View source for Melanocyte-stimulating hormone

{{Short description|Family of peptide hormones and neuropeptides}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox protein
| Name = [[proopiomelanocortin|pro-opiomelanocortin]]
| caption = 
| image = 
| width = 
| HGNCid = 9201
| Symbol = POMC
| AltSymbols = 
| EntrezGene = 5443
| OMIM = 176830
| RefSeq = NM_000939
| UniProt = P01189
| PDB = 
| ECnumber = 
| Chromosome = 2
| Arm = p
| Band = 23
| LocusSupplementaryData = 
}}

{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 462248095
| IUPAC_name = 
| image = α-melanocyte-stimulating_hormone.svg
| alt =
<!-- Clinical data -->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B            / C / D / X -->
| pregnancy_category = 
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = 
| routes_of_administration =
<!-- Pharmacokinetic data -->
| bioavailability = 
| protein_bound = 
| metabolism = 
| elimination_half-life = 
| excretion =
<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 9002-79-3
| ATCvet = 
| ATC_prefix = <!-- 'none' if uncategorised -->
| ATC_suffix = 
| PubChem = 
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = 
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 214332
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
}}

The '''melanocyte-stimulating hormones''', known collectively as '''MSH''', also known as '''melanotropins''' or '''intermedins''', are a family of [[peptide hormone]]s and [[neuropeptide]]s consisting of [[α-melanocyte-stimulating hormone]] (α-MSH), [[β-melanocyte-stimulating hormone]] (β-MSH), and [[γ-melanocyte-stimulating hormone]] (γ-MSH) that are produced by cells in the [[pars intermedia]] of the [[anterior lobe of the pituitary gland]].

[[Organic compound#Synthetic compounds|Synthetic]] [[analog (chemistry)|analogue]]s of α-MSH, such as [[afamelanotide]] (melanotan I; Scenesse), [[melanotan II]], and [[bremelanotide]] (PT-141), have been developed and researched.

==Biosynthesis==
The various forms of MSH are generated from different cleavages of the [[proopiomelanocortin]] protein, which also yields other important [[neuropeptides]] like [[adrenocorticotropic hormone]].<ref>{{cite book| veditors = Katzung BG, Masters SB, Trevor AJ |title=Basic & clinical pharmacology|date=2012|publisher=McGraw-Hill Medical|location=New York|isbn=978-0-07-176401-8|edition=12th}}</ref>{{rp|554}} <ref name="pmid15383650">{{cite journal | vauthors = Slominski A, Tobin DJ, Shibahara S, Wortsman J | title = Melanin pigmentation in mammalian skin and its hormonal regulation | journal = Physiological Reviews | volume = 84 | issue = 4 | pages = 1155–1228 | date = October 2004 | pmid = 15383650 | doi = 10.1152/physrev.00044.2003 }}</ref> 

[[Melanocytes]] in skin make and secrete MSH in response to [[ultraviolet]] light, where it increases synthesis of [[melanin]].<ref name=Harrisons18th>{{cite book| veditors = Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J |title=Harrison's principles of internal medicine|date=2012|publisher=McGraw-Hill|location=New York|isbn=978-0-07-174889-6|edition=18th}}</ref>{{rp|441}}  Some neurons in [[arcuate nucleus]] of the [[hypothalamus]] make and secrete α-MSH in response to [[leptin]];<ref name=Harrisons18th/>{{rp|626}}<ref name=Carlons2012>{{cite book| vauthors = Carlson NR |title=Physiology of Behavior Books a La Carte Edition.|date=2012|publisher=Pearson College Div|location=Boston|isbn=978-0-205-23981-8|edition=11th}}</ref>{{rp|419}}   α-MSH is also made and secreted in the [[Pituitary gland#Anterior 2|anterior lobe of the pituitary gland]].<ref name=Goodman12th/>{{rp|1210}}

== Function ==
Acting through [[melanocortin 1 receptor]], α-MSH stimulates the production and release of [[melanin]] (a process referred to as [[melanogenesis]]) by [[melanocyte]]s in [[skin]] and [[hair]].<ref name=Goodman12th>{{cite book| veditors = Brunton LL, Chabner BA, Knollmann BC |title=Goodman & Gilman's pharmacological basis of therapeutics.|date=2011|publisher=McGraw-Hill|location=New York|isbn=978-0-07-162442-8|edition=12th}}</ref>{{rp|1210}}

Acting in the hypothalamus, α-MSH suppresses appetite.<ref name=Carlons2012/>{{rp|419}}  α-MSH secreted in the hypothalamus also contributes to [[sexual arousal]].<ref name=King2007rev>{{cite journal | vauthors = King SH, Mayorov AV, Balse-Srinivasan P, Hruby VJ, Vanderah TW, Wessells H | title = Melanocortin receptors, melanotropic peptides and penile erection | journal = Current Topics in Medicinal Chemistry | volume = 7 | issue = 11 | pages = 1098–1106 | year = 2007 | pmid = 17584130 | pmc = 2694735 | doi = 10.2174/1568026610707011111 | author6-link = Hunter Wessells }}</ref>

===In amphibians===
In some animals (such as the claw-toed frog ''[[Xenopus 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 for [[predator]]s to spot. The pigment cells are called [[melanophores]] and therefore, in amphibians, the hormone is often called melanophore-stimulating hormone.

