Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239-3098, USA.
Pediatr Nephrol. 2010 Apr;25(4):651-8. doi: 10.1007/s00467-009-1258-y. Epub 2009 Jul 22.
Since the somatomedin hypothesis of growth hormone (GH) action was first formulated more than 50 years ago, the key roles of both GH and insulin-like growth factor-I (IGF-I) in human growth have been extended to include important effects on tissue maintenance and repair. More recent observations have revealed that this pathway has a negative side, as it has been implicated as a potential contributor to the development of several human cancers and has been linked to diminished lifespan in experimental animals. This brief review focuses on fundamental aspects of gene regulation by GH, as long-term hormonal effects all require changes in gene expression. Topics to be discussed include GH-stimulated signal transduction pathways, mechanisms of gene activation and gene repression by GH, and an analysis of control of IGF-I gene transcription by the GH-stimulated transcription factor, signal transducer and activator of transcription (Stat)5b.
自 50 多年前生长激素(GH)作用的 somatomedin 假说首次提出以来,GH 和胰岛素样生长因子-I(IGF-I)在人类生长中的关键作用已扩展到包括对组织维持和修复的重要影响。最近的观察结果表明,该途径有一个负面的方面,因为它被认为是几种人类癌症发展的潜在因素,并与实验动物寿命缩短有关。这篇简短的综述侧重于 GH 对基因调控的基本方面,因为长期的激素作用都需要基因表达的改变。要讨论的主题包括 GH 刺激的信号转导途径、GH 激活和抑制基因的机制,以及 GH 刺激的转录因子信号转导和转录激活物(Stat)5b 对 IGF-I 基因转录的控制分析。