Ghrelin drives GH secretion during fasting in man.
OBJECTIVE
In humans, fasting leads to elevated serum GH concentrations. Traditionally, changes in hypothalamic GH-releasing hormone and somatostatin release are considered as the main mechanisms that induce this elevated GH secretion during fasting. Ghrelin is an endogenous ligand of the GH secretagogue receptor and is synthesized in the stomach. As ghrelin administration in man stimulates GH release, while serum ghrelin concentrations are elevated during fasting in man, this increase in ghrelin levels might be another mechanism whereby fasting results in stimulation of GH release.


METHODS
In ten healthy non-obese males we performed a double-blind placebo-controlled crossover study comparing fasting with and fasting without GH receptor blockade. GH, ghrelin, insulin, glucose and free fatty acids were assessed.


RESULTS
While ghrelin levels do not vary considerably in the fed state, fasting rapidly induced a diurnal rhythm in ghrelin concentrations. These changes in serum ghrelin concentrations during fasting were followed by similar, profound changes in serum GH levels. The rapid development of a diurnal ghrelin rhythm could not be explained by changes in insulin, glucose, or free fatty acid levels. Compared with fasting without pegvisomant, fasting with pegvisomant did not change the ghrelin rhythm.


CONCLUSIONS
These data indicate that ghrelin is the main driving force behind the enhanced GH secretion during fasting.
Muller
Alex F
AF
Division of Endocrinology, Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands. amuller@diakhuis.nl
Lamberts
Steven W J
SW
Janssen
Joop A M J L
JA
Hofland
Leo J
LJ
Koetsveld
Peter Van
PV
Bidlingmaier
Martin
M
Strasburger
Christian J
CJ
Ghigo
Ezio
E
Van der Lely
Aart Jan
AJ
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005215:Fasting / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D054439:Ghrelin; D019382:Human Growth Hormone / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007700:Kinetics; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage; D036361:Peptide Hormones; D010455:Peptides / Q000097:blood / Q000502:physiology*; D010919:Placebos; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D007328:Insulin; D009842:Oligopeptides; D036361:Peptide Hormones; D010455:Peptides; D010919:Placebos; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; C041048:growth hormone releasing hexapeptide; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant