Anderson Erica J P, Çakir Isin, Carrington Sheridan J, Cone Roger D, Ghamari-Langroudi Masoud, Gillyard Taneisha, Gimenez Luis E, Litt Michael J
Department of Molecular Physiology and BiophysicsVanderbilt University School of Medicine, Nashville, Tennessee, USA.
Department of Molecular Physiology and BiophysicsVanderbilt University School of Medicine, Nashville, Tennessee, USA
J Mol Endocrinol. 2016 May;56(4):T157-74. doi: 10.1530/JME-16-0014. Epub 2016 Mar 3.
The melanocortin peptides derived from pro-opiomelanocortin (POMC) were originally understood in terms of the biological actions of α-melanocyte-stimulating hormone (α-MSH) on pigmentation and adrenocorticotrophic hormone on adrenocortical glucocorticoid production. However, the discovery of POMC mRNA and melanocortin peptides in the CNS generated activities directed at understanding the direct biological actions of melanocortins in the brain. Ultimately, discovery of unique melanocortin receptors expressed in the CNS, the melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors, led to the development of pharmacological tools and genetic models leading to the demonstration that the central melanocortin system plays a critical role in the regulation of energy homeostasis. Indeed, mutations in MC4R are now known to be the most common cause of early onset syndromic obesity, accounting for 2-5% of all cases. This review discusses the history of these discoveries, as well as the latest work attempting to understand the molecular and cellular basis of regulation of feeding and energy homeostasis by the predominant melanocortin peptide in the CNS, α-MSH.
源自阿黑皮素原（POMC）的促黑素细胞激素肽最初是根据α-促黑素细胞激素（α-MSH）对色素沉着的生物学作用以及促肾上腺皮质激素对肾上腺皮质糖皮质激素产生的作用来理解的。然而，在中枢神经系统中发现POMC信使核糖核酸（mRNA）和促黑素细胞激素肽引发了旨在了解促黑素细胞激素在大脑中的直接生物学作用的研究活动。最终，在中枢神经系统中发现了独特的促黑素细胞激素受体，即促黑素细胞激素-3（MC3R）和促黑素细胞激素-4（MC4R）受体，这导致了药理学工具和遗传模型的开发，从而证明中枢促黑素细胞激素系统在能量稳态调节中起关键作用。事实上，现在已知MC4R突变是早发性综合征性肥胖最常见的原因，占所有病例的2%至5%。本综述讨论了这些发现的历史，以及试图了解中枢神经系统中主要促黑素细胞激素肽α-MSH调节进食和能量稳态的分子和细胞基础的最新研究工作。
