Effects of sleep deprivation on ghrelin, ACTH, GH and cortisol secretion in normal controls

Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor. Besides GH-releasing hormone (GHRH) and somatostatin it is thought to be a regulating factor of GH release. Ghrelin 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-REM-sleep was reported in mice after systemic ghrelin. There are no data available about the pattern of ghrelin secretion during the recovery night after total sleep deprivation (TSD). Nocturnal ghrelin, GH, ACTH and cortisol plasma concentrations were determined by radioimmunoassay and simultaneously sleep EEG was recorded (23:00–07:00) during sleep before and after one night of TSD in 8 healthy subjects (3 females and 5 males, mean age 26.3yrs, SD 4.4). We observed a trend suggesting higher ghrelin secretion during the first half of the night after TSD (before TSD mean 466ng/ml, SD 113ng/ml, after TSD mean 545ng/ml, SD 176, p=0.093). In the night before TSD the maximum time of ghrelin secretion occured at 03:40 (SD 117min.) and after TSD this time point was 00:42 (SD 76min.), indicating an earlier ghrelin secretion after TSD (p<0.05). GH secretion during the first half of the night and total night after TSD were elevated. ACTH and cortisol were also elevated, which was most pronounced during the second half of the night (ACTH: AUC before TSD, mean 5278, SD 1814, after TSD mean 10817, SD 3314, p<0.05).

Since the ghrelin maximum occurred advanced and ghrelin levels increased by trend our view is supported that ghrelin is a sleep promoting factor in humans. GH and HPA hormones were elevated after TSD. To our knowledge the increase of ACTH after TSD is a novel finding. This is in line with our hypothesis that ghrelin acts as an interface of the hypothalamo-pituitary- adrenocortical (HPA) and hypothalamo-pituitary-somatotrophic (HPS) systems. However, it remains to be clarified whether the changes of GH, ACTH and cortisol are dependent on the increase of ghrelin.