A low dose of ghrelin stimulates growth hormone (GH) release synergistically with GH-releasing hormone in humans

The synergistic relationship between GH-releasing secretagogue (GHS) and GH -releasing hormone (GHRH) with respect to GH secretion is well known, In th e present study, we report a similar relationship between GHRH and ghrelin, a recently identified endogenous ligand for the GHS receptor. In normal ma le adults, various doses of ghrelin were intravenously administered alone o r together with 1.0 mug/kg GHRH. At small doses of 0.08 and 0.2 mug/kg ghre lin, combined administration of the two peptides significantly stimulated G H release in a synergistic manner, the mean GH response values of the two p eptide combinations were more than the summed mean GH response values of ea ch peptide alone (P<0.05). In addition, at 1.0 <mu>g/kg ghrelin, the tenden cy of the synergistic effect was observed, although the comparison was not statistically significant probably due to a submaximal dose ceiling effect. No synergistic effects with respect to ACTH or prolactin secretion were ob served. In conclusion, the synergistic interaction between ghrelin and GHRH was clearly shown and might be useful for a provocation test to diagnose G H deficiency.