Acute ghrelin response to intravenous dexamethasone administration in idiopathic short stature or isolated idiopathic growth hormone-deficient children

Abstract

Acylated ghrelin has been originally described for its potent GH-releasing activity mediated by the activation of the GH secretagogue receptor type 1a. More recently, ghrelin has been reported to exert several other GH-independent biological actions, among which in the modulation of metabolic functions. Glucocorticoids are well known to exert important metabolic functions but also to modulate GH secretion, although through mechanisms that have not been fully clarified so far. Interestingly, the existence of a feedback link between glucocorticoids and ghrelin system has already been reported. The aim of our study was to evaluate the acute GH and ghrelin responses to dexamethasone (DEX) administration in children with idiopathic short stature (ISS) or isolated idiopathic GH deficiency (GHD). Eight children with ISS (age: 9.5+/-1.2 yr) and 7 with GHD (12.1+/-1.4 yr) underwent iv DEX administration (0.3 mg/body surface area at 0 min). IGF-I, GH, and ghrelin levels were assayed at baseline and every 30 min from 120 up to 240 min after DEX. Compared to baseline levels DEX decreased ghrelin in ISS at 120 min and 240 min (p<0.04). On the other hand DEX did not modify ghrelin levels in GHD. After DEX, ghrelin was reduced in ISS compared to GHD (p<0.02). DEX increased GH in ISS but not in GHD (peak: 11.1+/-1.2 vs 7.6+/-0.9 microg/l). Basal, as well as after-DEX ghrelin levels negatively correlated with IGF-I in GHD (p<0.03) and with height SD score (HSDS) in ISS (p<0.02). Acute DEX administration is able to decrease ghrelin in ISS, but not in GHD children. Both basal and after-DEX ghrelin levels negatively correlate with IGF-I and HSDS. All these data suggest the existence of a feedback link among ghrelin, glucocorticoids and the GH/IGF-I axis.

Effect of Arginine Infusion on Ghrelin Secretion in Growth Hormone-Sufficient and GH-Deficient Children

“…The lack of modulation of ghrelin secretion with respect to baseline levels after a relatively prolonged GH therapy was hypothesized to be a consequence of a balance between reduction of adiposity and insulin resistance and increased circulating GH levels (38). Similarly, in some studies, ghrelin levels were similar in GHD and GHS children and adults at fasting (28, 39-43). These findings are consistent with our results that suggest that ghrelin does not modulate the quantity but mainly quality of GH secretion by modulating the GH pulse amplitude (40).…”

“…This effect of oral clonidine might be related to its direct gastric action since it is known to play a role in delaying gastric emptying, inhibiting gastric motility, and to a major extent, in all gastric secretion (37). Regulation of ghrelin secretion by clonidine or other molecules with respect to GH status suggests specific actions of some molecules, as observed on dexamethasone administration, and needs further evaluation (28). …”