Somatostatin may play a role in the inhibition of growth hormone (GH) response to GH-releasing hormone (GHRH) in hypercortisolism. To examine this hypothesis we studied the effect of pyridostigmine, a cholinergic agonist that decreases hypothalamic somatostatin, on the GH response to GHRH in 8 controls, in 6 patients with endogenous hypercortisolism (3 with Cushing's disease and 3 with adrenal adenomas) and in 8 patients with exogenous hypercortisolism (lupus erythematosus chronically treated with 20-60 mg/day of prednisone). Each subject received GHRH(1-29)NH2,100 micrograms iv twice, preceded by pyridostigmine (120 mg) or placebo, orally. 2. The GH response to GHRH was significantly blunted in all hypercortisolemic patients compared to controls both after placebo (GH peak, 5.8 +/- 1.6 vs 46.2 +/- 15.9 micrograms/l, mean +/- SEM) and after pyridostigmine (15.7 +/- 5.6 vs 77.2 +/- 19.8 micrograms/l). 3. The GH response was absent in endogenous hypercortisolemic patients compared to the exogenous group, both after placebo (2.2 +/- 0.3 vs 8.5 +/- 2.4 micrograms/l) and after pyridostigmine (4.9 +/- 2.5 vs 23.8 +/- 8.7 micrograms/l). The GH release after GHRH/pyridostigmine for the exogenous group was similar to the response of controls treated with GHRH/placebo. 4. These results confirm that the GH response to GHRH is blunted in hypercortisolism, although more pronounced in the endogenous group. Pyridostigmine partially reversed this inhibition in the exogenous group. Therefore, somatostatin may play a role in the inhibition of GHRH-induced GH release in exogenous hypercortisolemic states.
摘要
生长抑素可能在高皮质醇血症中对生长激素释放激素（GHRH）刺激生长激素（GH）分泌的反应具有抑制作用。为验证这一假设，我们研究了吡啶斯的明（一种可降低下丘脑生长抑素水平的胆碱能激动剂）对8名对照者、6名内源性高皮质醇血症患者（3例库欣病患者和3例肾上腺腺瘤患者）以及8名外源性高皮质醇血症患者（长期接受20 - 60mg/天泼尼松治疗的红斑狼疮患者）GH对GHRH反应的影响。每位受试者静脉注射两次GHRH(1 - 29)NH2，每次100μg，注射前口服吡啶斯的明（120mg）或安慰剂。2. 与对照者相比，所有高皮质醇血症患者在服用安慰剂后（GH峰值，5.8±1.6 vs 46.2±15.9μg/L，均值±标准误）以及服用吡啶斯的明后（15.7±5.6 vs 77.2±19.8μg/L），GH对GHRH的反应均明显减弱。3. 与外源性高皮质醇血症患者相比，内源性高皮质醇血症患者在服用安慰剂后（2.2±0.3 vs 8.5±2.4μg/L）以及服用吡啶斯的明后（4.9±2.5 vs 23.8±8.7μg/L），均未出现GH反应。外源性高皮质醇血症组在GHRH/吡啶斯的明刺激后的GH释放与接受GHRH/安慰剂治疗的对照者反应相似。4. 这些结果证实，高皮质醇血症患者中GH对GHRH的反应减弱，尽管在内源性高皮质醇血症组中更为明显。吡啶斯的明在外源性高皮质醇血症组中部分逆转了这种抑制作用。因此，生长抑素可能在外源性高皮质醇血症状态下对GHRH诱导的GH释放具有抑制作用。
