Reference
Glossary
Plain-language definitions of the melanocortin terms used across the site, cross-linked to the pages that cover them in depth.
By melanocortin.com editorialLast updated 2026
A
- ACTH
- Adrenocorticotropic hormone. A POMC-derived peptide secreted by the pituitary that drives adrenal cortisol release; the only natural agonist of MC2R.
- Adenylyl cyclase
- The membrane enzyme that the melanocortin receptors switch on (via Gs) to convert ATP into the second messenger cyclic AMP.
- Afamelanotide
- A synthetic α-MSH analogue and MC1R agonist (brand Scenesse) that builds protective eumelanin; approved for erythropoietic protoporphyria.
- Agonist
- A molecule that binds a receptor and switches it on. α-MSH and ACTH are the natural melanocortin agonists.
- Agouti signalling protein (ASIP)
- An endogenous antagonist of MC1R in the skin; the mechanism behind banded ("agouti") coat colour in mammals.
- AgRP
- Agouti-related peptide. An endogenous antagonist of MC3R and MC4R, and an inverse agonist at MC4R; released by hunger-promoting neurons.
- Antagonist
- A molecule that binds a receptor and blocks an agonist without activating it. The melanocortin system is unusual in having natural antagonists (agouti, AgRP).
- Arcuate nucleus
- A hypothalamic region containing the POMC and AgRP/NPY neurons that sense leptin and set appetite via downstream MC4R neurons.
B
- Bardet–Biedl syndrome (BBS)
- A genetic ciliopathy featuring obesity, among other features; a melanocortin-pathway-related obesity indication for setmelanotide.
- Bremelanotide
- A non-selective melanocortin receptor agonist (brand Vyleesi) approved for hypoactive sexual desire disorder; acts via central MC4R circuits.
C
- cAMP
- Cyclic adenosine monophosphate. The intracellular second messenger raised by all five melanocortin receptors; activates protein kinase A.
- Cortisol
- The principal human glucocorticoid stress hormone, released from the adrenal cortex when ACTH activates MC2R.
D
- Dersimelagon
- An investigational oral, selective MC1R agonist (MT-7117) in trials for erythropoietic protoporphyria and systemic sclerosis.
E
- Erythropoietic protoporphyria (EPP)
- A rare inherited disorder in which protoporphyrin IX accumulates and makes sunlight painful; the indication for afamelanotide.
- Eumelanin
- The brown-black pigment that absorbs UV and protects DNA; favoured when MC1R signalling is strong.
F
- Familial glucocorticoid deficiency (FGD)
- An inherited failure of the adrenal cortex to make cortisol in response to ACTH; type 1 from MC2R mutations, type 2 from MRAP mutations.
G
- GPCR
- G-protein-coupled receptor. The seven-transmembrane receptor class to which all five melanocortin receptors belong.
- Gs
- The stimulatory G-protein that melanocortin receptors couple to, activating adenylyl cyclase and raising cAMP.
H
- His-Phe-Arg-Trp
- The core four-amino-acid motif (HFRW) shared by the melanocortin peptides and required for receptor binding.
- HPA axis
- The hypothalamic–pituitary–adrenal axis: the CRH → ACTH → cortisol stress circuit, whose final receptor step is MC2R.
- Hypoactive sexual desire disorder (HSDD)
- Persistent, distressing low sexual desire; bremelanotide is approved for the acquired, generalised form in premenopausal women.
I
- Inverse agonist
- A molecule that pushes a receptor below its baseline (constitutive) activity. AgRP acts this way at MC4R.
L
- Leptin
- A hormone released by fat tissue in proportion to energy stores; activates POMC neurons, feeding α-MSH into the MC4R appetite circuit.
M
- MC1R
- Melanocortin 1 receptor. On melanocytes; the switch between protective eumelanin and reddish pheomelanin.
- MC2R
- Melanocortin 2 receptor. The adrenal ACTH receptor; requires the accessory protein MRAP to function.
- MC3R
- Melanocortin 3 receptor. Hypothalamic and peripheral; governs energy partitioning and the timing of growth and puberty.
- MC4R
- Melanocortin 4 receptor. The central rheostat of appetite and body weight; the target of setmelanotide.
- MC5R
- Melanocortin 5 receptor. Regulates exocrine glands, most notably sebaceous (sebum) secretion.
- Melanin
- The pigment family produced by melanocytes, comprising eumelanin and pheomelanin.
- Melanocortin
- The family of POMC-derived peptides — α-, β-, γ-MSH and ACTH — that act on the melanocortin receptors.
- Melanocyte
- The pigment-producing skin cell on which MC1R sits and in which melanin is synthesised.
- MITF
- Microphthalmia-associated transcription factor. The master regulator of melanocyte pigment genes, driven downstream of MC1R/cAMP.
- Monogenic obesity
- Obesity caused by a single gene defect in the leptin–melanocortin pathway; MC4R mutations are the commonest such cause.
- MRAP
- Melanocortin-2-receptor accessory protein. A chaperone that escorts MC2R to the cell surface; mutations cause FGD type 2.
- MSH
- Melanocyte-stimulating hormone. The α, β, and γ melanocortin peptides cut from POMC.
P
- Paraventricular nucleus (PVN)
- The hypothalamic region densely expressing MC4R, where α-MSH and AgRP compete to set appetite.
- PCSK1
- The gene encoding prohormone convertase 1/3; deficiency disrupts POMC processing and causes early-onset obesity.
- Pheomelanin
- The reddish-yellow pigment that is a poor UV shield and can generate free radicals; favoured when MC1R signalling is weak.
- POMC
- Pro-opiomelanocortin. The single precursor protein cleaved into the melanocortin peptides (and β-endorphin).
- Prohormone convertase
- Enzymes (chiefly PC1/3 and PC2) that cut POMC at paired basic residues; their tissue distribution decides which peptides are made.
S
- Setmelanotide
- An MC4R agonist (brand Imcivree) approved for rare genetic and acquired hypothalamic obesity.
- Steroidogenesis
- The synthesis of steroid hormones such as cortisol; switched on in the adrenal cortex by ACTH acting through MC2R.
Terms link to the page that covers them in depth. Missing one?Corrections are welcome.