精氨酸和吡啶斯的明对生长激素释放激素诱导的肥胖症和库欣综合征患者生长激素升高的影响。

Effect of arginine and pyridostigmine on the GHRH-induced GH rise in obesity and Cushing's syndrome.

作者信息

Procopio M, Invitti C, Maccario M, Grottoli S, Cavagnini F, Camanni F, Ghigo E

机构信息

Department of Clinical Pathophysiology, University of Turin, Torino, Italy.

出版信息

Int J Obes Relat Metab Disord. 1995 Feb;19(2):108-12.

PMID:7735336

Abstract

OBJECTIVES

The aim of this work was to clarify the mechanisms underlying growth hormone (GH) hyposecretion in Cushing's syndrome (CS) and in obesity. We studied the GH response to GH-releasing hormone (GHRH) alone and combined with arginine or pyridostigmine, two substances likely to inhibit hypothalamic somatostatin release.

DESIGN

Three tests with GHRH alone (1 microgram/kg i.v. at 0 min) and combined with arginine (ARG, 0.5 g/kg infused over 30 min) or pyridostigmine (PD, 120 mg orally at -60 min) were performed 3 days apart and in random order in eight women with CS (five with ACTH-dependent and three with ACTH-independent hypercortisolism, age 18-56, BMI 26.1 +/- 1.5 Kg/m2) and 11 with OB (age 17-54, BMI 42.9 +/- 2.2 Kg/m2). Eleven normal women (age 23-50, BMI 21.9 +/- 0.3 Kg/m2) were studied as controls (C).

MEASUREMENTS

Serum GH and IGF-I levels were measured by radioimmunoassay. The GH secretory responses were expressed either as absolute values (micrograms/L) or as areas under the curve (AUC, micrograms/L/h) calculated by trapezoidal integration. IGF-I concentrations were expressed as absolute values (micrograms/L) with reference to a pure recombinant IGF-I preparation.

RESULTS

Basal GH levels in CS were similar to those registered in OB (mean +/- s.e.m. 0.7 +/- 0.1 vs 0.9 +/- 0.2 microgram/L) and lower than in C (3.4 +/- 0.5 microgram/L, P < 0.00001). On the other hand, IGF-I levels were similar in all groups. The GHRH-induced GH rise in CS was lower, though not significantly, to that observed in OB (AUC: 65.6 +/- 13.2 vs 192.5 +/- 61.7 microgram/L/h) and both GH responses were significantly lower than that of C (1029.9 +/- 98.0 micrograms/L/h, P < 0.00001). ARG enhanced the GHRH-induced GH release in CS (331.9 +/- 51.9 micrograms/L/h vs GHRH alone, P < 0.0001), OB (852.4 +/- 162.1 micrograms/L/h, P < 0.0001) and C (3362.6 +/- 386.0 micrograms/L/h, P < 0.0002). However, the GH response to GHRH plus ARG in CS was lower (P < 0.002) than that in OB which, in turn, was lower than that in C (P < 0.00001). Pyridostigmine significantly enhanced the GHRH-induced GH rise in C (2808.5 +/- 221.2 micrograms/L/h, P < 0.00001) and, to a lesser extent, in OB (627.3 +/- 84.7 micrograms/L/h, P < 0.0002) but not in CS (102.9 +/- 25.0 micrograms/L/h).

CONCLUSIONS

Our results indicate that the GH releasable pool is reduced in obesity and, to an even greater extent, in Cushing's syndrome. The inability of pyridostigmine and arginine to restore a normal GH response to GHRH in these conditions makes the existence of a hypothalamic somatostatinergic hyperactivity unlikely.

摘要

目的

本研究旨在阐明库欣综合征（CS）和肥胖症中生长激素（GH）分泌不足的潜在机制。我们研究了GH对单独使用生长激素释放激素（GHRH）以及联合使用精氨酸或新斯的明的反应，这两种物质可能抑制下丘脑生长抑素的释放。

设计

对8名CS女性（5名促肾上腺皮质激素依赖型和3名促肾上腺皮质激素非依赖型高皮质醇血症患者，年龄18 - 56岁，体重指数26.1±1.5 Kg/m²）和11名肥胖（OB）女性（年龄17 - 54岁，体重指数42.9±2.2 Kg/m²）进行了三项试验，分别为单独使用GHRH（0分钟时静脉注射1μg/kg）以及联合使用精氨酸（ARG，30分钟内静脉输注0.5 g/kg）或新斯的明（PD，-60分钟时口服120 mg），三项试验间隔3天进行，顺序随机。选取11名正常女性（年龄23 - 50岁，体重指数21.9±0.3 Kg/m²）作为对照（C）。

测量

采用放射免疫分析法测定血清GH和IGF - I水平。GH分泌反应以绝对值（μg/L）或通过梯形积分计算的曲线下面积（AUC，μg/L/h）表示。IGF - I浓度以相对于纯重组IGF - I制剂的绝对值（μg/L）表示。

结果

CS患者的基础GH水平与OB患者相似（均值±标准误 0.7±0.1 vs 0.9±0.2μg/L），低于C组（3.4±0.5μg/L，P < 0.00001）。另一方面，所有组的IGF - I水平相似。CS患者中GHRH诱导的GH升高低于OB患者（虽无显著差异，AUC：65.6±13.2 vs 192.5±61.7μg/L/h），且两种GH反应均显著低于C组（1029.9±98.0μg/L/h，P < 0.00001）。精氨酸增强了CS患者（331.9±51.9μg/L/h vs 单独使用GHRH，P < 0.0001）、OB患者（852.4±162.1μg/L/h，P < 0.0001）和C组（3362.6±386.0μg/L/h，P < 0.0002）中GHRH诱导的GH释放。然而，CS患者中GHRH加精氨酸后的GH反应低于OB患者（P < 0.002），而OB患者又低于C组（P < 0.00001）。新斯的明显著增强了C组（2808.5±221.2μg/L/h，P < 0.00001）中GHRH诱导的GH升高，在OB患者中也有一定程度增强（627.3±84.7μg/L/h，P < 0.0002），但在CS患者中无明显增强（102.9±25.0μg/L/h）。