Broglio F, Benso A, Gottero C, Prodam F, Gauna C, Filtri L, Arvat E, van der Lely A J, Deghenghi R, Ghigo E
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy.
J Endocrinol Invest. 2003 Mar;26(3):192-6. doi: 10.1007/BF03345156.
Ghrelin, a 28-amino acid peptide predominantly produced by the stomach, displays strong GH-releasing activity mediated by the GH secretagogue (GHS)-receptor (GHS-R) type 1a at the hypothalamus-pituitary level. Ghrelin and synthetic GHS also possess other GH-independent peripheral endocrine and non-endocrine activities via the activation of peripheral GHS-R subtypes. In rats in vivo non-acylated ghrelin has been reported devoid of any endocrine activity; however, in vitro, it has been shown as effective as ghrelin in exerting anti-proliferative activity on tumor cell lines. The aim of the present study was to clarify whether non-acylated human ghrelin shares some of the endocrine activities of its acylated form in humans. To this goal, the effects of acylated or non-acylated ghrelin (1.0 microg/kg i.v. at 0 min) on GH, PRL, ACTH, F, insulin and glucose levels were studied in two different testing sessions in 7 normal young volunteers (age [mean +/- SE]: 24.3 +/- 1.7 yr; BMI: 21.5 +/- 0.9 kg/m2). The effects of placebo administration were also studied. The administration of acylated ghrelin induced prompt and marked increase in circulating GH levels (AUC: 5452.4 +/- 904.9 microgmin/l; p < 0.01 vs placebo) and significant increase in PRL (1273.5 +/- 199.7 microgmin/l; p < 0.01 vs placebo), ACTH (4482.7 +/- 954.4 pgmin/ml; p < 0.01 vs placebo) and F levels (15985.0 +/- 1141.9 microgmin/l; p < 0.01 vs placebo). Its administration was also followed by decrease in insulin levels (1448.67 +/- 137.9 mUmin/l; p < 0.05 vs placebo) that was coupled with an increase in plasma glucose levels (10974.2 +/- 852.5 mgmin/dl; p < 0.05 vs placebo). The administration of non-acylated ghrelin and that of placebo did not induce any change in the hormonal parameters or in glucose levels. In conclusion, this study shows that in humans nonacylated ghrelin does not possess the pituitaric and pancreatic endocrine activities of human ghrelin octanoylated in Serine 3.
胃饥饿素是一种主要由胃产生的含28个氨基酸的肽，在下丘脑 - 垂体水平通过1a型生长激素促分泌素（GHS）受体（GHS - R）介导，具有强大的生长激素释放活性。胃饥饿素和合成的GHS还可通过激活外周GHS - R亚型，产生其他不依赖生长激素的外周内分泌和非内分泌活性。在大鼠体内，未酰化的胃饥饿素已被报道没有任何内分泌活性；然而，在体外实验中，它在对肿瘤细胞系发挥抗增殖活性方面已被证明与胃饥饿素一样有效。本研究的目的是阐明未酰化的人胃饥饿素是否具有与酰化形式相同的某些内分泌活性。为了实现这一目标，在7名正常年轻志愿者（年龄[平均值±标准误]：24.3±1.7岁；体重指数：21.5±0.9kg/m²）的两个不同测试阶段中，研究了酰化或未酰化胃饥饿素（0分钟时静脉注射1.0μg/kg）对生长激素、催乳素、促肾上腺皮质激素、皮质醇、胰岛素和葡萄糖水平的影响。同时也研究了给予安慰剂的效果。给予酰化胃饥饿素后，循环生长激素水平迅速显著升高（曲线下面积：5452.4±904.9μg·min/l；与安慰剂相比，p<0.01），催乳素（1273.5±199.7μg·min/l；与安慰剂相比，p<0.01）、促肾上腺皮质激素（4482.7±954.4pg·min/ml；与安慰剂相比，p<0.01）和皮质醇水平（15985.0±1141.9μg·min/l；与安慰剂相比，p<0.01）也显著升高。给予酰化胃饥饿素后，胰岛素水平下降（1448.67±137.9mU·min/l；与安慰剂相比，p<0.05），同时血糖水平升高（10974.2±852.5mg·min/dl；与安慰剂相比，p<0.05）。给予未酰化胃饥饿素和安慰剂后，激素参数和血糖水平均未发生任何变化。总之，本研究表明，在人类中，未酰化的胃饥饿素不具有丝氨酸3位辛酰化的人胃饥饿素的垂体和胰腺内分泌活性。
