Hexarelin is a synthetic six‑amino‑acid peptide that makes the pituitary release a lot of growth hormone (GH). In healthy men it worked better than the natural GH‑releasing hormone (GHRH) and gave an even bigger GH spike when used together with GHRH. Somatostatin, which normally blocks GH, could almost completely stop GHRH‑induced GH but only reduced the effect of hexarelin.

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)