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. 
- Gantz I, Fong TM (March 2003). "The melanocortin system". American Journal of Physiology. Endocrinology and Metabolism. 284 (3): E468–74. doi:10.1152/ajpendo.00434.2002. PMID 12556347.
- Raffin-Sanson ML, de Keyzer Y, Bertagna X (August 2003). "Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions". European Journal of Endocrinology. 149 (2): 79–90. doi:10.1530/eje.0.1490079. PMID 12887283.
- Yoon YR, Baik JH (December 2015). "Melanocortin 4 Receptor and Dopamine D2 Receptor Expression in Brain Areas Involved in Food Intake". Endocrinology and Metabolism. 30 (4): 576–83. doi:10.3803/enm.2015.30.4.576. PMC 4722414. PMID 26790386.
- Zhou Y, Rui L (June 2013). "Leptin signaling and leptin resistance". Frontiers of Medicine. 7 (2): 207–22. doi:10.1007/s11684-013-0263-5. PMC 4069066. PMID 23580174.
- Klok MD, Jakobsdottir S, Drent ML (January 2007). "The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review". Obesity Reviews. 8 (1): 21–34. doi:10.1111/j.1467-789x.2006.00270.x. PMID 17212793. S2CID 24266123.
- Nunziata A, Borck G, Funcke JB, Kohlsdorf K, Brandt S, Hinney A, Moepps B, Gierschik P, Debatin KM, Fischer-Posovszky P, Wabitsch M (November 2017). "Estimated prevalence of potentially damaging variants in the leptin gene". Molecular and Cellular Pediatrics. 4 (1): 10. doi:10.1186/s40348-017-0074-x. PMC 5670095. PMID 29101506.