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'''Melanin-concentrating hormone''' ('''MCH''') is a cyclic 19-[[amino acid]] orexigenic [[hypothalamus|hypothalamic]] [[peptide]] originally isolated from the [[pituitary gland]] of [[teleost fish]] where it controls skin pigmentation.
'''Melanin-concentrating hormone''' ('''MCH''') is a cyclic 19-[[amino acid]] orexigenic [[hypothalamus|hypothalamic]] [[peptide]] originally isolated from the [[pituitary gland]] of [[teleost fish]], where it controls skin pigmentation.<ref name="Barson_2013">{{cite journal | vauthors = Barson JR, Morganstern I, Leibowitz SF | title = Complementary roles of orexin and melanin-concentrating hormone in feeding behavior | journal = International Journal of Endocrinology | volume = 2013 | pages = 983964 | date = 2013 | pmid = 23935621 | pmc = 3727095 | doi = 10.1155/2013/983964 }}</ref> In mammals it is involved in the regulation of feeding behavior, mood, sleep-wake cycle and energy balance.<ref name="Verret_2003">{{cite journal | vauthors = Verret L, Goutagny R, Fort P, Cagnon L, Salvert D, Léger L, Boissard R, Salin P, Peyron C, Luppi PH | title = A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep | journal = BMC Neuroscience | volume = 4 | issue = 19 | pages = 19 | date = September 2003 | pmid = 12964948 | pmc = 201018 | doi = 10.1186/1471-2202-4-19 }}</ref>


In mammals it is involved in the regulation of feeding behavior, mood, sleep-wake cycle<ref name="pmid12964948">{{cite journal |vauthors=Verret L, Goutagny R, Fort P, Cagnon L, Salvert D, Léger L, Boissard R, Salin P, Peyron C, Luppi PH |title=A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep |journal=BMC Neurosci |volume=4|issue=19 |year=2003 |pmid=12964948 |doi=10.1186/1471-2202-4-19 |pmc=201018 |pages=19}}</ref> and energy balance. MCH expressing neurons are located within the lateral hypothalamus and zona incerta. Despite this restricted distribution MCH neurons project widely throughout the brain. MCH knockout mice are hypophagic (eat less) and lean and are hyperactive.<ref name="pmid11867747">{{cite journal |vauthors=Marsh DJ, Weingarth DT, Novi DE, Chen HY, Trumbauer ME, Chen AS, Guan XM, Jiang MM, Feng Y, Camacho RE, Shen Z, Frazier EG, Yu H, Metzger JM, Kuca SJ, Shearman LP, Gopal-Truter S, MacNeil DJ, Strack AM, MacIntyre DE, Van der Ploeg LH, Qian S |title=Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism.|journal=Proc Natl Acad Sci USA|volume=99|issue=5|year=2002|pages=3240–5.|pmid=11867747|doi=10.1073/pnas.052706899|pmc=122503}}</ref><ref name="pmid17270288">{{cite journal |vauthors=Lalonde R, Qian S |title=Exploratory activity, motor coordination, and spatial learning in Mchr1 knockout mice. |journal=Behav Brain Res|volume=178|issue=2|year=2007|pages=293–304|pmid=17270288|doi=10.1016/j.bbr.2007.01.006}}</ref> When administered centrally it increases food intake and weight gain.
== Structure ==
 
