Sleep-promoting effects of growth hormone-releasing hormone in normal men

Abstract

Growth hormone-releasing hormone (GHRH) promotes rapid-eye-movement (REM) and non-REM sleep in animals, but there is little direct evidence for a hypnogenic action of GHRH in humans. In the present study, the possible somnogenic effects of intravenous bolus injections of a dose of GHRH eliciting physiological elevations of GH secretion in healthy young men were investigated. GHRH (0.3 micrograms/kg body wt) was given in early sleep [i.e., 1st slow-wave (SW) period], late sleep (i.e., 3rd REM period), and early sleep after sleep deprivation until 0400 h (i.e., 1st SW period). In the absence of sleep deprivation, injection of GHRH in early sleep did not modify SW sleep but increased REM sleep. GHRH administration in the third REM period was followed by a marked decrease of wake and an almost 10-fold increase in SW sleep. When GHRH was administered during the first SW period after sleep deprivation until 0400 h, the duration of wake decreased. Thus GHRH has sleep-promoting effects in young adults, particularly when given at a time of decreased sleep propensity.

Ghrelin Stimulates Appetite, Imagination of Food, GH, ACTH, and Cortisol, but does not Affect Leptin in Normal Controls

“…Subsequently, he had a large meal (Weikel et al, 2003). This observation fits with various studies from our laboratory and others showing that repetitive (Steiger and Holsboer, 1997;Weikel et al, 2003) and single (Kerkhofs et al, 1993;Antonijevic et al, 1999a) i.v. bolus injections of neuropeptides modulate human behavior, and in the latter experiments, modulate sleep.…”

The Somatostatin Analogue Octreotide Impairs Sleep and Decreases EEG Sigma Power in Young Male Subjects

“…Our finding in humans is at variance with the increase of SWA, which followed the suppression of NREMS after octreotide in the rat (Beranek et al, 1997(Beranek et al, , 1999. The decrease of stage 4 sleep after octreotide is in contrast to the increase of SWS after GHRH in humans (Kerkhofs et al, 1993;Marshall et al, 1996;Steiger et al, 1992) and of NREMS in laboratory animals (Obál et al, 1988Ehlers et al, 1986;Nistico et al, 1987;Zhang et al, 1999) and after ghrelin in humans (Weikel et al, 2003) and in mice (Obál et al, 2003). We showed previously that the timing of GHRH administration is a crucial issue.…”

“…These findings suggest that SRIF inhibits REMS in humans, either by decreasing the amount of rapid eye movements in young subjects or by decreasing the time spent in REMS in the elderly. This observation points again to a GHRH antagonistic action of SRIF, since GHRH increased, besides NREMS and also REMS, in some (Kerkhofs et al, 1993;Marshall et al, 1996) but not all studies (Steiger et al, 1992) in humans and in rats . In contrast, Danguir and co-workers reported increases of REMS after i.c.v.…”

“…Similarly, SWS increased after i.v. GHRH in young normal male subjects (Steiger et al, 1992;Kerkhofs et al, 1993;Marshall et al, 1996) and NREMS increased in a large group of healthy and depressed male subjects of a wide age range, whereas sleep was impaired after i.v. GHRH in female subjects (Antonijevic et al, 2000a, b).…”

Blockade of endogenous growth hormone-releasing hormone receptors dissociates nocturnal growth hormone secretion and slow-wave sleep

“…Meal times were standardized and caffeine and napping were prohibited. Data from studies investigating the effect of GHRH upon SWS (13,17) were used to perform power analysis. Assuming that the magnitude of the supposed decline in the percentage of SWS during GHRH antagonist infusion would be similar to the reported increase in SWS during GHRH administration, we would need 4 -12 subjects per group to have an 80% power to document this effect at 5% statistical level.…”