Murphy L J, Bell G I, Duckworth M L, Friesen H G
Endocrinology. 1987 Aug;121(2):684-91. doi: 10.1210/endo-121-2-684.
A complementary DNA (cDNA) encoding rat insulin-like growth factor 1 (IGF-I) has been isolated from a kidney cDNA library. By analogy with the sequence of human and mouse preproIGF-IA this cDNA encodes rat preproIGF-I from amino acid minus 3 to amino acid 105. The predicted protein sequence shows 96% and 99% homology with the human and mouse preproIGF-I, respectively. Under stringent conditions the rat IGF-I cDNA hybridizes with at least three mRNA, messenger RNA species which have apparent sizes of 7, 1.8, and 0.7-1.1 kilobases. All three IGF-I transcripts are detectable in each of the normal rat tissues examined and the relative order of abundance in tissues from intact adult male rats is liver greater than lung greater than kidney greater than thymus greater than spleen greater than heart greater than skeletal muscle (quadriceps femoris) greater than testes greater than brain. The GH dependence of the IGF-I mRNAs was demonstrated by the administration of a single ip injection of human GH (hGH) to hypophysectomized (hypox) rats which resulted in an increase in all three transcripts in each of the tissues examined. The increase in IGF-1 mRNAs was most marked in skeletal and cardiac muscle (9.7- and 9.5-fold compared to hypox controls, respectively) and least marked in the brain. In the liver only a 4-fold increase in IGF-I expression was observed, possibly because of the relatively high level of IGF-I expression in the tissue in the hypox control rats. Each of the IGF-I messenger RNAs appeared to increase in parallel and the time course of IGF-I induction was similar in each tissue with maximal levels of IGF-I transcripts present 6 to 12 h after GH administration. A dose-dependent increase in IGF-I mRNAs was observed in most tissues of hypox rats treated for 10 days with hGH. Significant correlations between growth, as determined by body weight gain and IGF-I expression were observed in liver (r = 0.97), kidney (r = 0.90), quadriceps femoris (r = 0.95), diaphragm (r = 0.92), and thymus (r = 1.0). The IGF-I mRNA levels in tissues from rats that had been treated with the highest dose of hGH (90 microgram/rat X day) were similar to those observed in normal intact rats. This study confirms the highly conserved nature of the IGF-I precursor and provides clear evidence for the GH dependence of IGF-I gene expression in multiple tissues of the rat.
已从大鼠肾脏cDNA文库中分离出编码大鼠胰岛素样生长因子1（IGF-I）的互补DNA（cDNA）。根据人和小鼠前胰岛素原IGF-IA的序列类推，该cDNA编码从氨基酸-3至氨基酸105的大鼠前胰岛素原IGF-I。预测的蛋白质序列与人及小鼠前胰岛素原IGF-I的同源性分别为96%和99%。在严格条件下，大鼠IGF-I cDNA与至少三种mRNA杂交，这三种信使RNA的表观大小分别为7、1.8和0.7 - 1.1千碱基。在所检测的每一种正常大鼠组织中均能检测到所有三种IGF-I转录本，在成年雄性完整大鼠组织中的相对丰度顺序为：肝脏＞肺＞肾脏＞胸腺＞脾脏＞心脏＞骨骼肌（股四头肌）＞睾丸＞脑。通过对垂体切除（hypox）大鼠单次腹腔注射人生长激素（hGH）来证明IGF-I mRNA对生长激素的依赖性，这导致在所检测的每一种组织中所有三种转录本均增加。IGF-1 mRNA的增加在骨骼肌和心肌中最为显著（分别比hypox对照高9.7倍和9.5倍），在脑中最不显著。在肝脏中仅观察到IGF-I表达增加4倍，这可能是因为hypox对照大鼠组织中IGF-I表达水平相对较高。每一种IGF-I信使RNA似乎都平行增加，并且IGF-I诱导的时间进程在各组织中相似，在给予生长激素后6至12小时出现IGF-I转录本的最高水平。在用hGH处理10天的hypox大鼠的大多数组织中观察到IGF-I mRNA呈剂量依赖性增加。在肝脏（r = 0.97）、肾脏（r = 0.90）、股四头肌（r = 0.95）、膈肌（r = 0.92）和胸腺（r = 1.0）中，观察到生长（通过体重增加确定）与IGF-I表达之间存在显著相关性。用最高剂量hGH（90微克/大鼠×天）处理的大鼠组织中的IGF-I mRNA水平与正常完整大鼠中观察到的水平相似。本研究证实了IGF-I前体的高度保守性质，并为大鼠多种组织中IGF-I基因表达对生长激素的依赖性提供了明确证据。
