Effect of chronic administration of a new potent agonist of GH-RH(1-29)NH2 on linear growth and GH responsiveness in rats.
The effects of a repeated or continuous administration of a potent agonistic analog of growth hormone-releasing hormone (GH-RH), [Dat1, Thr8, Orn12,21, Abu15, Nle27, Asp28, Agm29] hGH-RH(1-29)(JI-36), on the linear growth and the GH responses to bolus injections of GH-RH(1-29)NH2 were investigated in male rats about 7 weeks old. Body weight and tail length were monitored. Basal serum GH and IGF-I concentrations and GH responses to GH-RH(1-29)NH2 were measured by RIA. Chronic administration of GH-RH agonist JI-36 by continuous release from osmotic minipumps at the rate of 0.2 microgram/h or twice daily injections of 0.5 and 5 micrograms/rat for 4 weeks significantly speeded up the growth of rats as measured by the tail length. The acceleration of growth was similar in the 3 groups and was associated with stimulation of IGF-I secretion. The GH response to bolus injection of GH-RH(1-29)NH2 was preserved in all groups and no attentuation of the response occurred in rats treated for 4 weeks with agonist JI-36 as compared with the control group. Our results indicate that chronic administration of GH-RH agonist JI-36 significantly increases the growth rate without affecting somatotroph responsiveness in rats. It is therefore likely that this class of GH-RH agonists may be useful clinically.
Pinski
J
J
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA, USA.
Izdebski
J
J
Jungwirth
A
A
Groot
K
K
Schally
A V
AV
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D013006:Growth Hormone / Q000097:blood / Q000494:pharmacology*; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015918:Infusion Pumps, Implantable; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail / Q000254:growth & development
D010446:Peptide Fragments; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone