Functional analysis of naturally occurring mutations of the ACTH receptor and identification of trafficking defects

肾上腺会产生几种调节身体功能的荷尔蒙。其中一种叫做皮质醇的荷尔蒙是生存所必需的。皮质醇由另一种名为ACTH的荷尔蒙直接调节，这种荷尔蒙是由大脑中的脑下垂体产生的。ACTH直接作用于肾上腺表面的一种称为ACTH受体的蛋白质。ACTH受体基因的突变被认为是导致被称为家族性糖皮质激素缺乏症的遗传综合征的原因，现在已经在这种疾病中发现了大量这样的突变。该项目将调查这些突变对受体的影响，并指出它们是否确实是疾病的原因，如果是，它们以何种方式干扰受体功能。在公共卫生方面，对导致这种疾病的突变受体的研究将揭示该受体的机制，并可能揭示其他相关受体的机制，如参与食欲调节并与人类肥胖有关的MC4受体。

The adrenal gland produces several hormones that regulate body function. One of these hormones called cortisol is essential for survival. Cortisol is directly regulated by another hormone called ACTH produced by the pituitary gland in the brain. ACTH acts directly on a protein on the adrenal gland surface called the ACTH receptor. Mutations in the ACTH receptor gene are believed to cause the inherited syndrome known as Familial Glucocorticoid Deficiency, and a large number of such mutations have now been identified in this disease. This project will investigate the consequences of these mutations on the receptor and indicate whether they are indeed the cause of the disease and, if so, in what way they interfere with receptor function. In public health terms, the study of mutant receptors causing this disease will reveal aspects of the mechanism of this receptor and potentially of other related receptors such as the MC4 receptor which is involved in appetite regulation and is associated with human obesity.