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Articles in PresS, published online ahead of print October 15, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00184.2002
Submitted on May 6, 2002
Accepted on October 6, 2002
1 Department of Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
* To whom correspondence should be addressed. E-mail: steiger{at}mpipsykl.mpg.de.
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 µg ghrelin administered hourly as intravenous bolusses between 2200 and 0100 on sleep EEG and the secretion of plasma GH, adrenocorticotropic hormone, cortisol, prolactin, and leptin in humans (n=7). After ghrelin, 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 somatotrophic and the HPA system. It appears that ghrelin is a sleep promoting factor in humans.
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