===In humans===
{{See also|Melanocortin receptor}}
An increase in MSH will cause darker skin in humans too. Pigmentation increases in humans during [[pregnancy]]; though the exact endocrine cause is not known, α- and β-melanocyte-stimulating hormone are thought to be involved.<ref>{{cite journal | vauthors = Motosko CC, Bieber AK, Pomeranz MK, Stein JA, Martires KJ | title = Physiologic changes of pregnancy: A review of the literature | journal = International Journal of Women's Dermatology | volume = 3 | issue = 4 | pages = 219–224 | date = December 2017 | pmid = 29234716 | pmc = 5715231 | doi = 10.1016/j.ijwd.2017.09.003 }}</ref> [[Cushing's disease]] due to excess [[adrenocorticotropic hormone]] (ACTH) may also result in hyperpigmentation, such as [[acanthosis nigricans]] in the [[axilla]]. Most people with primary [[Addison'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 in [[skin colour]]. However, in many [[red hair|red-head]]ed people, and other people who do not [[sun tan|tan]] well, there are variations in their hormone [[receptor (biochemistry)|receptor]]s, causing them to not respond to MSH in the blood.

==Structure of MSH==
{{POMC}}
The different forms of MSH belong to a group called the [[melanocortin]]s. This group includes ACTH, α-MSH, β-MSH, and γ-MSH; these peptides are all cleavage products of a large precursor peptide called [[proopiomelanocortin]] (POMC). α-MSH is the most important melanocortin for pigmentation.

The different forms of MSH have the following [[amino acid]] [[peptide sequence|sequence]]s:

{| class="wikitable"
|-
| 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
|-
|}

==Synthetic MSH==
Synthetic [[analog (chemistry)|analogue]]s of α-MSH have been developed for human use. Two of the better known are [[afamelanotide]] (melanotan I) in testing by [[Clinuvel Pharmaceuticals]] and [[bremelanotide]] by [[Palatin Technologies]]. Others include [[modimelanotide]] and [[setmelanotide]].

* [[Afamelanotide]] (brand name Scenesse) has been approved for the treatment of [[erythropoietic protoporphyria]] in [[Europe]] and is also being investigated as a method of [[photoprotection]] in the treatment of [[polymorphous light eruption]], [[actinic keratosis]] and [[squamous cell carcinoma]] (a form of [[skin cancer]]).<ref name="Clinuvel">[http://www.clinuvel.com/en/faqs/ Clinuvel FAQs] {{webarchive|url=https://web.archive.org/web/20080411022315/http://www.clinuvel.com/en/faqs/ |date=2008-04-11 }}</ref>
* An additional analogue called [[melanotan II]] causes enhanced [[libido]] and erections in most male test subjects and arousal with corresponding genital involvement in most female test subjects.<ref name=Peptides>{{cite journal | vauthors = Hadley ME | title = Discovery that a melanocortin regulates sexual functions in male and female humans | journal = Peptides | volume = 26 | issue = 10 | pages = 1687–1689 | date = October 2005 | pmid = 15996790 | doi = 10.1016/j.peptides.2005.01.023 | s2cid = 22559801 }}</ref> [[Bremelanotide]] (formerly PT-141) which stemmed from melanotan II research is currently under development for its [[aphrodisiac]] effects. These effects are mediated by actions in the hypothalamus on neurons that express [[melanocortin 3 receptor|MC<sub>3</sub>]] and [[melanocortin 4 receptor|MC<sub>4</sub> receptor]]s.

== See also ==
* [[Melanocyte-inhibiting factor]]
* [[Agouti-related peptide]]
* [[Agouti signalling peptide]]
* [[Nelson's syndrome]]

== References ==
{{Reflist|2}}

== Further reading ==
* {{cite journal | vauthors = Millington GW | title = Proopiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors | journal = Clinical and Experimental Dermatology | volume = 31 | issue = 3 | pages = 407–412 | date = May 2006 | pmid = 16681590 | doi = 10.1111/j.1365-2230.2006.02128.x | s2cid = 25213876 }}
* {{cite journal | vauthors = Millington GW | title = The role of proopiomelanocortin (POMC) neurones in feeding behaviour | journal = Nutrition & Metabolism | volume = 4 | pages = 18 | date = September 2007 | pmid = 17764572 | pmc = 2018708 | doi = 10.1186/1743-7075-4-18 | doi-access = free }}

== External links ==
* {{MeshName|Melanocyte-Stimulating+Hormones}}

{{Hormones}}
{{Neuropeptides}}
{{Melanocortin receptor modulators}}
{{Authority control}}

[[Category:Amphibian hormones]]
[[Category:Anterior pituitary hormones]]
[[Category:Human hormones]]
[[Category:Melanocortin receptor agonists]]
[[Category:Peptide hormones]]
[[Category:Stimulating hormones]]