Six-week treatment with hexarelin in young dogs: evaluation of the GH responsiveness to acute hexarelin or GHRH administration, and of the orexigeniceffect of hexarelin

In this study we evaluated, in six young (5-7 year-old) beagle dogs, the ef fects of a 6-week administration of hexarelin (250 mu g/kg s.c. twice daily ) on the GH response to an acute challenge with hexarelin or GHRH (2 mu g/k g i.v.), delivered before and after 3 and 6 weeks of treatment. The GH peak response to acute hexarelin or GHRH: initially increased, with a maximum o bserved at the 3rd week, and then decreased to basal values (GHRH) or less (hexarelin) at the 6th week. These data would indicate that hexarelin initi ally primed the pituitary to acute administration of further hexarelin or o f GHRH, followed by downregulation of the GH response to hexarelin and pres ervation of the response to GHRH, We then studied the rebound increase in G H secretion after withdrawal of an infusion of somatostatin (4 mu g/kg per h for 1.5 h), a likely stimulus of endogenous GHRH function. The pattern ob tained was similar to, though not superimposable upon, that ensuing after a cute hexarelin or GHRH administration. Parallel evaluation of the acute ore xigenic effect of hexarelin evinced a different timecourse of the behaviour al response, namely an acute feeding response to hexarelin that was abolish ed at the 3rd week and returned to normal at the 6th week. The differing ti ming of the neuroendocrine or behavioural response to hexarelin would sugge st the existence of different subtypes of central nervous system GH-releasi ng peptide receptors.