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

我感兴趣的是一种罕见的疾病，称为家族性糖皮质激素缺乏症（FGD）。患有这种疾病的患者没有科普压力的机制。如果他们的身体变得紧张，例如疾病，他们的血糖水平下降，他们变得容易感染，如果不治疗，他们可能会死亡。促肾上腺皮质激素是在应激反应中产生的激素，促肾上腺皮质激素受体是识别促肾上腺皮质激素并引起帮助身体科普应激的变化的蛋白质。FGD可由缺陷的ACTH受体（ACTHR）引起，占所有病例的四分之一。在其他四分之三的ACTHR是正常的。然而，我们最近发现了另一种名为MRAP的基因也会导致这种疾病。这个基因制造一种蛋白质，这种蛋白质是ACTHR正常运作所必需的。这种机制究竟是如何工作的还不完全清楚，我们相信其他基因也可能是必要的。目前，我们正在寻找这些基因，看看它们是否与ACTHR和MRAP相互作用，并通过研究FGD患者的遗传组成。当我们找到这些其他基因并发现它们的作用时，我们将更好地了解这种激素受体是如何工作的。我们希望这一知识也可以揭示其他疾病，如儿童肥胖症，这是由类似的受体系统缺陷引起的。

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.