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
Ae. Rigamonti et al., 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, EUR J ENDOC, 141(3), 1999, pp. 313-320
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.