MCH is a cyclic 19-amino acid [[neuropeptide]], as it is a polypeptide chain that is able to act as a [[neurotransmitter]]. MCH neurons are mainly concentrated in the [[lateral hypothalamic area]], [[zona incerta]], and the incerto-hypothalamic area, but they are also located, in much smaller amounts, in the paramedian potine reticular formation (PPRF), medial preoptic area, [[laterodorsal tegmental nucleus]], and the [[olfactory tubercle]].<ref name="Ferreira_2017">{{cite journal | vauthors = Ferreira JG, Bittencourt JC, Adamantidis A | title = Melanin-concentrating hormone and sleep | journal = Current Opinion in Neurobiology | volume = 44 | pages = 152–158 | date = June 2017 | pmid = 28527391 | doi = 10.1016/j.conb.2017.04.008 }}</ref><ref>{{cite journal | vauthors = Bittencourt JC | title = Anatomical organization of the melanin-concentrating hormone peptide family in the mammalian brain | journal = General and Comparative Endocrinology | volume = 172 | issue = 2 | pages = 185–97 | date = June 2011 | pmid = 21463631 | doi = 10.1016/j.ygcen.2011.03.028 }}</ref> MCH is activated by binding to two G-coupled protein receptors ([[G protein–coupled receptor|GCPR]]s), [[Melanin-concentrating hormone receptor 1|MCHR1]] and [[Melanin-concentrating hormone receptor 2|MCHR2]].<ref name="Ferreira_2017" /><ref name="Barson_2013" /> MCHR2 has only been identified in certain species such as humans, dogs, ferrets, and rhesus monkeys, while other mammals such as rodents and rabbits do not have the receptor.<ref name="Barson_2013" /> MCH is cleaved from prepro-MCH (ppMCH), a 165 amino acid polypeptide which also contains the neuropeptides GE and EI.<ref name="Ferreira_2017" /><ref name="Barson_2013" />
 
== Tissue distribution ==
MCH has also been found in peripheral structures outside of the brain. Both the spleen and [[thymus]] have shown significant levels of MCH in mammals in multiple studies. The bloodstream seems to carry MCH around the body in mammals as well, though it is a very amount in humans.{{clarification needed|date=May 2018}}
 
MCH is found in the laterodorsal tegmental nucleus solely in female brains in rat models.<ref name="Ferreira_2017" /> MCH has also only been found in the medial preoptic area and the paraventricular hypothalamic nucleus during lactation.<ref name="Ferreira_2017" />
 
== Activation and deactivation ==
MCH neurons [[Depolarization|depolarize]] in response to high glucose concentrations.<ref name="Guyon_2009">{{cite journal | vauthors = Guyon A, Conductier G, Rovere C, Enfissi A, Nahon JL | title = Melanin-concentrating hormone producing neurons: Activities and modulations | journal = Peptides | volume = 30 | issue = 11 | pages = 2031–9 | date = November 2009 | pmid = 19524001 | doi = 10.1016/j.peptides.2009.05.028 }}</ref> This mechanism seems to be related to glucose being used as a reactant to form [[Adenosine triphosphate|ATP]], which also causes MCH neurons to depolarize.<ref name="Guyon_2009" /> The neurotransmitter, [[glutamate]], also causes MCH neurons to depolarize, while another neurotransmitter, [[Gamma-Aminobutyric acid|GABA]], causes MCH neurons to [[Hyperpolarization (biology)|hyperpolarize]].<ref name="Guyon_2009" /> Orexin also depolarizes MCH neurons.<ref name="Guyon_2009" /> MCH neurons seems to have an inhibitory response to MCH, but does not cause the neurons to become hyperpolarized.<ref name="Guyon_2009" /> [[Norepinephrine]] has an inhibitory effect on MCH neurons as does [[acetylcholine]].<ref name="Guyon_2009" /> MCH neurons hyperpolarize in response to [[serotonin]].<ref name="Guyon_2009" /> Cannabinoids have an excitatory effect on MCH neurons.<ref name="Guyon_2009" />
 
Some research has shown that dopamine has an inhibitory effect on MCH neurons, but further research is needed to fully characterize this interaction.<ref name="Guyon_2009" />
 
== Function ==
 
=== Sleep ===
MCH and the hormone [[orexin]] have an antagonistic relationship with one another with regards to the sleep cycle, with orexin being almost entirely active during wake periods and MCH being more active during sleep periods.<ref name="Ferreira_2017" /><ref name="Barson_2013" /> MCH also promotes sleep, and within a sleep period increased levels of MCH seem to increase the amount of time spent in REM sleep and slow waves sleep.<ref name="Ferreira_2017" /> Increased levels of MCH can also increase the amount of time spent in both [[Rapid eye movement sleep|REM]] and [[Non-rapid eye movement sleep|NREM]], which in turn increases total sleep duration.<ref name="Ferreira_2017" /> Increased levels of sugar promotes MCH and its effect on sleep and conserving energy.<ref name="Barson_2013" />
 
