Deficiency of growth hormone-releasing hormone signaling is associated with sleep alterations in the dwarf rat.
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 the dw/dw rats. 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 the dw/dw rats, indicating deficits in the central GHRHergic transmission. Hypothalamic GHRH content in dw/dw rats was also less than that found in Lewis rats. The dw/dw rats 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 the dw/dw rat. As determined by fast Fourier analysis of the electroencephalogram (EEG), the sleep deprivation-induced enhancements in EEG slow-wave activity in the dw/dw rats 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 the dw/dw rat.
Obál
F
F
Department of Physiology, University of Szeged, Albert Szent-Györgyi Medical Center, 6720 Szeged, Hungary.
Fang
J
J
Taishi
P
P
Kacsóh
B
B
Gardi
J
J
Krueger
J M
JM
D000818:Animals; D002940:Circadian Rhythm; D004393:Dwarfism, Pituitary / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D004569:Electroencephalography; D013006:Growth Hormone / Q000172:deficiency; D013007:Growth Hormone-Releasing Hormone / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D011301:Preoptic Area / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011922:Rats, Mutant Strains; D018013:Receptors, Neuropeptide / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D012892:Sleep Deprivation; D020919:Sleep Disorders, Intrinsic / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D012894:Sleep Stages / Q000235:genetics
D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor