Role of the Growth Hormone Binding Protein as a Transcriptional Activator

生长激素是治疗侏儒症的重要激素。最近，生长激素的许多新的治疗应用被发现，特别是与其作为合成代谢试剂的作用有关。这些问题包括术后恢复、骨折愈合增强、克罗恩氏病、扩张型心肌病、不孕症，当然还有衰老。这项提议研究了生长激素的一种新的工作方式，即通过将其受体的胞外部分(GHBP)发送到细胞核，在那里它可以直接激活基因读出。这将具有增强生长激素调节基因读出的正常作用的效果。我们有令人兴奋的初步数据，这让我们认为这可能是激素激活基因的一种新机制。细胞核中的GHBP水平是受调控的，如果GHBP的出口出现缺陷，这将导致细胞核GHBP的积聚，并刺激细胞增殖。这在癌细胞增殖中可能很重要，因为我们在癌症中发现了核GHBP。

Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its role as an anabolic agent. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and of course, ageing. This proposal examines a novel way that GH could work, that is by sending the extracellular part of its receptor (GHBP) to the nucleus, where it can directly activate gene readout. This would have the effect of augmenting the normal action of GH to regulate gene readout. We have exciting preliminary data which makes us think this may be a new mechanism for hormone activation of genes. The level of GHBP in the nucleus is regulated, and if a defect in export of the GHBP occurred, this would lead to accumulation of nuclear GHBP and stimulate cell proliferation. This may be important in cancer cell proliferation, since we find nuclear GHBP in cancers.