Gosteli-Peter M A, Winterhalter K H, Schmid C, Froesch E R, Zapf J
Department of Internal Medicine, University Hospital Zurich, Switzerland.
Endocrinology. 1994 Dec;135(6):2558-67. doi: 10.1210/endo.135.6.7527334.
The expression and regulation of insulin-like growth factor-I (IGF-I) and IGF-binding protein-2 (IGFBP-2), -3, -4, and -5 messages were studied in liver, kidney, spleen, thymus, heart, brain, skeletal muscle, testes, and epididymal (white) adipose tissue (WAT) from hypophysectomized rats infused with saline, recombinant human (rh) IGF-I, or rhGH and compared with tissue messenger RNA (mRNA) levels in age-matched normal rats. The IGF-I message was present in all of these tissues. It was most abundant in liver and WAT, but was barely detectable in kidney, brain, and thymus. GH dependence was most pronounced in liver, skeletal muscle, and WAT and less so in heart, testes, kidney, spleen, and thymus. The IGF-I message in brain was not influenced by hypophysectomy. IGF-I infusion induced a small increase in its own mRNA in skeletal muscle and WAT, whereas it decreased its own message in liver. IGFBPs were expressed in a tissue-specific manner; IGFBP-2 mRNA was most abundant in testes and hypophysectomized liver, IGFBP-3 mRNA was most abundant in spleen, kidney, WAT, and liver, IGFBP-4 mRNA was most abundant in liver, and IGFBP-5 mRNA was most abundant in kidney, WAT, and skeletal muscle. After hypophysectomy, significant decreases in IGFBP expression were observed in liver (except IGFBP-2), skeletal muscle, brain, WAT (except IGFBP-4), and testes (except IGFBP-2), in contrast to heart, kidney, spleen, and thymus. GH infusion did not affect IGFBP-2 mRNA levels in liver (in contrast to IGF-I infusion) or brain. Like GH, IGF-I normalized IGFBP-3 mRNA levels in liver, but, in contrast to GH, had no effect on IGFBP-5 mRNA in WAT. It was considerably less effective than GH in raising IGFBP-5 mRNA levels in skeletal muscle. Thus, GH infusion can exert different effects on IGF-I and IGFBP expression than infused rhIGF-I. Differences may be due to direct actions of GH at the tissue level, including auto/paracrine effects of locally produced IGF-I.
研究了垂体切除大鼠经生理盐水、重组人生长激素（rhGH）或重组人胰岛素样生长因子-I（IGF-I）灌注后，肝脏、肾脏、脾脏、胸腺、心脏、大脑、骨骼肌、睾丸和附睾（白色）脂肪组织（WAT）中胰岛素样生长因子-I（IGF-I）及IGF结合蛋白-2（IGFBP-2）、-3、-4和-5信使核糖核酸（mRNA）的表达及调控情况，并与年龄匹配的正常大鼠的组织信使核糖核酸（mRNA）水平进行了比较。IGF-I信使核糖核酸存在于所有这些组织中。它在肝脏和WAT中最为丰富，但在肾脏、大脑和胸腺中几乎检测不到。生长激素依赖性在肝脏、骨骼肌和WAT中最为明显，在心脏、睾丸、肾脏、脾脏和胸腺中则较弱。大脑中的IGF-I信使核糖核酸不受垂体切除的影响。IGF-I灌注使骨骼肌和WAT中其自身的mRNA略有增加，而在肝脏中则使其自身的信使核糖核酸减少。IGF结合蛋白以组织特异性方式表达；IGFBP-2 mRNA在睾丸和垂体切除后的肝脏中最为丰富，IGFBP-3 mRNA在脾脏、肾脏、WAT和肝脏中最为丰富，IGFBP-4 mRNA在肝脏中最为丰富，IGFBP-5 mRNA在肾脏、WAT和骨骼肌中最为丰富。垂体切除后，肝脏（IGFBP-2除外）、骨骼肌、大脑、WAT（IGFBP-4除外）和睾丸（IGFBP-2除外）中IGFBP表达显著降低，而心脏、肾脏、脾脏和胸腺则相反。生长激素灌注不影响肝脏（与IGF-I灌注相反）或大脑中的IGFBP-2 mRNA水平。与生长激素一样，IGF-I使肝脏中的IGFBP-3 mRNA水平恢复正常，但与生长激素相反，对WAT中的IGFBP-5 mRNA没有影响。在提高骨骼肌中IGFBP-5 mRNA水平方面，它比生长激素的效果要差得多。因此，生长激素灌注对IGF-I和IGFBP表达的影响可能与灌注rhIGF-I不同。差异可能是由于生长激素在组织水平的直接作用，包括局部产生的IGF-I的自分泌/旁分泌作用。
