Kluge Michael, Schüssler Petra, Bleninger Philipp, Kleyer Sara, Uhr Manfred, Weikel Jutta C, Yassouridis Alexander, Zuber Verena, Steiger Axel
Max-Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany.
Psychoneuroendocrinology. 2008 May;33(4):497-506. doi: 10.1016/j.psyneuen.2008.01.008. Epub 2008 Mar 10.
Ghrelin 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 01:00h, 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+/-3.9min) compared to placebo (336.3+/-6.8min). REM sleep was decreased (B: 84.3+/-4.2 [p<0.1]; C: 74.2+/-7.0 [p<0.05]; D: 80.4+/-2.7min [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.
胃饥饿素可激活生长激素轴以及下丘脑 - 垂体 - 肾上腺轴，在睡眠调节中起关键作用。简单来说，生长激素释放激素（GHRH）可增加男性的慢波睡眠和快速眼动睡眠，而促肾上腺皮质激素释放激素（CRH）则增加清醒时间并减少快速眼动睡眠。胃饥饿素在睡眠调节中的作用，尤其是其与GHRH和CRH的相互作用尚不完全清楚。我们旨在阐明胃饥饿素、GHRH和CRH在睡眠调节以及皮质醇和生长激素分泌方面的相互作用。在这项单盲、随机、交叉研究中，对10名健康男性（25.7±3.0岁）在22:00、23:00、00:00和01:00四个时间点分别给予安慰剂（A）、胃饥饿素（B）、胃饥饿素和GHRH（C）或胃饥饿素和CRH（D），并测定夜间生长激素和皮质醇分泌以及多导睡眠图。与安慰剂（336.3±6.8分钟）相比，在所有真实给药条件下非快速眼动睡眠均显著增加（p<0.05）（平均值±标准误：B组：355.3±7.4；C组：365.4±8.1；D组：371.4±3.9分钟）。与安慰剂（100.9±8.3）相比，快速眼动睡眠减少（B组：84.3±4.2 [p<0.1]；C组：74.2±7.0 [p<0.05]；D组：80.4±2.7分钟 [p<0.05]）。CRH加胃饥饿素减少了清醒时间并提高了睡眠效率；此外，与其他治疗条件相比，快速眼动睡眠潜伏期缩短。CRH增强了胃饥饿素诱导的皮质醇分泌，但对生长激素分泌无相关影响。反过来，GHRH增强了胃饥饿素诱导的生长激素分泌，但对皮质醇分泌无影响。总之，胃饥饿素表现出独特的睡眠效应，GHRH和CRH均倾向于增强这种效应。与单独使用CRH在先前研究中的作用相反，CRH与胃饥饿素共同给药时具有改善睡眠和允许快速眼动睡眠的作用。
