRH诱导的GH峰值为24.3±7.1微克/升，吡啶斯的明给药后GHRH刺激的峰值显著更高（56.2±16.8微克/升）。为了研究单独使用吡啶斯的明的效果，另外6名肥胖和6名正常受试者在不同日期用吡啶斯的明或安慰剂进行测试。在正常受试者中，吡啶斯的明后的血浆GH平均峰值水平为12.5±3.1微克/升，在肥胖受试者中为4.6±1.3微克/升。因此，吡啶斯的明增强了GHRH的作用，而不仅仅是相加作用。我们得出结论，吡啶斯的明刺激肥胖和正常受试者的GH分泌，尽管前一组的反应较小。吡啶斯的明在两组中均增强了对GHRH的反应，但同样，肥胖受试者的反应较小。这些结果表明，肥胖受试者中生长激素细胞反应性受损可能是由于下丘脑胆碱能张力长期降低，导致生长抑素能张力增强。
