| pro-opiomelanocortin | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | POMC | ||||||
| NCBI gene | 5443 | ||||||
| HGNC | 9201 | ||||||
| OMIM | 176830 | ||||||
| RefSeq | NM_000939 | ||||||
| UniProt | P01189 | ||||||
| Other data | |||||||
| Locus | Chr. 2p23 | ||||||
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| ChEMBL | |
 N Y (what is this?) (verify) | |
Themelanocyte-stimulating hormones, known collectively asMSH, also known asmelanotropins orintermedins, are a family ofpeptide hormones andneuropeptides consisting ofα-melanocyte-stimulating hormone (α-MSH),β-melanocyte-stimulating hormone (β-MSH), andγ-melanocyte-stimulating hormone (γ-MSH) that are produced by cells in thepars intermedia of theanterior lobe of the pituitary gland.
Syntheticanalogues of α-MSH, such asafamelanotide (melanotan I; Scenesse),melanotan II, andbremelanotide (PT-141), have been developed and researched.
The various forms of MSH are generated from different cleavages of theproopiomelanocortin protein, which also yields other importantneuropeptides likeadrenocorticotropic hormone.[1]: 554 [2]
Melanocytes in skin make and secrete MSH in response toultraviolet light, where it increases synthesis ofmelanin.[3]: 441 Some neurons inarcuate nucleus of thehypothalamus make and secrete α-MSH in response toleptin;[3]: 626 [4]: 419 α-MSH is also made and secreted in theanterior lobe of the pituitary gland.[5]: 1210
Acting throughmelanocortin 1 receptor, α-MSH stimulates the production and release ofmelanin (a process referred to asmelanogenesis) bymelanocytes inskin andhair.[5]: 1210
Acting in the hypothalamus, α-MSH suppresses appetite.[4]: 419 α-MSH secreted in the hypothalamus also contributes tosexual arousal.[6]
In some animals (such as the claw-toed frogXenopus laevis) production of MSH is increased when the animal is in a dark location. This causes pigment to be dispersed in pigment cells in the toad's skin, making it become darker, and harder forpredators to spot. The pigment cells are calledmelanophores and therefore, in amphibians, the hormone is often called melanophore-stimulating hormone.
An increase in MSH will cause darker skin in humans too. Pigmentation increases in humans duringpregnancy; though the exact endocrine cause is not known, α- and β-melanocyte-stimulating hormone are thought to be involved.[7]Cushing's disease due to excessadrenocorticotropic hormone (ACTH) may also result in hyperpigmentation, such asacanthosis nigricans in theaxilla. Most people with primaryAddison's disease have darkening (hyperpigmentation) of the skin, including areas not exposed to the sun; characteristic sites are skin creases (e.g. of the hands), nipple, and the inside of the cheek (buccal mucosa), new scars become hyperpigmented, whereas older ones do not darken. This occurs because MSH and ACTH share the same precursor molecule,proopiomelanocortin (POMC).
Different levels of MSH are not the major cause of variation inskin colour. However, in manyred-headed people, and other people who do nottan well, there are variations in their hormonereceptors, causing them to not respond to MSH in the blood.
The different forms of MSH belong to a group called themelanocortins. This group includes ACTH, α-MSH, β-MSH, and γ-MSH; these peptides are all cleavage products of a large precursor peptide calledproopiomelanocortin (POMC). α-MSH is the most important melanocortin for pigmentation.
The different forms of MSH have the followingamino acidsequences:
| α-MSH: | Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val |
| β-MSH (human): | Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp |
| β-MSH (porcine): | Asp-Glu-Gly-Pro-Tyr-Lys-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp |
| γ-MSH: | Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly |
Syntheticanalogues of α-MSH have been developed for human use. Two of the better known areafamelanotide (melanotan I) in testing byClinuvel Pharmaceuticals andbremelanotide byPalatin Technologies. Others includemodimelanotide andsetmelanotide.
