Cortistatin-17 and -14 exert the same endocrine activities as somatostatin in humans

Abstract Cortistatin (CST) is a neuropeptide, which binds with high affinity all somatostatin (SS) receptor subtypes and shows high structural homology with SS itself. A receptor specific for CST only, i.e., not recognized by SS, has been recently described in agreement with data reporting that not all CST actions are shared by SS. Interestingly, CST but not SS also binds ghrelin receptor (GHS-R1a) in vitro, suggesting a potential interplay between CST and ghrelin system. The aim of this study was to investigate in humans the endocrine and metabolic activities of human CST-17 in comparison with rat CST-14 that has previously been shown to exert the same endocrine actions of SS in healthy volunteers. To this aim, in six healthy male volunteers (age [median, 3rd–97th centiles]: 28.5; 23.6–34.3 years; Body Mass Index: 23.5; 21.0–25.1 kg/m 2 ), we studied the effects of human CST-17 (2.0 μg/kg/h iv over 120 min), rat CST-14 (2.0 μg/kg/h iv over 120 min) and SS-14 (2.0 μg/kg/h iv over 120 min) on: (a) spontaneous GH, ACTH, PRL, cortisol, insulin and glucose levels; (b) the GH responses to GHRH (1.0 μg/kg iv at 0 min); (c) the GH, PRL, ACTH, cortisol, insulin and glucose responses to ghrelin (1.0 μg/kg iv at 0 min). CST-17 inhibited ( p p p p p p p p p p