Non-acylated ghrelin does not possess the pituitaric and pancreatic endocrine activity of acylated ghrelin in humans

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 mug/kg iv 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/m(2)). 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 mug*min/l; p<0.01 vs placebo) and significant increase in PRL (1273.5 +/- 199.7 mug*min/l; p<0.01 vs placebo), ACTH (4482.7 +/- 954.4 mug*min/ml; p<0.01 vs placebo) and F levels (1 5985.0 +/- 1141.9 mug*min/l; p<0.01 vs placebo). Its administration was also followed by decrease in insulin levels (1448.67+/-137.9 mU*min/l; p<0.05 vs placebo) that was coupled with an increase in plasma glucose levels (10974.2 +/- 852.5 mg*min/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 non- acylated ghrelin does not possess the pituitaric and pancreatic endocrine activities of human ghrelin octanoylated in Serine 3. ((C))2003, Editrice Kurtis.