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 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 microg*min/l; p < 0.01 vs placebo) and significant increase in PRL (1273.5 +/- 199.7 microg*min/l; p < 0.01 vs placebo), ACTH (4482.7 +/- 954.4 pg*min/ml; p < 0.01 vs placebo) and F levels (15985.0 +/- 1141.9 microg*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 nonacylated ghrelin does not possess the pituitaric and pancreatic endocrine activities of human ghrelin octanoylated in Serine 3.