Karashima T, Olsen D, Schally A V
Life Sci. 1987 Jun 22;40(25):2437-44. doi: 10.1016/0024-3205(87)90759-4.
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.
在戊巴比妥麻醉的雄性大鼠中，研究了生长激素释放因子（GH-RF）类似物D-Tyr-1、D-Ala-2、Nle-27、GH-RF(1-29)-NH2（DBO-29）重复或持续给药对随后对该肽反应的影响。皮下注射这种类似物比10倍剂量的GH-RF(1-29)诱导出更大且更持久的生长激素释放。皮下注射10微克/千克体重该类似物后生长激素的增加大于静脉注射2微克/千克体重GH-RF(1-44)所诱导的增加。24小时后，用10微克/千克体重该类似物预处理不影响垂体对20微克/千克体重GH-RF(1-44)强烈刺激的反应。与溶媒预处理的对照组相比，以10微克/千克体重的剂量皮下注射该类似物，每天两次，每周5天，共4周，显著降低了对皮下注射该类似物（10微克/千克体重）的生长激素释放（P<0.01）。另一方面，对完整大鼠连续7天皮下注射0.4微克/小时该类似物，并未导致对皮下注射该类似物（10微克/千克体重）的生长激素反应降低。由于反复注射该类似物4周的大鼠仍显示出明显的反应，尽管有所降低，这类类似物在临床上可能有用。
