The endocrine response to acute ghrelin administration is blunted in patients with anorexia nervosa, a ghrelin hypersecretory state
The endocrine response to acute ghrelin administration is blunted in patients with anorexia nervosa, a ghrelin hypersecretory state
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DOI：
10.1111/j.1365-2265.2004.02011.x
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发表时间：
2004-05-01
影响因子：
3.2
通讯作者：
Ghigo, E
中科院分区：
文献类型：
--
作者：
Broglio, F;Gianotti, L;Ghigo, E
目的Ghrelin是生长激素促分泌素（GH secretagogue，GHS）受体（GHS-R）的天然配体，具有强烈刺激GH分泌的作用，同时还具有其他神经内分泌作用，刺激摄食，调节胰腺内分泌和能量平衡。Ghrelin的分泌受食物摄入的负调节。类似地，葡萄糖和胰岛素可能对生长素释放肽分泌产生抑制作用。饥饿素水平在肥胖症中降低，在神经性厌食症中升高，并通过体重恢复而恢复。厌食症患者循环胃饥饿素水平的慢性升高提示了这种情况下胃饥饿素促食欲作用的敏感性改变的假设。本研究的目的是确定ghrelin在神经性厌食症患者中的内分泌作用。设计我们招募了9名限制型神经性厌食症女性[AN;年龄（平均值+/-SEM）24.2 +/-1.8岁;体重指数（BMI）14.7 +/-0.4 kg/m2]和7名处于卵泡早期的正常年轻女性作为对照组（NW;年龄30.6 +/-3.1岁; BMI 20.3 +/-0.5kg/m2）。测量在所有受试者中，我们研究了GH、PRL、ACTH、皮质醇、胰岛素和葡萄糖对急性胃饥饿素给药（1.0 μ g/kg，静脉推注）的反应。GH对GHRH的反应所有受试者的基础ghrelin和IGF-I水平也进行了评估。结果AN患者的基础早晨ghrelin和GH水平（分别为643.6 +/-21.3 ng/l和10.4 +/-0.5 mug/l）高于（P <0.05）NW（分别为233.5 +/-14.2 ng/l和0.7 +/-0.7 mug/l）。然而，AN的IGF-I水平（145.3 +/-10.9 mug/l）低于NW（325.4 +/-12.6 mug/l）（P <0.05）。AN组GH对GHRH的反应高于NW组（P <0.05），而AN组GH对Ghrelin的反应低于NW组（P <0.05）。在AN和NW中，Ghrelin也引起PRL、ACTH和皮质醇水平的类似增加（P <0.05）。Ghrelin给药后，NW中的葡萄糖水平显著增加（P <0.05），但AN中没有。结论本研究表明，神经性厌食症，Ghrelin高分泌的临床条件，显示了特定的GH反应减少ghrelin，尽管高反应GHRH管理。神经性厌食症中生长激素对生长激素释放肽的反应受损，这与以前合成生长激素促分泌素对生长激素反应迟钝的证据一致，并可能反映了这种病理状态下生长激素释放肽水平慢性升高诱导的GHS受体脱敏。
OBJECTIVE Ghrelin, a gastric-derived natural ligand of the GH secretagogue (GHS)-receptor (GHS-R), strongly stimulates GH secretion but also possesses other neuroendocrine actions, stimulates food intake and modulates the endocrine pancreas and energy homeostasis. Ghrelin secretion is negatively modulated by food intake. Similarly, glucose and also insulin probably exert an inhibitory effect on ghrelin secretion. Fasting ghrelin levels are reduced in obesity, elevated in anorexia nervosa and restored by weight recovery. The chronic elevation of circulating ghrelin levels in anorexia suggested the hypothesis of an alteration of the sensitivity to the orexigenic action of ghrelin in this condition. The aim of this study was to define the endocrine actions of ghrelin in patients with anorexia nervosa.DESIGN We enrolled nine women with anorexia nervosa of restricter type [AN; age (mean +/- SEM) 24.2 +/- 1.8 years; body mass index (BMI) 14.7 +/- 0.4 kg/m(2)] and seven normal young women in their early follicular phase as control group (NW; age 30.6 +/- 3.1 years; BMI 20.3 +/- 0.5 kg/m(2)).MEASUREMENTS In all the subjects we studied the GH, PRL, ACTH, cortisol, insulin and glucose responses to acute ghrelin administration (1.0 mug/kg as i.v. bolus). The GH response to GHRH (1.0 mug/kg as i.v. bolus) and basal ghrelin and IGF-I levels were also evaluated in all the subjects.RESULTS Basal morning ghrelin and GH levels in AN (643.6 +/- 21.3 ng/l and 10.4 +/- 0.5 mug/l, respectively) were higher (P < 0.05) than in NW (233.5 +/- 14.2 ng/l and 0.7 +/- 0.7 mug/l, respectively). However, IGF-I levels in AN (145.3 +/- 10.9 mug/l) were lower (P < 0.05) than in NW (325.4 +/- 12.6 mug/l). The GH response to GHRH in AN was higher (P < 0.05) than that in NW, but in AN the GH response to ghrelin was lower (P < 0.05) than that in NW. In AN and NW ghrelin also induced similar increases (P < 0.05) in PRL, ACTH and cortisol levels. Ghrelin administration was followed by significant increase in glucose levels in NW (P < 0.05) but not in AN.CONCLUSIONS This study demonstrates that anorexia nervosa, a clinical condition of ghrelin hypersecretion, shows a specific reduction in the GH response to ghrelin, despite the hyper-responsiveness to GHRH administration. The impaired GH response to ghrelin in anorexia nervosa agrees with previous evidence of blunted GH response to synthetic GH secretagogues and could reflect desensitization of the GHS receptor induced by the chronic elevation of ghrelin levels in this pathological state.