title: Role of growth hormone-releasing hormone in sleep and growth impairments induced by upper airway obstruction in rats.
abstract: Upper airway obstruction (UAO) can lead to abnormal growth hormone (GH) homeostasis and growth retardation but the mechanisms are unclear. We explored the effect of UAO on hypothalamic GH-releasing hormone (GHRH), which has a role in both sleep and GH regulation. The tracheae of 22-day-old rats were narrowed; UAO and sham-operated animals were sacrificed 16 days post-surgery. To stimulate slow-wave sleep (SWS) and GH secretion, rats were treated with ritanserin (5-HT(2) receptor antagonist). Sleep was measured with a telemetric system. Hypothalamic GHRH, hypothalamic GHRH receptor (GHRHR) and GH receptor, and orexin were analysed using ELISA, real-time PCR and Western blot. UAO decreased hypothalamic GHRH, GHRHR and GH receptor levels, while orexin mRNA increased (p<0.01). In UAO rats, the duration of wakefulness was elevated and the duration of SWS, paradoxical sleep and slow-wave activity was reduced (p<0.001). Ritanserin alleviated these effects, i.e. normalised hypothalamic GHRH content, decreased wake duration, increased duration and depth of SWS, and attenuated growth impairment (p<0.001). Here, we present evidence that growth retardation in UAO is associated with a reduction in hypothalamic GHRH content. Our findings show that abnormalities in the GHRH/GH axis underlie both growth retardation and SWS-disorder UAO.
authors.affiliation: Department of Physiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 105, Beer-Sheva 84105, Israel. tarasiuk@bgu.ac.il
authors.forename: A
authors.initials: A
authors.lastname: Tarasiuk
authors.forename: N
authors.initials: N
authors.lastname: Berdugo-Boura
authors.forename: A
authors.initials: A
authors.lastname: Troib
authors.forename: Y
authors.initials: Y
authors.lastname: Segev
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006130:Growth Disorders / Q000378:metabolism / Q000503:physiopathology*; D013006:Growth Hormone / Q000097:blood; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics / Q000502:physiology*; D007031:Hypothalamus / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics; D008297:Male; D009479:Neuropeptides / Q000097:blood / Q000235:genetics; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics / Q000378:metabolism; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D020181:Sleep Apnea, Obstructive / Q000378:metabolism / Q000503:physiopathology*; D013686:Telemetry
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D012702:Serotonin Antagonists; D016713:Ritanserin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor