Nocturnal ghrelin, ACTH, GH and cortisol secretion after sleep deprivation in humans.

Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor. It is hypothesised to play a key role in energy balance stimulating food intake and body weight. Besides GH-releasing hormone (GHRH) and somatostatin, it is thought to be a regulating factor of GH release. Ghrelin also appears to be involved in sleep regulation. We showed recently that ghrelin promotes slow-wave sleep and the nocturnal release of GH, cortisol and prolactin in humans. Similarly, promotion of non-rapid-eye-movement (NREM) sleep was reported in mice after systemic ghrelin. If ghrelin is a factor that induces and/or maintains sleep, it should be enhanced after a period of sleep deprivation (SD). To clarify this issue, nocturnal ghrelin, GH, ACTH and cortisol plasma concentrations were determined and simultaneously sleep electroencephalogram (EEG) was recorded (2300-0700 h) during sleep before and after 1 night of total SD in 8 healthy subjects. Compared to baseline, ghrelin levels increased earlier by a non-significant trend, already before the beginning of recovery sleep. Further a non-significant trend occurred, suggesting higher ghrelin secretion in the first half of the night. The ghrelin maximum was found significantly earlier after SD than at baseline. GH secretion during the first half of the night and total night after SD were elevated. ACTH and cortisol were also elevated, which was most pronounced during the second half of the night. No effects of SD on the time of the maximum were found for GH, ACTH and cortisol. The increase in ACTH after SD is a novel finding. Whereas the effects of SD on ghrelin levels were relatively weak, our findings are in line with the hypothesis that ghrelin is a sleep-promoting factor in humans. Ghrelin may be involved in sleep promotion after SD.

Ghrelin promotes slow-wave sleep in humans.

Ghrelin, an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor, stimulates GH release, appetite, and weight gain in humans and rodents. Synthetic GHSs modulate sleep electroencephalogram (EEG) and nocturnal hormone secretion. We studied the effect of 4 x 50 microg of ghrelin administered hourly as intravenous boluses between 2200 and 0100 on sleep EEG and the secretion of plasma GH, ACTH, cortisol, prolactin, and leptin in humans (n = 7). After ghrelin administration, slow-wave sleep was increased during the total night and accumulated delta-wave activity was enhanced during the second half of the night. Rapid-eye-movement (REM) sleep was reduced during the second third of the night, whereas all other sleep EEG variables remained unchanged. Furthermore, GH and prolactin plasma levels were enhanced throughout the night, and cortisol levels increased during the first part of the night (2200-0300). The response of GH to ghrelin was most distinct after the first injection and lowest after the fourth injection. In contrast, cortisol showed an inverse pattern of response. Leptin levels did not differ between groups. Our data show a distinct action of exogenous ghrelin on sleep EEG and nocturnal hormone secretion. We suggest that ghrelin is an endogenous sleep-promoting factor. This role appears to be complementary to the already described effects of the peptide in the regulation of energy balance. Furthermore, ghrelin appears to be a common stimulus of the somatotropic and hypothalamo-pituitary-adrenocortical systems. It appears that ghrelin is a sleep-promoting factor in humans.