Gronowski A M, Rotwein P
Department of Biochemistry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Endocrinology. 1995 Nov;136(11):4741-8. doi: 10.1210/endo.136.11.7588201.
GH exerts long-lasting effects on somatic growth via changes in gene expression and protein biosynthesis that represent the culmination of signal transduction pathways initiated at the cell surface. Recent studies have demonstrated that ligand-induced activation of the GH receptor leads to the phosphorylation of multiple intracellular proteins, including latent cytoplasmic transcription factors, Stats 1 and 3. GH treatment also has been found to induce the expression of several genes in both in vitro and in vivo systems, and we have shown that GH rapidly activates insulin-like growth factor I (IGF-I) gene transcription in hypophysectomized rats. In this study, using the GH-deficient, hypophysectomized rat as a model, we have examined the earliest changes in gene expression that follow a single systemic injection of GH. We find that GH induces nascent nuclear IGF-I transcripts within 15 min of hormone treatment, a time course that parallels the GH-regulated appearance of nuclear c-fos messenger RNA (mRNA). By contrast, nuclear transcripts for c-jun did not increase in abundance until after 30 min after hormone injection, and the peak rise in c-jun mRNA was severalfold less than for c-fos or IGF-I. GH treatment also led to the acute inhibition of IGF binding protein-1 (IGFBP-1) and albumin gene expression. Nuclear IGFBP-1 mRNA levels declined to 60% of baseline at 30 min and to 30% at 60 min, in agreement with previous studies showing a reduction in IGFBP-1 transcription after GH. Nascent nuclear albumin transcripts also decreased in abundance after GH treatment to levels that were less than 20% of basal values at 30 and 60 min. Our results show that GH can acutely activate and inhibit gene expression in the liver. It is likely that these diverse effects of GH are mediated by multiple signal transduction pathways.
生长激素（GH）通过基因表达和蛋白质生物合成的变化对体细胞生长产生持久影响，这些变化代表了在细胞表面启动的信号转导途径的最终结果。最近的研究表明，配体诱导的生长激素受体激活导致多种细胞内蛋白质的磷酸化，包括潜在的细胞质转录因子Stat1和Stat3。在体外和体内系统中，生长激素治疗也被发现可诱导多种基因的表达，并且我们已经表明，生长激素能迅速激活垂体切除大鼠体内胰岛素样生长因子I（IGF-I）基因的转录。在本研究中，我们以生长激素缺乏的垂体切除大鼠为模型，研究了单次全身注射生长激素后基因表达的最早变化。我们发现，生长激素在激素治疗后15分钟内即可诱导新生核IGF-I转录本的产生，这一时间段与生长激素调节的核c-fos信使核糖核酸（mRNA）的出现时间进程一致。相比之下，c-jun的核转录本在激素注射后30分钟后才开始增加，且c-jun mRNA的峰值升高幅度比c-fos或IGF-I低几倍。生长激素治疗还导致胰岛素样生长因子结合蛋白-1（IGFBP-1）和白蛋白基因表达的急性抑制。核IGFBP-1 mRNA水平在30分钟时降至基线的60%，在60分钟时降至30%，这与之前关于生长激素后IGFBP-1转录减少的研究结果一致。生长激素治疗后，新生核白蛋白转录本的丰度也降低，在30分钟和60分钟时降至基础值的20%以下。我们的结果表明，生长激素可在肝脏中急性激活和抑制基因表达。生长激素的这些不同作用可能是由多种信号转导途径介导的。
