Growth hormone-releasing hexapeptide is a potent stimulator of growth hormone gene expression and release in the growth hormone-releasing hormone-deprived infant rat.
The growth hormone-releasing hexapeptide (GHRP-6) specifically stimulates growth hormone (GH) secretion in several animal species and humans. The mechanism of action of GHRP-6 is largely unknown, although experimental evidence indicates that it may modulate growth hormone-releasing hormone (GHRH) and somatostatin actions at the pituitary or hypothalamic level. To gain more insight into the mechanism(s) of action of GHRP-6, we studied the infant rat, an animal model highly responsive to GH-releasing stimuli. In 14-d-old rats GHRP-6 (32-600 micrograms/kg, s.c.) induced a marked and dose-dependent rise in plasma GH concentrations, maximal stimulation occurring with the dose of 300 micrograms/kg. Neither GHRH nor somatostatin antiserum prevented or modified the GH release elicited by GHRP-6. In pups passively immunized with GHRH antibodies, a 5-d treatment with GHRP-6 (80 micrograms/kg, s.c., twice daily) completely counteracted the inhibitory effect of GHRH deprivation on GH mRNA expression. In vitro GHRP-6 (10(-7) and 10(-6) M) induced a small and transient stimulation of GH release from cultured pituitary cells. These results indicate the following: 1) GHRP-6 is a potent stimulator of GH release in rat pups; 2) it stimulates GH gene expression in the GHRH-deprived pup; 3) during the neonatal period its action is not mediated by GHRH or somatostatin; and 4) its actions are not directed at the somatotrophs.
Department of Pharmacology, School of Medicine, University of Milan, Italy.
V
V
Locatelli
R
R
Grilli
A
A
Torsello
S G
SG
Cella
W B
WB
Wehrenberg
E E
EE
Müller
D000818:Animals; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D013006:Growth Hormone / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000494:pharmacology*; D007116:Immunization, Passive; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009842:Oligopeptides; D012333:RNA, Messenger; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone