Endocrine activities of cortistatin-14 and its interaction with GHRH and ghrelin in humans.
Cortistatin (CST)-14, a neuropeptide with high homology with somatostatin (SS)-14, binds all sst subtypes but, unlike SS, also ghrelin's receptor. In six normal adults, we studied the effects of CST-14 or SS-14 administration (2.0 micro g/kg/h iv) on: 1) GH and insulin secretion; 2) the GH response to GHRH (1.0 microg/kg i.v.); and 3) the GH, prolactin (PRL), ACTH, cortisol, insulin, and glucose responses to ghrelin (1.0 microg/kg i.v.). CST-14 inhibited GH and insulin secretion (P < 0.01) to the same extent of SS-14. The GH response to GHRH was similarly inhibited (P < 0.01) by either CST-14 or SS-14. Ghrelin released more GH than GHRH (P < 0.01); these responses were similarly inhibited (P < 0.05) by either CST-14 or SS-14, that made ghrelin-induced GH rise similar to that after GHRH alone. Neither CST-14 nor SS-14 modified PRL, ACTH, or cortisol responses to ghrelin. The inhibitory effect of CST-14 and SS-14 on insulin was unaffected by ghrelin that, in turn, reduced insulin secretion per se (P < 0.01). Ghrelin increased glucose levels (P < 0.05); CST-14 and SS-14 did not modify this effect. Thus, CST-14 inhibits both basal and stimulated GH secretion in humans to the same extent of SS-14. The GH-releasing activity of ghrelin seems partially resistant to CST-14 as well as SS-14. CST-14 and SS-14 do not affect PRL and ACTH secretion but, like ghrelin, inhibit insulin secretion; the ghrelin-induced inhibition is not additive with that of CST-14 or SS-14, suggesting a common mechanism of action on beta cell secretion.
Broglio
Fabio
F
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, 10126 Turin, Italy.
Arvat
Emanuela
E
Benso
Andrea
A
Gottero
Cristina
C
Prodam
Flavia
F
Grottoli
Silvia
S
Papotti
Mauro
M
Muccioli
Giampiero
G
van der Lely
Aart Jan
AJ
Deghenghi
Romano
R
Ghigo
Ezio
E
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001786:Blood Glucose; D004347:Drug Interactions; D054439:Ghrelin; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage* / Q000009:adverse effects; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage* / Q000378:metabolism; D036361:Peptide Hormones; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D011388:Prolactin / Q000097:blood; D013004:Somatostatin / Q000378:metabolism
D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D009479:Neuropeptides; D036361:Peptide Hormones; D010455:Peptides; C099323:cortistatin; D019382:Human Growth Hormone; D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013007:Growth Hormone-Releasing Hormone; D006854:Hydrocortisone