Division of Medicine, Norfolk and Norwich University Hospital, Colney Lane, Norwich, NR4 7UZ, UK.
Nutr Metab (Lond). 2007 Sep 1;4:18. doi: 10.1186/1743-7075-4-18.
The precursor protein, proopiomelanocortin (POMC), produces many biologically active peptides via a series of enzymatic steps in a tissue-specific manner, yielding the melanocyte-stimulating hormones (MSHs), corticotrophin (ACTH) and beta-endorphin. The MSHs and ACTH bind to the extracellular G-protein coupled melanocortin receptors (MCRs) of which there are five subtypes. The MC3R and MC4R show widespread expression in the central nervous system (CNS), whilst there is low level expression of MC1R and MC5R. In the CNS, cell bodies for POMC are mainly located in the arcuate nucleus of the hypothalamus and the nucleus tractus solitarius of the brainstem. Both of these areas have well defined functions relating to appetite and food intake. Mouse knockouts (ko) for pomc, mc4r and mc3r all show an obese phenotype, as do humans expressing mutations of POMC and MC4R. Recently, human subjects with specific mutations in beta-MSH have been found to be obese too, as have mice with engineered beta-endorphin deficiency. The CNS POMC system has other functions, including regulation of sexual behaviour, lactation, the reproductive cycle and possibly central cardiovascular control. However, this review will focus on feeding behaviour and link it in with the neuroanatomy of the POMC neurones in the hypothalamus and brainstem.
前体蛋白，促黑激素原（POMC），通过一系列组织特异性的酶促步骤产生许多生物活性肽，产生黑素细胞刺激激素（MSH）、促肾上腺皮质激素（ACTH）和β-内啡肽。MSH 和 ACTH 与细胞外 G 蛋白偶联的黑皮质素受体（MCR）结合，其中有五种亚型。MC3R 和 MC4R 在中枢神经系统（CNS）中广泛表达，而 MC1R 和 MC5R 的表达水平较低。在中枢神经系统中，POMC 的细胞体主要位于下丘脑的弓状核和脑干的孤束核。这两个区域都有明确的与食欲和食物摄入相关的功能。pomc、mc4r 和 mc3r 的小鼠敲除（ko）都表现出肥胖表型，表达 POMC 和 MC4R 突变的人类也是如此。最近，发现具有特定β-MSH 突变的人类也肥胖，具有工程化β-内啡肽缺乏的小鼠也是如此。CNS POMC 系统具有其他功能，包括调节性行为、哺乳、生殖周期和可能的中枢心血管控制。然而，本综述将重点关注进食行为，并将其与下丘脑和脑干中 POMC 神经元的神经解剖学联系起来。
