Deficiency of Growth Hormone-Releasing Hormone Signaling Is Associated with Sleep Alterations in the Dwarf Rat

• DOI: 10.1523/jneurosci.21-08-02912.2001
• Publication Date: 2018-04-13T22:26:59Z
• Authors: Ferenc Obál; Jidong Fang; Ping Taishi; Balint Kacsóh; Janos Gardi; James M. Krueger
• Keywords: Male; Receptors, Neuropeptide; Hypothalamus; 610; Growth Hormone-Releasing Hormone; Rats, Mutant Strains; 03 medical and health sciences; 0302 clinical medicine; Receptors, Pituitary Hormone-Regulating Hormone; 616; somatotropic axis; Animals; RNA, Messenger; sleep; ARTICLE; Dwarfism, Pituitary; dwarf; Reverse Transcriptase Polymerase Chain Reaction; Electroencephalography; sleep deprivation; GHRH receptor; Preoptic Area; Circadian Rhythm; Rats; rats; Sleep Disorders, Intrinsic; Rats, Inbred Lew; Growth Hormone; Pituitary Gland; Sleep Deprivation; Signal Transduction

The somatotropic axis, and particularly growth hormone-releasing hormone (GHRH), is implicated in the regulation of sleep–wake activity. To evaluate sleep in chronic somatotropic deficiency, sleep–wake activity was studied in dwarf (dw/dw) rats that are known to have a defective GHRH signaling mechanism in the pituitary and in normal Lewis rats, the parental strain of thedw/dwrats. In addition, expression of GHRH receptor (GHRH-R) mRNA in the hypothalamus/preoptic region and in the pituitary was also determined by means of reverse transcription-PCR, and GHRH content of the hypothalamus was measured. Hypothalamic/preoptic and pituitary GHRH-R mRNA levels were decreased in thedw/dwrats, indicating deficits in the central GHRHergic transmission. Hypothalamic GHRH content indw/dwrats was also less than that found in Lewis rats. Thedw/dwrats had less spontaneous nonrapid eye movement sleep (NREMS) (light and dark period) and rapid eye movement sleep (REMS) (light period) than did the control Lewis rats. After 4 hr of sleep deprivation, rebound increases in NREMS and REMS were normal in thedw/dwrat. As determined by fast Fourier analysis of the electroencephalogram (EEG), the sleep deprivation-induced enhancements in EEG slow-wave activity in thedw/dwrats were only one-half of the response in the Lewis rats. The results are compared with sleep findings previously obtained in GHRH-deficient transgenic mice. The alterations in NREMS are attributed to the defect in GHRH signaling, whereas the decreases in REMS might result from the growth hormone deficiency in thedw/dwrat.