Ultradian rhythmicity of ghrelin secretion in relation with GH, feeding behavior, and sleep-wake patterns in rats

Ghrelin, an endogenous ligand for the GHS receptor, stimulates GH secretion and gastrointestinal motility and has orexigenic effects. In this study, the relationships between ghrelin, GH secretion, feeding behavior, and sleep-wake patterns were investigated in adult male rats. The half-life of exogenous ghrelin (10 mug iv) in plasma was about 30 min. Repeated administration of ghrelin at 3- to 4-h intervals (one during lights-on and two during lights-off periods) increased GH release and feeding activity, and decreased rapid eye movement sleep duration. Endogenous plasma ghrelin levels exhibited pulsatile variations that were smaller and less regular compared with those of GH. No significant correlation between GH and ghrelin circulating levels was found, although mean interpeak intervals and pulse frequencies were close for the two hormones. In contrast, ghrelin pulse variations were correlated with food intake episodes in the lights off period, and plasma ghrelin concentrations decreased by 26% in the 20 min following the end of the food intake periods. A positive correlation between ghrelin levels and active wake was found during the first 3 h of the dark period only. In conclusion, ghrelin, in addition to affecting GH secretion, gastrointestinal motility, and feeding activity, also modifies sleep-wake patterns. However, a direct action of ghrelin per se or the indirect effects of feeding (and all of its attendant metabolic sequelae) on sleep cannot be differentiated. Moreover, ghrelin secretion is pulsatile and directly related to feeding behavior only.