Central injection of urocortin-3 but not corticotrophin-releasing hormone influences the ghrelin/GHS-R1a system of the proventriculus and brain in chicks

Ghrelin, the endogenous ligand for growth hormone secretagogue receptor 1a (GHS-R1a), stimulates food intake in mammals centrally and peripherally. In contrast, central injection of ghrelin inhibits feeding in neonatal chicks (Gallus gallus), which is thought to be mediated by the corticotrophin-releasing hormone (CRH) system, indicating that the mechanisms underlying ghrelin's action are different in chicks and mammals. However, the interaction between the ghrelin system and the CRH system has not been fully clarified in chicks. In the present study, we examined the effect of intracerebroventricular (ICV) injection of CRH and urocortin-3 (UCN-3), a CRH family peptide and an endogenous ligand for the CRH type-2 receptor (CRH-R2), on synthesis and secretion of ghrelin in chicks. Intracerebroventricular injection of UCN-3 but not CRH increased plasma ghrelin concentration (P < 0.05), diencephalic mRNA expression of ghrelin, and GHS-R1a (P < 0.05) and tended to decrease ghrelin (P = 0.08) and GHS-R1a (P = 0.10) mRNA expression in the proventriculus. Moreover, ICV injection of UCN-3 tended to increase diencephalic mRNA expression of CRH-R2 (P = 0.08) and CRH had no effect on it. In addition, ICV injection of CRH but not UCN-3 increased plasma corticosterone concentration (P < 0.05) and decreased the diencephalic mRNA expression of CRH-R1 (P < 0.05). These results clearly indicate that the roles of the CRH system for the ghrelin system are divided. The present study suggests that UCN-3 is mainly involved in the ghrelin system in chicks perhaps through the CRH-R2.