Modulation of growth hormone-releasing activity of hexarelin in man.
Hexarelin (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) is a new synthetic growth hormone (GH)-releasing hexapeptide. The mechanism of action of hexarelin in man is not fully elucidated. As for other GH-releasing peptides, an action on both the pituitary gland and the hypothalamus has been hypothesized. In the present study, we evaluated the modulation of GH-releasing activity of hexarelin in man. In a first experiment conducted on 6 healthy male volunteers, we studied the interaction of the maximally effective intravenous dose of hexarelin (2 micrograms/kg i.v.) with GH-releasing hormone (GHRH, 2 micrograms/kg i.v.) and somatostatin (2 micrograms/kg/h i.v.). In a second experiment involving another 6 male subjects, we evaluated the interaction of hexarelin with neuroactive substances, such as pirenzepine (0.6 mg/kg i.v.), pyridostigmine (120 mg p.o.) and arginine (0.5 g/kg i.v.), thought to modulate endogenous somatostatin secretion. Hexarelin induced a higher increase in GH levels as compared to GHRH (integrated output calculated as area under the curve AUC0-120 4,693 +/- 691 vs. 1,494 +/- 102 micrograms.min/l, p < 0.01). Coadministration of hexarelin and GHRH produced a higher GH response than hexarelin alone (AUC0-120 7,395 +/- 450 micrograms.min/l, p < 0.05). Somatostatin abolished the GH response to GHRH (AUC0-120 363 +/- 89 micrograms.min/l, p < 0.01), while it only blunted that to hexarelin (AUC0-120 1,314 +/- 297 micrograms.min/l, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Arvat
E
E
Department of Clinical Pathophysiology, University of Turin, Italy.
Gianotti
L
L
Di Vito
L
L
Imbimbo
B P
BP
Lenaerts
V
V
Deghenghi
R
R
Camanni
F
F
Ghigo
E
E
D000328:Adult; D000595:Amino Acid Sequence; D001120:Arginine / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology*; D010890:Pirenzepine / Q000494:pharmacology*; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology*
D009842:Oligopeptides; C086184:hexarelin; D010890:Pirenzepine; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine; D011729:Pyridostigmine Bromide