d-Lys-GHRP-6 does not modify the endocrine response to acylated ghrelin or hexarelin in humans.
Acylated ghrelin exerts numerous endocrine and non-endocrine activities via the GH Secretagogue receptor type 1a (GHS-R1a). D-Lys-GHRP-6 has been widely studied in vitro and in vivo in animal studies as GHS-R1a antagonist; its action in humans has, however, never been tested so far. Aim of our study was to verify the antagonistic action of D-Lys-GHRP-6 on the endocrine responses to acylated ghrelin and hexarelin, a peptidyl synthetic GHS, in humans. The effects of different doses of D-Lys-GHRP-6 (2.0microg/kg iv as bolus or 2.0microg/kg/h iv as infusion) on both spontaneous and acylated ghrelin- or hexarelin (1.0microg/kg iv as bolus) -stimulated GH, PRL, ACTH and cortisol levels were studied in six normal volunteers (age [mean+/-SEM]: 25.4+/-1.2yr; BMI: 22.3+/-1.0kg/m(2)). The effects of D-Lys-GHRP-6 (2.0microg/kg iv as bolus+4.0microg/kg/h iv) on the GH response to 0.25microg/kg iv as bolus acylated ghrelin was also studied. During saline, spontaneous ACTH and cortisol decrease was observed while non changes occurred in GH and PRL levels. Acylated ghrelin and hexarelin stimulated (p<0.05) GH, PRL, ACTH and cortisol secretions. D-Lys-GHRP-6 administered either as bolus or a continuous infusion did not modify both spontaneous and acylated ghrelin- or hexarelin-stimulated GH, PRL, ACTH and cortisol secretion. D-Lys-GHRP-6 did not modify even the GH response to 0.25microg/kg iv acylated ghrelin. In conclusion, D-Lys-GHRP-6 does not affect the neuroendocrine response to both ghrelin and hexarelin. These findings question D-Lys-GHRP-6 as an effective GHS-R1a antagonist for human studies.
Benso
A
A
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy.
Prodam
F
F
Lucatello
B
B
Gramaglia
E
E
Riganti
F
F
Schneider
H
H
van der Lely
A J
AJ
Muccioli
G
G
Ghigo
E
E
Broglio
F
F
D000215:Acylation; D000324:Adrenocorticotropic Hormone / Q000097:blood* / Q000187:drug effects; D000328:Adult; D054439:Ghrelin; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000097:blood* / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007700:Kinetics; D008239:Lysine; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D036361:Peptide Hormones / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood* / Q000187:drug effects; D012016:Reference Values
D054439:Ghrelin; D009842:Oligopeptides; D036361:Peptide Hormones; C086184:hexarelin; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013007:Growth Hormone-Releasing Hormone; D008239:Lysine; D006854:Hydrocortisone