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 (2.0 μg/kg iv as bolus or 2.0 μg/kg/h iv as infusion) on both spontaneous and acylated ghrelin- or hexarelin (1.0 μg/kg iv as bolus) -stimulated GH, PRL, ACTH and cortisol levels were studied in six normal volunteers (age [mean ± SEM]: 25.4 ± 1.2 yr; BMI: 22.3 ± 1.0 kg/m2). The effects of d-Lys-GHRP-6 (2.0 μg/kg iv as bolus + 4.0 μg/kg/h iv) on the GH response to 0.25 μg/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 0.25 μg/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.

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Keywords ACTH, Acylated ghrelin, Cortisol, GH, GHSR1a antagonists, Hexarelin, PRL, d-Lys-GHRP-6
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Journal Neuropeptides (Edinburgh)
Benso, A, Prodam, F, Lucatello, B, Gramaglia, E, Riganti, F, Schneider, H, … Broglio, F. (2007). d-Lys-GHRP-6 does not modify the endocrine response to acylated ghrelin or hexarelin in humans. Neuropeptides (Edinburgh), 41(1), 45–49. doi:10.1016/j.npep.2006.10.001