Ghrelin alone or co-administered with GHRH or CRH increases non-REM sleep and decreases REM sleep in young males

SummaryGhrelin activates the somatotropic and the hypothalamic–pituitary–adrenal axes, being crucially involved in sleep regulation. Simplified, growth hormone releasing hormone (GHRH) increases slow-wave sleep and REM sleep in males, whilst corticotropin-releasing hormone (CRH) increases wakefulness and decreases REM sleep. Ghrelin's role in sleep regulation and particularly its interactions with GHRH and CRH are not entirely clear. We aimed to elucidate the interactions between ghrelin, GHRH and CRH in sleep regulation and the secretion of cortisol and GH. Nocturnal GH and cortisol secretion and polysomnographies were determined in 10 healthy males (25.7±3.0 years) four times, receiving placebo (A), ghrelin (B), ghrelin and GHRH (C), or ghrelin and CRH (D) at 22:00, 23:00, 00:00, and 01:00 h, in this single-blind, randomized, cross-over study. Non-REM sleep was significantly (p<0.05) increased in all verum conditions (mean±SEM: B: 355.3±7.4; C: 365.4±8.1; D: 371.4±3.9 min) compared to placebo (336.3±6.8 min). REM sleep was decreased (B: 84.3±4.2 [p<0.1]; C: 74.2±7.0 [p<0.05]; D: 80.4±2.7 min [p<0.05]) compared to placebo (100.9±8.3). CRH+ghrelin decreased the time spent awake and enhanced the sleep efficiency; furthermore, the REM latency was decreased compared to the other treatment conditions. CRH enhanced the ghrelin-induced cortisol secretion but had no relevant effect on GH secretion. In turn, GHRH enhanced the ghrelin-induced GH secretion but had no effect on cortisol secretion. In conclusion, ghrelin exhibited distinct sleep effects, which tended to be enhanced by both GHRH and CRH. CRH had sleep-improving and REM permissive effects when co-administered with ghrelin, being in contrast to the effect of CRH alone in previous studies.