A number of studies have demonstrated effects of GHRH on sleep quality and it has been suggested that GH secretion and sleep may share common regulatory mechanisms (98). In rodents, intracerebral as well as systemic injections of GHRH stimulate non-REM sleep, even in hypophysectomized animals (99-102). Systemic injections of GHRH also stimulate REM sleep in intact, but not in hypophysectomized rodents (101,102). Conversely, inhibition of endogenous GHRH using GHRH antagonists or antibodies to GHRH decreases both non-REM sleep and GH secretion (98,103) .Inhumans, discrepant data have been reported. No effects of GHRH on visually scored sleep stages were found when the peptide was injected during daytime or before sleep onset (104,105), or when it was given as an infusion (97,106). However, delta power during the first 100 min of sleep was significantly enhanced following bedtime injection of GHRH (105). When the intravenous injections were performed during sleep, stimulatory effects on the duration of stages III and IV (106-108) and modest increases in REM sleep (106,108) were observed in normal young subjects. Similar—though weaker—effects were reported in healthy elderly controls (109). Sleep-promoting effects of the peptide may depend on the timing of administration (108,110). The persistence of stimulatory effects of GHRH on non-REM sleep in hypophysectomized rodents indicates that these effects are not mediated by GH (101,102). In contrast, the finding that increases in REM sleep following GHRH administration are seen only in intact animals suggests that REM-enhancing effects of GHRH may be mediated by GH (101,102). This hypothesis is consistent with the effects of exogenous GH administration on human sleep, which, as indicated above, have been mostly in the direction of a stimulation of REM, rather than non-REM, sleep.
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