Effect of long-term administration of an analog of growth hormone-releasing factor on the GH response in rats.
The effect of the repeated or continuous administration of an analog of GH releasing factor (GH-RF), D-Tyr-1, D-Ala-2, Nle-27, GH-RF(1-29)-NH2 (DBO-29), on the subsequent response to this peptide was investigated in pentobarbital-anesthetized male rats. A sc administration of this analog induced a greater and more prolonged GH release than doses 10 times larger of GH-RF(1-29). The GH increase after sc injection of 10 micrograms/kg bw of the analog was greater than that induced by iv administration of 2 micrograms/kg bw of GH-RF(1-44). Pretreatment with 10 micrograms/kg bw of the analog did not affect the pituitary response to a strong stimulus (20 micrograms/kg bw) of GH-RF(1-44), 24 h later. Pretreatment with the analog in doses of 10 micrograms/kg bw, sc twice a day, 5 days per week for 4 weeks, significantly diminished the GH release in response to a sc injection of the analog (10 micrograms/kg bw), as compared to vehicle-pretreated controls (P less than 0.01). On the other hand, a continuous sc administration of 0.4 micrograms/h of the analog to intact rats for 7 days did not result in a decrease in GH response to a sc injection of the analog (10 micrograms/kg bw). Since the rats injected repeatedly with the analog for 4 weeks still showed a marked, although somewhat reduced response, analogs of this type may be useful clinically.
D000818:Animals; D013006:Growth Hormone / Q000097:blood*; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017337:Sermorelin / Q000031:analogs & derivatives; D013997:Time Factors
D010446:Peptide Fragments; C040786:somatotropin releasing hormone (1-44)amide; C052685:DBO 29; D017337:Sermorelin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone