Clark R G, Mortensen D L, Carlsson L M
Endocrine Research Department, Genentech, Inc., 460 Pt. San Bruno Blvd., 94080-4990, South San Francisco, California, USA.
Endocrine. 1995 Apr;3(4):297-304. doi: 10.1007/BF03021409.
The anabolic activity of recombinant human growth hormone (rhGH) and insulin-like growth factor 1 (rhlGF-1) given either alone or together were studied in two models of GH deficiency, hypophysectomized and GH-deficient dwarf rats. A range of rhGH doses (0.08 to 50 mg/kg/day, seven daily sc injections) were given either alone or together with one dose of rhIGF-l (2.4 mg/kg/day, sc infusion). When given alone, or co-administered with rhlGF-1, rhGH produced dose dependent increases in weight gain, bone growth and organ weights. Weight gain in response to rhGH given with rhlGF-1 was comparable to that obtained by a 25-fold higher dose of rhGH given alone. In both animal models absolute weights of the kidneys, liver, spleen and thymus were increased by rhlGF-1 while kidney and liver weight were increased by rhGH. In the hypophysectomized rat, spleen and thymus weights were increased by rhGH but the relative potency of the combination was a 1000-fold that of rhGH alone. The effects of rhlGF-1 and rhGH were additive indicating that the effects of GH or IGF-1 can be greatly increased by their co-administration.
在两种生长激素缺乏模型(垂体切除的大鼠和生长激素缺乏的侏儒大鼠)中,研究了单独给予或联合给予重组人生长激素(rhGH)和胰岛素样生长因子1(rhIGF-1)的合成代谢活性。给予一系列rhGH剂量(0.08至50mg/kg/天,每日皮下注射7次),单独给予或与一剂rhIGF-1(2.4mg/kg/天,皮下输注)联合给予。单独给予rhGH或与rhIGF-1共同给药时,rhGH均可使体重增加、骨骼生长和器官重量呈剂量依赖性增加。与rhIGF-1联合给予rhGH时的体重增加与单独给予高25倍剂量的rhGH时相当。在两种动物模型中,rhIGF-1可增加肾脏、肝脏、脾脏和胸腺的绝对重量,而rhGH可增加肾脏和肝脏的重量。在垂体切除的大鼠中,rhGH可增加脾脏和胸腺的重量,但联合用药的相对效力是单独使用rhGH的1000倍。rhIGF-1和rhGH的作用是相加的,这表明联合给药可大大增强生长激素或胰岛素样生长因子-1的作用。