=== Maternal behavior ===
The presence of MCH in specific locations solely during lactation is thought to help to promote maternal behavior in individuals.<ref name="Ferreira_2017" />
 
=== Eating behaviors and energy conservation ===
An increased presence of MCH can cause increased eating levels and has been linked to an increase in body mass.<ref name="Naufahu_2013">{{cite journal | vauthors = Naufahu J, Cunliffe AD, Murray JF | title = The roles of melanin-concentrating hormone in energy balance and reproductive function: Are they connected? | journal = Reproduction | volume = 146 | issue = 5 | pages = R141-50 | date = November 2013 | pmid = 23884861 | doi = 10.1530/REP-12-0385 }}</ref> Inversely, a decrease in the amount of MCH present can cause decreased levels in eating.<ref name="Naufahu_2013" /> Increased amounts of MCH in olfactory regions, among others, have also been linked to an increased intake of fatty foods with high caloric content.<ref name="Naufahu_2013" /><ref name="Barson_2013" /> Food that is found to taste good also seems to promote MCH, which reinforces the eating of that food.<ref name="Barson_2013" /> Sugar, specifically glucose, seems to promote MCH's role in sleep and energy conservation.<ref name="Barson_2013" /> This promoting of energy conservation has also been linked to higher body mass even when diet is controlled.<ref name="Barson_2013" /> 
 
=== Reproduction ===
It has been postulated that MCH has a modulatory role with the release of [[Luteinizing hormone|Luteinizing Hormone]] (LH) either by directly interacting acting on the pituitary gland or indirectly by affecting Gonadotropin-releasing hormone (GNRH) in the hypothalamus.<ref name="Naufahu_2013" /> [[Estrogen]] seems to be necessary in order for MCH to affect reproduction.<ref name="Naufahu_2013" />
 
=== Skin pigmentation ===
Though MCH was initially discovered for its role of determining the pigmentation in fish, trying to determine MCH's role in skin pigmentation in mammals has been much more difficult to determine.<ref name="Kemp_2009" /> However, MCHR1 has been found in human [[Melanocyte|melanocytes]] and some melanoma cells, so MCH is able to bind to these cells as well as [[Keratinocyte|keratinocytes]] though they do not express MCHR1.<ref name="Kemp_2009" /> In melanocytes, MCH seems to have an antagonistic relationship with [[Alpha-Melanocyte-stimulating hormone|α-MSH]], and decreased melanin production.<ref name="Kemp_2009" /> Though, more information is needed to fully understand MCH's relationship with skin pigmentation in mammals.
 
== Clinical significance ==
 
=== Narcolepsy ===
While MCH does promote sleep, there has been no research that links MCH to narcolepsy.<ref name="Barson_2013" /> Research has instead found that in individuals with narcolepsy there is a decrease in orexin neurons, which would promote wakefulness, while the number of MCH neurons do not vary from the average non-narcoleptic individual.<ref name="Barson_2013" />
 
=== Depression and anxiety ===
MCH has been linked to depression and anxiety.<ref name="Barson_2013" /><ref name="Kemp_2009">{{cite journal | vauthors = Kemp EH, Weetman AP | title = Melanin-concentrating hormone and melanin-concentrating hormone receptors in mammalian skin physiopathology | journal = Peptides | volume = 30 | issue = 11 | pages = 2071–5 | date = November 2009 | pmid = 19442695 | doi = 10.1016/j.peptides.2009.04.025 }}</ref> MCHR1 antagonists have been show to act as antidepressants.<ref name="Barson_2013" />
 
