The melanocortins are a group of peptide hormones which include adrenocorticotropic hormone (ACTH) and the different forms of melanocyte-stimulating hormone (MSH), and are derived from proopiomelanocortin (POMC) in the pituitary gland. The melanocortins exert their effects by binding to and activating the melanocortin receptors.
There are 5 melanocortin receptors (MCR) and all of them are G protein–coupled receptors. In the brain, only MC3R and MC4R are expressed and their endogenous ligand is α-MSH. Agouti-related peptide (AgRP) is the endogenous antagonist.
The melanocortin system is one of the mammalian body's tools to regulate food intake in a push-pull fashion. The only neurons known to release melanocortins are located in the arcuate nucleus of the hypothalamus. Accordingly, there is a subpopulation called POMC neurons and one called AgRP neurons. When POMC neurons release α-MSH, appetite is decreased. On the other hand, when AgRP neurons release AgRP, appetite is stimulated.
Leptin, the energy surfeit hormone, and Ghrelin, the hunger hormone, are upstream regulators of the melanocortin system in the brain. These hormones also regulate the release of peptides other than the melanocortins. Disturbance of the leptin-melanocortin pathway can lead to early onset obesity as well as various metabolic disorders and suppressed immune function. 
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