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Articles in PresS, published online ahead of print October 3, 2002
Am J Physiol Regu Physiol, 10.1152/ajpregu.00361.2002
Submitted on June 20, 2002
Accepted on September 20, 2002
1 Department of Physiology, University of Szeged, Szeged, Hungary; Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA, USA
2 Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA, USA
3 Endocrine Unit, University of Szeged, A. Szent-Gyorgyi Medical Center, Szeged, Hungary
* To whom correspondence should be addressed. E-mail: krueger{at}vetmed.wsu.edu.
The role of the somatotropic axis in sleep regulation was studied by using the lit/lit mouse with non-functional 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 (ip) injection of GHRH (50 µg/kg) failed to promote sleep in the lit/lit mice whereas it enhanced NREMS in the controls. 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, ip injection of ghrelin (400 µg/kg) elicited GH secretion and promoted NREMS, and ip administration of the somatostatin analog, octretotide (OCT, 200 µg/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.
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