ACTH receptor pathway defects as the cause of Familial Glucocorticoid Deficiency type 3 (FGD3)

ACTH 受体通路缺陷是导致 3 型家族性糖皮质激素缺乏症 (FGD3) 的原因

• 批准号: G0801265/1
• 负责人: Louise Metherell
• 金额: $ 63.18万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0801265%2F1
• 关键词: ACTH; receptor; pathway; defects; cause

I am interested in a rare disease called Familial Glucocorticoid Deficiency (FGD). Patients with this disease do not have a mechanism to cope with stress. If their body becomes stressed, for example by illness, their blood sugar levels drop, they become liable to infections and they may die if untreated. ACTH is the hormone that is produced in response to stress and the ACTH receptor is the protein that recognises ACTH and causes the changes that help the body to cope with the stress. FGD can be caused by a defective ACTH receptor (ACTHR) in a quarter of all cases. In the other three quarters the ACTHR is normal. However we have recently discovered another gene called MRAP that also causes the disease. This gene makes a protein that is needed for the correct functioning of the ACTHR. Exactly how this mechanism works is not fully understood and we believe that other genes may also be necessary. Currently we are searching for these genes by seeing if they interact with the ACTHR and MRAP and by studying the genetic make-up of FGD patients. When we find these other genes and find out what they do we will have a better understanding of how this hormone receptor works. We hope that this knowledge may also shed light on other diseases, such as childhood obesity, that are caused by defects in similar receptor systems.

我对一种名为家族性糖皮质激素缺乏症 (FGD) 的罕见疾病感兴趣。患有这种疾病的患者没有应对压力的机制。如果他们的身体受到压力（例如因疾病），他们的血糖水平就会下降，他们就容易受到感染，如果不及时治疗，他们可能会死亡。 ACTH 是响应压力而产生的激素，ACTH 受体是识别 ACTH 并引起变化以帮助身体应对压力的蛋白质。四分之一的 FGD 可能是由 ACTH 受体 (ACTHR) 缺陷引起的。其他四分之三的 ACTHR 正常。然而，我们最近发现了另一种称为 MRAP 的基因也会导致这种疾病。该基因产生一种 ACTHR 正常运作所需的蛋白质。这种机制到底是如何运作的尚不完全清楚，我们相信其他基因可能也是必要的。目前，我们正在通过观察这些基因是否与 ACTHR 和 MRAP 相互作用以及研究 FGD 患者的基因组成来寻找这些基因。当我们找到这些其他基因并了解它们的作用时，我们将更好地了解这种激素受体的工作原理。我们希望这一知识也能揭示其他疾病，例如由类似受体系统缺陷引起的儿童肥胖症。