Ghigo E, Procopio M, Maccario M, Bellone J, Arvat E, Campana S, Boghen M F, Camanni F
Department of Clinical Pathophysiology, University of Turin, Italy.
Horm Metab Res. 1993 Jun;25(6):305-8. doi: 10.1055/s-2007-1002105.
Spontaneous GH secretion as well as GH response to several stimuli including GHRH have been shown to be reduced in obesity. To clarify the pathogenesis underlying these alterations, in six obese patients (3 males and 3 females, age 20-44 yrs, BMI = 42.1 +/- 2.2) on unrestricted diet we studied the effect of 8 day GHRH pretreatment (1 micrograms/kg iv each day) on the acute somatotropic response to the neurohormone administered both alone and combined with arginine (ARG, 0.5 g/kg iv infused from 0 to 30 min) which likely inhibits the release of hypothalamic somatostatin. Before treatment the GH response to GHRH (AUC: 231.9 +/- 106.4 micrograms/l/h) was potentiated (p < 0.001) by ARG (932.6 +/- 166.2 micrograms/l/h). However, the GH responses to the neurohormone both alone and combined with ARG were lower (p < 0.02 and 0.002, respectively) than in normals (712.4 +/- 111.6 and 2608.3 +/- 453.2 micrograms/l/h, respectively). After repetitive GHRH administration, in obese subjects baseline GH and IGF-I levels were unchanged. Also the GH responses to GHRH both alone (217.3 +/- 68.1 micrograms/l/h) and combined with ARG (756.3 +/- 202.9 micrograms/l/h) were not modified. In conclusion, our data demonstrate the failure of GHRH pretreatment to improve the somatotrope hyporesponsiveness to GHRH both alone and combined with ARG suggesting the existence of a somatotropic defect in obesity.
肥胖患者的自发性生长激素（GH）分泌以及GH对包括生长激素释放激素（GHRH）在内的多种刺激的反应均已显示降低。为了阐明这些改变背后的发病机制，我们对6名肥胖患者（3名男性和3名女性，年龄20 - 44岁，体重指数[BMI]=42.1±2.2）进行了研究，这些患者饮食不受限制。我们研究了连续8天给予GHRH预处理（每天静脉注射1微克/千克）对单独给予神经激素以及联合精氨酸（ARG，0.5克/千克静脉注射，0至30分钟输注完毕）后的急性生长激素反应的影响，精氨酸可能会抑制下丘脑生长抑素的释放。治疗前，ARG可增强（p<0.001）对GHRH的GH反应（曲线下面积[AUC]：231.9±106.4微克/升/小时）（932.6±166.2微克/升/小时）。然而，单独给予神经激素以及联合ARG后的GH反应均低于正常人（分别为712.4±111.6和2608.3±453.2微克/升/小时）（分别为p<0.02和0.002）。重复给予GHRH后，肥胖受试者的基础GH和胰岛素样生长因子I（IGF-I）水平未改变。单独给予GHRH（217.3±68.1微克/升/小时）以及联合ARG（756.3±202.9微克/升/小时）后的GH反应也未改变。总之，我们的数据表明，GHRH预处理未能改善单独给予GHRH以及联合ARG时生长激素细胞对GHRH的低反应性，提示肥胖存在生长激素缺陷。
