Effects of cortistatin-14 and somatostatin-14 on the endocrine response to hexarelin in humans

Cortistatin (CST)-14, a neuropeptide with high structural homology with somatostatine (SS)-14, binds all SS receptor subtypes but also shows activities not shared by SS. CST and SS are often co-expressed in the same neurons but are regulated by different stimuli. Moreover, CST, but not SS, also binds the GH secretagogue (GHS) receptor. We compared the effects of CST-14 and SS-14 (2.0 μg/kg/h iv from -30 to +90 min) on the endocrine response to hexarelin (HEX, 1.0 μg/kg iv at 0 min), a synthetic GHS, in 6 normal volunteers [age (mean±SEM): 28.7±2.9 yr; body mass index: 23.4±0.8 kg/m²]. GH, PRL, ACTH, cortisol, insulin and glucose levels were measured at each time point. CST-14 inhibited spontaneous GH secretion [Δ-areas under curves (-AUC): -83.57±44.8 vs 2.3±2.7 μg/l/h, p<0.01] to the same extent of SS-14 (-186.1±162.9 μg/l/h, p<0.01). CST-14 as well as SS-14 also inhibited insulin secretion (p<0.05). The GH response to HEX was similarly inhibited by either CST-14 (AUC: 3814.1±924.2 vs 1212.9±379.8 μg/l/h, p<0.05) or SS-14 (720.9±158.6 μg/l/h, p<0.05). HEX significantly increased PRL, ACTH and cortisol levels but these responses were not modified by either CST-14 or SS-14. The effects of CST-14 and SS-14 on insulin and glucose levels were not modified by HEX. In conclusion, this study shows that CST-14 inhibits the GH response to HEX to the same extent of SS-14. Like SS-14, CST-14 also inhibits insulin secretion but both do not modify the stimulatory effects of HEX on lactotroph and corticotroph secretion. Thus, CST-14 exerts full SS-14 activity in humans.