Sleep in mice with nonfunctional growth hormone-releasing hormone receptors.
The role of the somatotropic axis in sleep regulation was studied by using the lit/lit mouse with nonfunctional growth hormone (GH)-releasing hormone (GHRH) receptors (GHRH-Rs) and control heterozygous C57BL/6J mice, which have a normal phenotype. During the light period, the lit/lit mice displayed significantly less spontaneous rapid eye movement sleep (REMS) and non-REMS (NREMS) than the controls. Intraperitoneal injection of GHRH (50 microg/kg) failed to promote sleep in the lit/lit mice, whereas it enhanced NREMS in the heterozygous mice. Subcutaneous infusion of GH replacement stimulated weight gain, increased the concentration of plasma insulin-like growth factor-1 (IGF-1), and normalized REMS, but failed to restore normal NREMS in the lit/lit mice. The NREMS response to a 4-h sleep deprivation was attenuated in the lit/lit mice. In control mice, intraperitoneal injection of ghrelin (400 microg/kg) elicited GH secretion and promoted NREMS, and intraperitoneal administration of the somatostatin analog octretotide (Oct, 200 microg/kg) inhibited sleep. In contrast, these responses were missing in the lit/lit mice. The results suggest that GH promotes REMS whereas GHRH stimulates NREMS via central GHRH-Rs and that GHRH is involved in the mediation of the sleep effects of ghrelin and somatostatin.
Obal
Ferenc
F
Department of Physiology and Endocrine Unit, University of Szeged, A. Szent-Györgyi Medical Center, 6720 Szeged, Hungary.
Alt
Jeremiah
J
Taishi
Ping
P
Gardi
Janos
J
Krueger
James M
JM
D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D017353:Gene Deletion; D054439:Ghrelin; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology; D036361:Peptide Hormones / Q000008:administration & dosage / Q000494:pharmacology; D010641:Phenotype; D018013:Receptors, Neuropeptide / Q000235:genetics* / Q000502:physiology; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics* / Q000502:physiology; D012890:Sleep / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D054439:Ghrelin; D036361:Peptide Hormones; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor; D015282:Octreotide