Genetic Programs Induced by Growth Hormone

生长激素负责正常的出生后生长，是饥饿时重要的代谢调节剂，有许多有用的治疗应用，包括各种形式的心功能不全、克罗恩病以及被认为是延缓衰老。尽管我们确实对生长激素受体内的个体区域如何发出信号有相当多的了解，但生长激素带来这些变化的途径尚不清楚。我们不知道的是在这些过程中哪些基因受到生长激素的调节，以及这将如何改变细胞的状态。我们在此建议使用基因阵列的新技术来揭示生长激素调节改变重要细胞过程的程序或基因群。当与表达生长激素受体突变的细胞一起使用时，我们将能够知道哪些功能家族基因受到调节，以及它们是如何被调节的。这些信息将使我们了解生长激素如何调节细胞生长和代谢，从而了解当生长激素或其中介物IGF-1异常时出现的问题。我们也可以利用这些信息来验证通过激活受体来模拟生长激素的小分子，以确定它们的作用方式与生长激素相同。

Growth hormone is responsible for normal postnatal growth, is an important metabolic regulator in starvation, and has many useful therapeutic applications, including forms of cardiac insufficiency, Crohns disease and, it is thought, amelioration of ageing. The means whereby GH brings about these changes are not known, although we do know a considerable amount about how the individual domains within the GH receptor signal. What we do not know is which genes are regulated by GH in these processes, and how this will change the state of the cell. We propose here to use the new technique of gene arrays to uncover the programs, or groups of genes, which GH regulates to change important cellular processes. When used in conjunction with cells expressing GH receptor mutants which are unable to signal to defined pathways, we will be able to know which functional families genes are regulated, and how they are regulated. This information will enable us to know how GH regulates cell growth and metabolism, and therfore to understand what goes wrong when GH or its mediator, IGF-1 , are abnormal. We can also use this information to validate small molecules designed to mimic GH through activating its receptor, to be certain that they are acting in the same way as GH.