Recent studies have indicated that the release of GH is also under the control of an as yet unidentified stimulatory pathway that may be activated by synthetic compounds such as the GH-releasing peptides (GHRPs) and their functional agonists (116,117). These compounds are thought to act as functional somatostatin antagonists (118). It is not known whether this second axis for GH stimulation is also involved in sleep regulation. Indeed, the findings of the only study that has examined the effects of injections of GHRP-6 around bedtime were an enhancement of the amount of stage II sleep without any other significant effect on either SW sleep or REM sleep (119). These data do not exclude the possibility that, as was previously shown for GHRH, GHRP may have a stimulatory effect on SW sleep when given during the later part of the night, at a time when SW sleep is not naturally abundant. However, a recent study indicates that, in contrast with GHRH, single injections of GHRP, at a dosage resulting in similar GH
elevations, have no stimulatory effects on SW sleep, even when given at a time when SW sleep is not predominant (120).
Recently, we have shown that 7-d oral treatment with MK-677, a functional agonist of GHRP acting via the GHRP receptor (121), is associated with an increase in both stage IV and REM in normal young men (122). This intriguing finding is difficult to interpret because plasma GH levels were not elevated at the time of the sleep study (although acutely MK-677 is a powerful GH secretagogue) but plasma IGF-1 levels were markedly increased. Multiple complex mechanisms could be involved in the chronic effects of MK-677 on sleep with dubious relevance to the effects of direct, acute, stimulation of the GHRP axis.
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