Cone Roger D
Center for the Study of Weight Regulation and Associated Disorders, and Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239-3098, USA.
Endocr Rev. 2006 Dec;27(7):736-49. doi: 10.1210/er.2006-0034. Epub 2006 Oct 31.
The melanocortin system refers to a set of hormonal, neuropeptidergic, and paracrine signaling pathways that are defined by components that include the five G protein-coupled melanocortin receptors; peptide agonists derived from the proopiomelanocortin preprohormone precursor; and the endogenous antagonists, agouti and agouti-related protein. This signaling system regulates a remarkably diverse array of physiological functions including pigmentation, adrenocortical steroidogenesis, energy homeostasis, natriuresis, erectile responses, energy homeostasis, and exocrine gland secretion. There are many complex and unique aspects of melanocortin signaling, such as the existence of endogenous antagonists, the agouti proteins, that act at three of the five melanocortin receptors. However, there is an aspect of melanocortin signaling that has facilitated highly reductionist approaches aimed at understanding the physiological functions of each receptor and peptide: in contrast to many peptides, the melanocortin agonists and antagonists are expressed in a limited number of very discrete locations. Similarly, the melanocortin receptors are also expressed in a limited number of discrete locations where they tend to be involved in rather circumscribed physiological functions. This review examines my laboratory's participation in the cloning of the melanocortin receptors and characterization of their physiological roles.
黑皮质素系统是指一组激素、神经肽和旁分泌信号通路，其由包括五种G蛋白偶联黑皮质素受体的成分所定义；源自阿黑皮素原前体激素前体的肽激动剂；以及内源性拮抗剂刺鼠信号蛋白和刺鼠相关蛋白。该信号系统调节一系列极为多样的生理功能，包括色素沉着、肾上腺皮质类固醇生成、能量稳态、利钠作用、勃起反应、能量稳态以及外分泌腺分泌。黑皮质素信号传导存在许多复杂且独特的方面，例如内源性拮抗剂刺鼠信号蛋白的存在，其作用于五种黑皮质素受体中的三种。然而，黑皮质素信号传导有一个方面有助于采用高度简化论的方法来理解每种受体和肽的生理功能：与许多肽不同，黑皮质素激动剂和拮抗剂在数量有限的非常离散的位置表达。同样，黑皮质素受体也在数量有限的离散位置表达，在这些位置它们往往参与相当局限的生理功能。本综述考察了我的实验室在黑皮质素受体克隆及其生理作用表征方面所做的工作。
