Muruais C, Cordido F, Morales M J, Casanueva F F, Diéguez C
Department of Medicine, Hospital General Galicia, Santiago de Compostela, Spain.
Clin Endocrinol (Oxf). 1991 Dec;35(6):485-90. doi: 10.1111/j.1365-2265.1991.tb00932.x.
In normal subjects, corticosteroids stimulate growth hormone (GH) secretion at 3 hours. Obesity is associated with blunted GH secretion. In order to clarify both the deranged mechanism of GH secretion in obesity and the corticosteroid mechanism of action we have assessed in normal and obese subjects the effects of dexamethasone, pyridostigmine (a drug capable of suppressing somatostatin release) and GHRH. We also compared in normal subjects the stimulatory effect of three different corticosteroids on plasma GH levels.
In both normal and obese subjects the following tests were carried out: placebo; dexamethasone alone (4 mg i.v. at 0 minutes); and dexamethasone plus pyridostigmine (120 mg p.o. at 60 minutes). In normal subjects we also studied the effects of hydrocortisone (100 mg i.v. at 0 minutes) and deflazacort (a corticosteroid that does not cross the blood-brain barrier) (60 mg i.v. at 0 minutes). In obese subjects we also assessed the effect of dexamethasone plus GHRH (100 micrograms i.v. at 150 minutes) on plasma GH levels.
Ten normal subjects and 22 obese subjects were studied. Normal controls were within 10% of their ideal body weight. Obese subjects had a body mass index of 37.1 +/- 1.1 (mean +/- SEM).
Plasma GH levels were measured by radioimmunoassay.
Dexamethasone-induced GH secretion in normal subjects (28.6 +/- 7.8 millimicron/l, P less than 0.05). Corticosteroids did not alter GH levels in obese subjects. Pretreatment with pyridostigmine increased dexamethasone-induced GH release in normal subjects (40.8 +/- 6.8 millimicron/l) but this did not achieve statistical significance. Dexamethasone plus pyridostigmine did not alter GH levels in obese subjects (8.0 +/- 1.6 mU/l). In some subjects, dexamethasone pretreatment potentiated GHRH-stimulated GH secretion, while in half the subjects the basal GH levels were not altered. In control subjects, hydrocortisone and deflazacort caused GH release similar to dexamethasone.
Corticosteroids are a new and selective stimulus of GH secretion. They do not cause GH release in obese subjects. Their relative independence from cholinergic control suggest that they act by reducing somatostatin secretion.
在正常受试者中,皮质类固醇在3小时时刺激生长激素(GH)分泌。肥胖与GH分泌减弱有关。为了阐明肥胖中GH分泌紊乱的机制以及皮质类固醇的作用机制,我们在正常和肥胖受试者中评估了地塞米松、吡啶斯的明(一种能够抑制生长抑素释放的药物)和生长激素释放激素(GHRH)的作用。我们还在正常受试者中比较了三种不同皮质类固醇对血浆GH水平的刺激作用。
在正常和肥胖受试者中均进行了以下试验:安慰剂;单独使用地塞米松(0分钟时静脉注射4mg);地塞米松加吡啶斯的明(60分钟时口服120mg)。在正常受试者中,我们还研究了氢化可的松(0分钟时静脉注射100mg)和地夫可特(一种不能穿过血脑屏障的皮质类固醇)(0分钟时静脉注射60mg)的作用。在肥胖受试者中,我们还评估了地塞米松加GHRH(150分钟时静脉注射100μg)对血浆GH水平的影响。
研究了10名正常受试者和22名肥胖受试者。正常对照组体重在理想体重的10%以内。肥胖受试者的体重指数为37.1±1.1(均值±标准误)。
采用放射免疫分析法测量血浆GH水平。
地塞米松诱导正常受试者GH分泌(28.6±7.8毫微摩尔/升,P<0.05)。皮质类固醇未改变肥胖受试者的GH水平。吡啶斯的明预处理增加了地塞米松诱导的正常受试者GH释放(40.8±6.8毫微摩尔/升),但未达到统计学意义。地塞米松加吡啶斯的明未改变肥胖受试者的GH水平(8.0±1.6mU/升)。在一些受试者中,地塞米松预处理增强了GHRH刺激的GH分泌,而在一半受试者中,基础GH水平未改变。在对照受试者中,氢化可的松和地夫可特引起的GH释放与地塞米松相似。
皮质类固醇是GH分泌的一种新的选择性刺激物。它们不会引起肥胖受试者的GH释放。它们相对独立于胆碱能控制,提示它们通过减少生长抑素分泌发挥作用。