title: Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers.
abstract: Ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor and some GHSs exert different effects on sleep electroencephalogram (EEG) and sleep-related hormone secretion in humans. Similar to GH-releasing hormone (GHRH) ghrelin promotes slow-wave sleep in humans, whereas GH-releasing peptide-6 (GHRP-6) enhances stage 2 nonrapid-eye movement sleep (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 sleep-endocrine activity and the immune system is unknown. We investigated simultaneously the sleep EEG and nocturnal profiles of GH, ACTH, cortisol, prolactin, leptin, tumor necrosis factor (TNF)-alpha, and soluble TNF-alpha receptors in seven young normal volunteers after repetitive administration of 4 x 50 microg hexarelin or placebo at 22.00, 23.00, 24.00 and 01.00 h. Following hexarelin, stage 4 sleep 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 prolactin 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 sleep 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.
authors.affiliation: Max Planck Institute of Psychiatry, D-80804 Munich, Germany.
authors.forename: Ralf-Michael
authors.initials: RM
authors.lastname: Frieboes
authors.forename: Irina A
authors.initials: IA
authors.lastname: Antonijevic
authors.forename: Katja
authors.initials: K
authors.lastname: Held
authors.forename: Harald
authors.initials: H
authors.lastname: Murck
authors.forename: Thomas
authors.initials: T
authors.lastname: Pollmächer
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.forename: Axel
authors.initials: A
authors.lastname: Steiger
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D000704:Analysis of Variance; D004569:Electroencephalography; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D009842:Oligopeptides / Q000502:physiology*; D036361:Peptide Hormones / Q000819:agonists / Q000502:physiology; D011388:Prolactin / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists; D054440:Receptors, Ghrelin; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012016:Reference Values; D012890:Sleep / Q000502:physiology*; D012894:Sleep Stages / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D054439:Ghrelin; D009842:Oligopeptides; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C086184:hexarelin; C041048:growth hormone releasing hexapeptide; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D006854:Hydrocortisone