Melanocyte-stimulating hormone: Difference between revisions

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{{protein
{{Infobox protein
| Name = proopiomelanocortin (adrenocorticotropin/ beta-lipotropin/ alpha-melanocyte stimulating hormone/ beta-melanocyte stimulating hormone/ beta-endorphin)
| Name = [[proopiomelanocortin|pro-opiomelanocortin]]
| caption =  
| caption =  
| image =  
| image =  
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| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
}}
{{SI}}
{{CMG}}
__NOTOC__


{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 462248095
| IUPAC_name =
| image =
| 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 =
| 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.


==Overview==
==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|editor1-last=Katzung|editor1-first=Bertram G.|editor2-last=Masters|editor2-first=Susan B.|editor3-last=Trevor|editor3-first=Anthony J.|title=Basic & clinical pharmacology|date=2012|publisher=McGraw-Hill Medical|location=New York|isbn=978-0-07-176401-8|edition=12th}}</ref>{{rp|554}}


The '''melanocyte-stimulating hormones''' (collectively referred to as '''MSH''') are a class of [[peptide hormone]]s produced by cells in the [[intermediate lobe]] of the [[pituitary gland]].  
[[Keratinocytes]] in skin make and secrete MSH in response to [[ultraviolet]] light, where it increases synthesis of [[melanin]].<ref name=Harrisons18th>{{cite book|editor1-last=Longo|editor1-first=Dan L.|editor2-last=Fauci|editor2-first=Anthony S.|editor3-last=Kasper|editor3-first=Dennis L.|editor4-last=Hauser|editor4-first=Stephen L.|editor5-last=Jameson|editor5-first=J. Larry|editor6-last=Loscalzo|editor6-first=Joseph|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|last1=Carlson|first1=Neil R.|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==
==Function==
They stimulate the production and release of [[melanin]] ([[melanogenesis]]) by [[melanocyte]]s in [[skin]] and [[hair]]. MSH is also produced by a subpopulation of neurons in the [[arcuate nucleus]] of the [[hypothalamus]]. MSH released into the brain by these neurons has effects on appetite and sexual arousal.  
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|editor1-last=Brunton|editor1-first=Laurence L.|editor2-last=Chabner|editor2-first=Bruce A.|editor3-last=Knollmann|editor3-first=Björn C.|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>{{vcite2 journal | vauthors = King SH, Mayorov AV, Balse-Srinivasan P, Hruby VJ, Vanderah TW, Wessells H | title = Melanocortin receptors, melanotropic peptides and penile erection | journal = Curr Top Med Chem | volume = 7 | issue = 11 | pages = 1098–1106 | year = 2007 | pmid = 17584130 | pmc = 2694735 | doi = 10.2174/1568026610707011111}}</ref>


===In amphibians===
===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 predators to spot. The pigment cells are called melanophores and therefore, in amphibians, the hormone is often called melanophore-stimulating hormone.
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===
===In humans===
An increase in MSH will cause a darkening in humans too. Melanocyte-stimulating hormone increases in humans during [[pregnancy]]. This, along with increased [[estrogen]]s, causes increased pigmentation in pregnant women. In Addison's disease high levels of [[adrenocorticotropic hormone]] (ACTH) production also leads to high MSH levels, which cause an abnormal darkening.
{{See also|Melanocortin receptor}}
An increase in MSH will cause darker skin in humans too. MSH increases in humans during [[pregnancy]]. This, along with increased [[estrogen]]s, causes increased pigmentation in pregnant women. 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 racial variation in skin colour. In many red headed people, and other people who do not tan well, there are variations in their hormone [[receptor (biochemistry)|receptor]]s, causing them to not respond to MSH in the blood.
Different levels of MSH are not the major cause of racial 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==
==Structure of MSH==
Melanocyte-stimulating hormone belongs to a group called the [[melanocortin]]s. This group includes ACTH, alpha-MSH, beta-MSH and gamma-MSH; these peptides are all cleavage products of a large precursor peptide called [[pro-opiomelanocortin ]](POMC). Alpha-MSH is the most important melanocortin for pigmentation.
{{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:


The different melanocyte-stimulating hormones have the following [[amino acid]] [[Peptide sequence|sequence]]s:
{| class="wikitable"
{| class="wikitable"
|-
|-
| alpha-MSH: || Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH<sub>2</sub>
| α-MSH: || Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val
|-
|-
| beta-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 (human): || Ala-Glu-Lys-Lys-Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp
|-
|-
| beta-MSH (porcine): || Asp-Glu-Gly-Pro-Tyr-Lys-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
|-
|-
| gamma-MSH: || Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly
| γ-MSH: || Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly
|-
|-
|}
|}


==Synthetic MSH==
==Synthetic MSH==
Two synthetic [[Analog (chemistry)|analogs]] of alpha-MSH, based upon a peptide called [[Melanotan]] are being developed for human use, one by an [[Australia]]n company the other by a New Jersey company.  
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]</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 |author=Hadley ME |title=Discovery that a melanocortin regulates sexual functions in male and female humans |journal=Peptides |volume=26 |issue=10 |pages=1687–9 |date=Oct 2005 |pmid=15996790 |doi=10.1016/j.peptides.2005.01.023 }}</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.


