Hexarelin decreases slow-wave steep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers

Ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor and some GHSs exert different effects on steep electroencephalogram (EEG) and sleep-related hormone secretion in humans. Similar to GH-releasing hormone (GHRH) ghrelin promotes stow-wave steep in humans, whereas GH-releasing peptide-6 (GHRP-6) enhances stage 2 nonrapid-eye movement steep (NREMS). As GHRP-6, hexarelin is a synthetic GHS. Hexarelin is superior to GHRH and GHRP-6 in stimulating GH release. The influence of hexarelin on steep-endocrine activity and the immune system is unknown. We investigated simultaneously the steep EEG and nocturnal profiles of GH, ACTH, cortisol, protactin, leptin, tumor necrosis factor (TNF)-alpha, and soluble TNF-alpha receptors in seven young normal volunteers after repetitive administration of 4 x 50 mug hexarelin or placebo at 22.00, 23.00, 24.00 and 01.00 h. Following hexarelin, stage 4 steep during the first half of the night, and EEG delta power during the total night decreased significantly. Significant increases of the concentrations of GH and protactin during the total night, and of ACTH and of cortisol during the first half of the night were found. Leptin levels, TNF-alpha and soluble TNF receptors remained unchanged. We hypothesize that steep is impaired after hexarelin since the GHRH/corticotropin-releasing hormone (CRH) ratio is changed in favour of CRH. There are no hints for an interaction of hexarelin and the immune system. (C) 2003 Elsevier Ltd. All rights reserved.