d-Lys-GHRP-6 does not modify the endocrine response to acylated ghrelin or hexarelin in humans

Benso, A.; Prodam, F.; Lucatello, B.; Gramaglia, E.; Riganti, F.; Schneider, H.; van der Lely, A.J.; Muccioli, G.; Ghigo, E.; Broglio, F.

doi:10.1016/j.npep.2006.10.001

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Volume 41, Issue 1 , Pages 45-49, February 2007

d-Lys-GHRP-6 does not modify the endocrine response to acylated ghrelin or hexarelin in humans

A. Benso
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
- First co-authorship.
F. Prodam
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
- First co-authorship.
B. Lucatello
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
E. Gramaglia
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
F. Riganti
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
H. Schneider
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
A.J. van der Lely
- Division of Endocrinology, Department of Internal Medicine, Erasmus University Rotterdam, Rotterdam, The Netherlands
G. Muccioli
- Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Turin, Italy
E. Ghigo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
F. Broglio
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy
- Corresponding author. Tel.: +39 0116334317; fax: +39 011 6647421.

Received 17 August 2006; accepted 3 October 2006. published online 18 November 2006.

Abstract

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 (2.0μg/kg iv as bolus or 2.0μg/kg/h iv as infusion) on both spontaneous and acylated ghrelin- or hexarelin (1.0μg/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/m²). The effects of d-Lys-GHRP-6 (2.0μg/kg iv as bolus+4.0μg/kg/h iv) on the GH response to 0.25μg/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 0.25μg/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.