* Alpha-MSH topical cream is being investigated as a possible therapeutic aid in the treatment of [[melanoma]].
==See also==
* [[Melanocyte-inhibiting factor]]
* [[Agouti-related peptide]]
* [[Agouti signalling peptide]]
* [[Nelson's syndrome]]


* An additional analog called Melanotan II causes enhanced [[libido]] and erections in most male test subject and arousal with corresponding genital involvement in most female test subjects. [[Bremelanotide]] (formerly PT-141) the peptide that is being developed by the New Jersey company is a close analog of melanotan II that shares its [[aphrodisiac]] effects and is currently in clinical trials to treat [[erectile dysfunction]] and sexual arousal disorder. These effects are mediated by actions in the hypothalamus on neurons that express MC3 {{Gene|MC3R}} and MC4 {{Gene|MC4R}} receptors.
==References==
{{Reflist|2}}
 
==Further reading==
* {{cite journal | author = Millington GW | title = Proopiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors | journal = Clin. Exp. Dermatol. | volume = 31 | issue = 3 | pages = 407–12 |date=May 2006 | pmid = 16681590 | doi = 10.1111/j.1365-2230.2006.02128.x | url =  }}
* {{cite journal | author = Millington GW | title = The role of proopiomelanocortin (POMC) neurones in feeding behaviour | journal = Nutr Metab (Lond) | volume = 4 | issue = | pages = 18 | year = 2007 | pmid = 17764572 | pmc = 2018708 | doi = 10.1186/1743-7075-4-18 | url =  }}


==External links==
==External links==
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{{Hormones}}
{{Hormones}}
{{Neuropeptides}}
{{Neuropeptides}}
{{Melanocortin receptor modulators}}
[[Category:Amphibian hormones]]
[[Category:Anterior pituitary hormones]]
[[Category:Human hormones]]
[[Category:Melanocortin receptor agonists]]
[[Category:Peptide hormones]]
[[Category:Peptide hormones]]
[[Category:Anterior pituitary hormones]]
[[Category:Endocrinology]]
[[de:Melanozyten-stimulierendes Hormon]]
[[es:Melanotropina]]
[[fr:Hormone mélanotrope]]
[[he:MSH]]
[[mk:Меланотропин]]
[[nl:Melanocyt-stimulerend hormoon]]
[[pl:Melanotropina]]
[[ru:Меланоцитстимулирующие гормоны]]
[[sk:Melanotropín]]
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Revision as of 15:10, 23 October 2017

pro-opiomelanocortin
Identifiers
SymbolPOMC
Entrez5443
HUGO9201
OMIM176830
RefSeqNM_000939
UniProtP01189
Other data
LocusChr. 2 p23
Melanocyte-stimulating hormone
Identifiers
ChemSpider
  • none
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
 ☒N☑Y (what is this?)  (verify)

The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and neuropeptides 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.

Synthetic analogues 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.[1]:554

Keratinocytes in skin make and secrete MSH in response to ultraviolet light, where it increases synthesis of melanin.[2]:441 Some neurons in arcuate nucleus of the hypothalamus make and secrete α-MSH in response to leptin;[2]:626[3]:419 α-MSH is also made and secreted in the anterior lobe of the pituitary gland.[4]:1210

Function

Acting through melanocortin 1 receptor, α-MSH stimulates the production and release of melanin (a process referred to as melanogenesis) by melanocytes in skin and hair.[4]:1210

Acting in the hypothalamus, α-MSH suppresses appetite.[3]:419 α-MSH secreted in the hypothalamus also contributes to sexual arousal.[5]

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 predators 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. MSH increases in humans during pregnancy. This, along with increased estrogens, causes increased pigmentation in pregnant women. 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 racial variation in skin colour. However, in many red-headed people, and other people who do not tan well, there are variations in their hormone receptors, causing them to not respond to MSH in the blood.

Structure of MSH

proopiomelanocortin derivatives
POMC
     
γ-MSH ACTH β-lipotropin
         
  α-MSH CLIP γ-lipotropin β-endorphin
       
    β-MSH  

The different forms of MSH belong to a group called the melanocortins. 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 sequences:

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 analogues 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.

See also

References

  1. ↑ Katzung, Bertram G.; Masters, Susan B.; Trevor, Anthony J., eds. (2012). Basic & clinical pharmacology (12th ed.). New York: McGraw-Hill Medical. ISBN 978-0-07-176401-8.
  2. ↑ 2.0 2.1 Longo, Dan L.; Fauci, Anthony S.; Kasper, Dennis L.; Hauser, Stephen L.; Jameson, J. Larry; Loscalzo, Joseph, eds. (2012). Harrison's principles of internal medicine (18th ed.). New York: McGraw-Hill. ISBN 978-0-07-174889-6.
  3. ↑ 3.0 3.1 Carlson, Neil R. (2012). Physiology of Behavior Books a La Carte Edition (11th ed.). Boston: Pearson College Div. ISBN 978-0-205-23981-8.
  4. ↑ 4.0 4.1 Brunton, Laurence L.; Chabner, Bruce A.; Knollmann, Björn C., eds. (2011). Goodman & Gilman's pharmacological basis of therapeutics (12th ed.). New York: McGraw-Hill. ISBN 978-0-07-162442-8.
  5. ↑ King SH, Mayorov AV, Balse-Srinivasan P, Hruby VJ, Vanderah TW, Wessells H (2007). "Melanocortin receptors, melanotropic peptides and penile erection". Curr Top Med Chem. 7 (11): 1098–1106. doi:10.2174/1568026610707011111. PMC 2694735. PMID 17584130.
  6. ↑ Clinuvel FAQs
  7. ↑ Hadley ME (Oct 2005). "Discovery that a melanocortin regulates sexual functions in male and female humans". Peptides. 26 (10): 1687–9. doi:10.1016/j.peptides.2005.01.023. PMID 15996790.

Further reading

External links

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