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 microg/kg/h i.v. from -30 to +90 min) on the endocrine response to hexarelin (HEX, 1.0 microg/kg i.v. 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 [delta-areas under curves (-AUC): -83.57+/-44.8 vs 2.3+/-2.7 microg/l/h, p<0.01] to the same extent of SS-14 (-186.1+/-162.9 microg/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 microg/l/h, p<0.05) or SS-14 (720.9+/-158.6 microg/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.
Benso
A
A
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy.
Gottero
C
C
Prodam
F
F
Gauna
C
C
Destefanis
S
S
Filtri
L
L
van der Lely
A J
AJ
Deghenghi
R
R
Ghigo
E
E
Broglio
F
F
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D004702:Endocrine Glands / Q000187:drug effects* / Q000378:metabolism*; D006728:Hormones / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology*
D001786:Blood Glucose; D006728:Hormones; D009479:Neuropeptides; D009842:Oligopeptides; D010456:Peptides, Cyclic; C467796:cortistatin 14; C086184:hexarelin; D013004:Somatostatin