Alprazolam, a benzodiazepine, blunts but does not abolish the ACTH and cortisol response to hexarelin, a GHRP, in obese patients.

S Grottoli, E Arvat, C Gauna, B Maccagno, J Ramunni, R Giordano, M Maccario, R Deghenghi, E Ghigo
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引用次数: 5

Abstract

GH secretagogues (GHS) act on specific receptors at the pituitary and hypothalamic level and possess potent GH-releasing activity but also stimulate prolactin (PRL), ACTH and cortisol (F) secretion. However, hyperactivity of the HPA axis in obesity has been reported. The objective of this study was to clarify the endocrine activity of GHS in obesity. In nine obese patients (obese OB), 9 F, age, (34.8 +/- 3.7 y, body mass index (BMI), 35.0 +/- 2.2 kg/m2; WHR, 0.9 +/- 0.02), 14 controls (normal subjects, NS), 14 F, 30.4 +/- 0.9 y, 20.0 +/- 0.4 kg/m2), we studied the ACTH, F and GH responses to hexarelin (HEX, 2.0 microg/kg), a peptidyl GHS, alone and preceded by alprazolam (ALP, 0.02 mg/kg), and a benzodiazepine which has an inhibitory effect on corticotroph secretion. The HEX-induced ACTH response in OB was higher than that in n.s., but this difference did not attain statistical significance. In n.s. the HEX-induced ACTH response was abolished by ALP (P < 0.03) which, however, only blunted that in OB (P < 0.02). The GH response to HEX in OB was lower (P < 0.02) than that in n.s.. ALP blunted the GH response to HEX in n.s. (P < 0.03) while it did not modify that in OB. The GABAergic activation by alprazolam abolishes the ACTH response to hexarelin in normal subjects, while it only blunts that in obese subjects. Moreover, alprazolam blunts the GH response to hexarelin in normal but not in obese subjects. Thus, obese patients show partial refractoriness to the inhibitory effect of alprazolam on both corticotroph and somatotroph function.

阿普唑仑是一种苯二氮卓类药物,在肥胖患者中,它能减弱但不能消除促肾上腺皮质激素和皮质醇对己卡瑞林(一种GHRP)的反应。
GH分泌剂(GHS)作用于垂体和下丘脑水平的特定受体,具有强大的GH释放活性,但也刺激催乳素(PRL)、ACTH和皮质醇(F)的分泌。然而,肥胖中HPA轴的过度活跃已经有报道。本研究的目的是阐明肥胖中GHS的内分泌活动。9例肥胖患者(肥胖OB), 9例F,年龄(34.8 +/- 3.7 y),体重指数(BMI) (35.0 +/- 2.2 kg/m2);WHR, 0.9 +/- 0.02), 14名对照组(正常受试者,NS), 14名F, 30.4 +/- 0.9 y, 20.0 +/- 0.4 kg/m2),我们研究了ACTH, F和GH对hexarelin (HEX, 2.0微克/kg),肽基GHS,单独和前用阿普唑仑(ALP, 0.02 mg/kg)和苯二氮卓类药物的反应,后者对促皮质激素分泌有抑制作用。hex诱导的ACTH反应OB组高于ns组,但差异无统计学意义。在n.s.中,hexx诱导的ACTH反应被ALP消除(P < 0.03),而在OB中仅减弱(P < 0.02)。OB组GH对HEX的反应低于对照组(P < 0.02)。ALP能减弱n - s组的GH对HEX的反应(P < 0.03),而对OB组没有影响。阿普唑仑激活的gaba能消除正常人对hexarelin的ACTH反应,而肥胖组只减弱ACTH对hexarelin的反应。此外,阿普唑仑在正常受试者中减弱生长激素对赫萨瑞林的反应,而在肥胖受试者中则没有。因此,肥胖患者对阿普唑仑对促皮质和促生长功能的抑制作用表现出部分难治性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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