Endogenous ghrelin regulates episodic GH secretion by amplifying GH pulse amplitude: Evidence from antagonism of the GHS-R1a receptor

Abstract

Ghrelin was purified from rat stomach as an endogenous ligand for the growth hormone secretagogue (GHS) receptor. As a GHS, ghrelin stimulates GH release, but it also has additional activities, including stimulation of appetite and weight gain. Plasma GH and ghrelin secretory patterns appear unrelated whereas many studies have correlated ghrelin variations with food intake episodes. In order to evaluate the role of endogenous ghrelin, GH secretion and food intake were monitored in male rats infused subcutaneously (6 μ g/h during 10 h) or intracerebroventrically (5 μ g/h during 48 h) with BIM-28163, a full competitive antagonist of the GHS-R1a receptor. Subcutaneous BIM-28163 infusion significantly decreased GH area under the curve during a 6 hour sampling period by 54% and peak amplitude by 46%. Twelve hours after the end of treatment these parameters returned to normal. Central treatment was similarly effective [-37% and 42% for AUC and -44% and 49% for peak amplitude on the first and second days of infusion, respectively]. Neither peripheral nor central BIM-28163 injection modifies GH peak number, GH nadir or IGF-1 levels. In this protocol, food intake is not strongly modified and water intake is unchanged. Subcutaneously infusion of BIM-28163 did not change plasma leptin and insulin levels evaluated at 12:00 h and 16:00 h. On the contrary, central BIM-28163 infusion slightly increased leptin and significantly increased insulin concentrations. Thus, endogenous ghrelin, through GHS-R1a, acts as a strong endogenous amplifier of spontaneous GH peak amplitude. The mechanisms by which ghrelin modifies food intake remain to be defined, and may involve a novel GHS receptor. Copyright © 2005 by The Endocrine Society.