http://repub.eur.nl/res/aut/43532/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/29370/ 2008-02-01T00:00:00Z Cortistatin (CST), a neuropeptide with high structural homology with somatostatin (SST), binds all SST receptor (SST-R) subtypes but, unlike SST, also shows high binding affinity to ghrelin receptor (GHS-R1a). CST exerts the same endocrine activities of SST in humans, suggesting that the activation of the SST-R might mask the potential interaction with ghrelin system. CST-8, a synthetic CST-analogue devoid of any binding affinity to SST-R but capable to bind the GHS-R1a, has been reported able to exert antagonistic effects on ghrelin actions either in vitro or in vivo in animals. We studied the effects of CST-8 (2.0 μg/kg iv as a bolus or 2.0 μg/kg/h iv as infusion) on both spontaneous and ghrelin- or hexarelin- (1.0 μg/kg iv as bolus) stimulated GH, PRL, ACTH and cortisol secretion in 6 normal volunteers. During saline, no change occurred in GH and PRL levels while a spontaneous ACTH and cortisol decrease was observed. As expected, both ghrelin and hexarelin stimulated GH, PRL, ACTH and cortisol secretion (p < 0.05). CST-8, administered either as bolus or as continuous infusion, did not modify both spontaneous and ghrelin- or hexarelin-stimulated GH, PRL, ACTH and cortisol secretion. In conclusion, CST-8 seems devoid of any modulatory action on either spontaneous or ghrelin-stimulated somatotroph, lactotroph and corticotroph secretion in humans in vivo. These negative results do not per se exclude that, even at these doses, CST-8 might have some neuroendocrine effects after prolonged treatment or that, at higher doses, may be able to effectively antagonize ghrelin action in humans. However, these data strongly suggest that CST-8 is not a promising candidate as GHS-R1a antagonist for human studies to explore the functional interaction between ghrelin and cortistatin systems. http://repub.eur.nl/res/pub/35854/ 2007-02-01T00:00:00Z 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.