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大鼠生长激素多克隆抗血清对循环胰岛素样生长因子(IGF)-I、IGF结合蛋白浓度以及肌肉和骨骼生长的影响。

Effects of a polyclonal antiserum to rat growth hormone on circulating insulin-like growth factor (IGF)-I and IGF-binding protein concentrations and the growth of muscle and bone.

作者信息

Palmer R M, Loveridge N, Thomson B M, Mackie S C, Tonner E, Flint D J

机构信息

Rowett Research Institute, Bucksburn, Aberdeen, UK.

出版信息

J Endocrinol. 1994 Jul;142(1):85-91. doi: 10.1677/joe.0.1420085.

DOI:10.1677/joe.0.1420085
PMID:7525823
Abstract

A polyclonal antiserum to rat GH (anti-rGH) injected into rats for 3 or 8 weeks markedly reduced the weight, total protein and RNA content of muscles of the hind limb. These effects were prevented when bovine GH (bGH) was administered simultaneously. In a second experiment, the effects of 8 weeks of treatment with anti-rGH on the growth of the whole body, muscle and bone were investigated. Body weights of rats were decreased by 58% by treatment with anti-rGH; muscle weights were reduced by slightly more than the decrease in body weight (by 64%, 65% and 61% respectively for plantaris, soleus and gastrocnemius). The weight of the tibia was decreased by 54%, its length was decreased by 23%, cortical width and overall width were reduced by 26% and 18% respectively, suggesting a possible role for GH in osteoclastic activity. Serum total insulin-like growth factor-I (IGF-I) concentrations were decreased by 80-90% in both experiments by anti-rGH; these changes were prevented in the first experiment by concurrent treatment with anti-rGH and bGH. The serum IGF-binding protein-3 (IGFBP-3) concentration was also decreased by anti-rGH in experiment 1 (by 86%); the response of the 28-32 kDa IGFBPs was smaller (-35%), and was restored to control values by simultaneous injection of bGH. Western immunoblotting using an antiserum to IGFBP-2 showed that there was a marked decrease from neonatal to adult stages which was independent of anti-rGH treatment. This clearly demonstrated a dissociation of the reciprocal relationship supposed to exist between IGFBPs-2 and -3. The 24 kDa IGFBP-4 was unaffected by anti-rGH but replacement therapy with bGH doubled its concentration. Although the effects on body and muscle weight were prevented when rats were given anti-rGH and bGH simultaneously, the possibility of mediation by other hormones cannot be precluded.

摘要

给大鼠注射抗大鼠生长激素(anti-rGH)3周或8周,显著降低了后肢肌肉的重量、总蛋白和RNA含量。同时给予牛生长激素(bGH)可防止这些作用。在第二个实验中,研究了anti-rGH治疗8周对全身、肌肉和骨骼生长的影响。用anti-rGH治疗使大鼠体重降低了58%;肌肉重量的降低略高于体重的降低(比目鱼肌、比目鱼肌和腓肠肌分别降低了64%、65%和61%)。胫骨重量降低了54%,长度降低了23%,皮质宽度和整体宽度分别降低了26%和18%,提示生长激素在破骨细胞活性中可能起作用。在两个实验中,anti-rGH均使血清总胰岛素样生长因子-I(IGF-I)浓度降低了80-90%;在第一个实验中,同时给予anti-rGH和bGH可防止这些变化。在实验1中,anti-rGH也降低了血清IGF结合蛋白-3(IGFBP-3)浓度(降低了86%);28-32 kDa IGFBPs的反应较小(降低了35%),同时注射bGH可使其恢复到对照值。使用抗IGFBP-2抗血清进行的Western免疫印迹显示,从新生期到成年期有明显下降,且与anti-rGH治疗无关。这清楚地证明了IGFBP-2和-3之间本应存在的相互关系的解离。24 kDa IGFBP-4不受anti-rGH影响,但用bGH替代疗法可使其浓度增加一倍。尽管同时给予anti-rGH和bGH可防止对体重和肌肉重量的影响,但不能排除其他激素介导的可能性。

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