TY - JOUR
T1 - Effect of long-term administration of an analog of growth hormone-releasing factor on the GH response in rats
AU - Karashima, Tsuyoshi
AU - Olsen, Donald
AU - Schally, Andrew V.
N1 - Funding Information:
We thank Martha Sampson for experimental assistance and the National Hormone and Pituitary Program (NIIPP) for the gifts of materials used in radiolmmunoassays. The work described in this paper was supported by the National Institutes of Health Grants DK07467 and CA 40003, (to A.V.S.) and by the Medical Research Service of the Veterans Administration.
PY - 1987/6/22
Y1 - 1987/6/22
N2 - 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 μg/kg bw of the analog was greater than that induced by iv administration of 2 μg/kg bw of GH-RF(1-44). Pretreatment with 10 μg/kg bw of the analog did not affect the pituitary response to a strong stimulus (20 μg/kg bw) of GH-RF(1-44), 24 h later. Pretreatment with the analog in doses of 10 μg/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 μg/kg bw), as compared to vehicle-pretreated controls (P <0.01). On the other hand, a continuous sc administration of 0.4 μg/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 μg/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.
AB - 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 μg/kg bw of the analog was greater than that induced by iv administration of 2 μg/kg bw of GH-RF(1-44). Pretreatment with 10 μg/kg bw of the analog did not affect the pituitary response to a strong stimulus (20 μg/kg bw) of GH-RF(1-44), 24 h later. Pretreatment with the analog in doses of 10 μg/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 μg/kg bw), as compared to vehicle-pretreated controls (P <0.01). On the other hand, a continuous sc administration of 0.4 μg/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 μg/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.
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U2 - 10.1016/0024-3205(87)90759-4
DO - 10.1016/0024-3205(87)90759-4
M3 - Article
C2 - 2884550
AN - SCOPUS:0023223854
VL - 40
SP - 2437
EP - 2444
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 25
ER -