Voisey J, Carroll L, van Daal A
Co-operative Research Centre for Diagnostics, Queensland University of Technology, Brisbane, 4000, Australia.
Curr Drug Targets. 2003 Oct;4(7):586-97. doi: 10.2174/1389450033490858.
The melanocortins are a group of small protein hormones derived by post-translational cleavage of the proopiomelanocortin (POMC) gene product. The known melanocortin hormones include alpha-melanocyte stimulating hormone (MSH), beta-MSH, gamma-MSH and adrenocorticotropic hormone (ACTH). Five melanocortin receptors (MCIR through to MC5R) have been identified and most of these show tissue-specific expression patterns, as well as different binding affinities for each of the melanocortin hormones. The central melanocortin system consists of alpha-MSH, agouti-related protein (AGRP), MC3R and MC4R. AGRP and alpha-MSH are believed to be the natural antagonist and agonist respectively of MC3R and MC4R. This central melanocortin system is thought to play a fundamental role in the control of feeding and body weight. Knock-out mice models and genetic studies have pointed to the importance of the melanocortins in complex human pathways such as pigmentation, lipolysis, food intake, thermogenesis, sexual behaviour, memory and inflammatory response. Recently the melanocortins and their receptors have been the target for drug-based treatment of human physiological processes. MC3R and MC4R are likely targets for controlling body weight; MCIR may be used in the treatment of inflammation and MC2R for the treatment of glucocortical deficiency. A role for MCSR still remains unclear, but the evidence suggests an exocrine gland function.
黑皮质素是一组小蛋白质激素，由阿黑皮素原（POMC）基因产物经翻译后切割产生。已知的黑皮质素激素包括α-黑素细胞刺激素（MSH）、β-MSH、γ-MSH和促肾上腺皮质激素（ACTH）。已鉴定出五种黑皮质素受体（MC1R至MC5R），其中大多数表现出组织特异性表达模式，并且对每种黑皮质素激素具有不同的结合亲和力。中枢黑皮质素系统由α-MSH、刺鼠相关蛋白（AGRP）、MC3R和MC4R组成。AGRP和α-MSH分别被认为是MC3R和MC4R的天然拮抗剂和激动剂。该中枢黑皮质素系统被认为在进食和体重控制中起基本作用。基因敲除小鼠模型和遗传学研究表明，黑皮质素在色素沉着、脂肪分解、食物摄入、产热、性行为、记忆和炎症反应等复杂的人类生理过程中具有重要作用。最近，黑皮质素及其受体已成为基于药物治疗人类生理过程的靶点。MC3R和MC4R可能是控制体重的靶点；MC1R可用于治疗炎症，MC2R可用于治疗糖皮质激素缺乏症。MCSR的作用仍不清楚，但证据表明其具有外分泌腺功能。