=== Anorexia ===
Interactions between MCH and [[Chemokine|chemokines]]/[[Cytokine|cytokines]] that lead to an overall decrease in MCH release and neuron excitability has been linked with [[Anorexia (symptom)|infection-induced anorexia]].<ref name="Guyon_2009" /> Chemokines and cytokines often appear as the result of inflammation or infection, and they can then damage MCH neurons, which can lead to anorexia in an individual.<ref name="Guyon_2009" />
 
=== Skin cancers ===
MCH has been identified in both [[melanoma]] and [[Squamous cell skin cancer|squamous cell carcinoma]] cell lines.<ref name="Kemp_2009" /> However, pro-MCH, a precursor to MCH, has not been found in melanocytes, keratinocytes, or fibroblasts, which might indicate MCH might be brought into these cells by macrophages as part of the immune response.<ref name="Kemp_2009" /> More research is needed to fully determine and understand any relationship between MCH and possible immune responses in skin.
 
== History ==
MCH was initially discovered in the teleost fish; it was found to help determine the fish's skin color.<ref name="Naufahu_2013" /><ref name="Barson_2013" /> Later, a mammalian version of MCH was discovered in rats, where most of the functions and localizations are conserved across mammalian species.<ref name="Naufahu_2013" /><ref name="Barson_2013" />


== See also ==
== See also ==
* [[Melanin-concentrating hormone receptor]] (MCHR)
* [[Melanin-concentrating hormone receptor]] (MCHR)
* [[Melanin-concentrating hormone receptor 1]] (MCHR1)
* [[Melanin-concentrating hormone receptor 2]] (MCHR2)
* [[Orexin]] (OX)


== References ==
== References ==
{{Reflist}}
{{Reflist}}
{{Refimprove|date=August 2012}}


== External links ==
== External links ==

Latest revision as of 02:15, 13 June 2018

Melanin-concentrating hormone
Identifiers
SymbolPMCH
CAS number67382-96-1
Entrez5367
HUGO9109
OMIM176795
RefSeqNM_002674
UniProtP20382
Other data
LocusChr. 12 q23.2

Melanin-concentrating hormone (MCH) is a cyclic 19-amino acid orexigenic hypothalamic peptide originally isolated from the pituitary gland of teleost fish, where it controls skin pigmentation.[1] In mammals it is involved in the regulation of feeding behavior, mood, sleep-wake cycle and energy balance.[2]

Structure

MCH is a cyclic 19-amino acid neuropeptide, as it is a polypeptide chain that is able to act as a neurotransmitter. MCH neurons are mainly concentrated in the lateral hypothalamic area, zona incerta, and the incerto-hypothalamic area, but they are also located, in much smaller amounts, in the paramedian potine reticular formation (PPRF), medial preoptic area, laterodorsal tegmental nucleus, and the olfactory tubercle.[3][4] MCH is activated by binding to two G-coupled protein receptors (GCPRs), MCHR1 and MCHR2.[3][1] MCHR2 has only been identified in certain species such as humans, dogs, ferrets, and rhesus monkeys, while other mammals such as rodents and rabbits do not have the receptor.[1] MCH is cleaved from prepro-MCH (ppMCH), a 165 amino acid polypeptide which also contains the neuropeptides GE and EI.[3][1]

Tissue distribution

MCH has also been found in peripheral structures outside of the brain. Both the spleen and thymus have shown significant levels of MCH in mammals in multiple studies. The bloodstream seems to carry MCH around the body in mammals as well, though it is a very amount in humans.[clarification needed]

MCH is found in the laterodorsal tegmental nucleus solely in female brains in rat models.[3] MCH has also only been found in the medial preoptic area and the paraventricular hypothalamic nucleus during lactation.[3]

Activation and deactivation

MCH neurons depolarize in response to high glucose concentrations.[5] This mechanism seems to be related to glucose being used as a reactant to form ATP, which also causes MCH neurons to depolarize.[5] The neurotransmitter, glutamate, also causes MCH neurons to depolarize, while another neurotransmitter, GABA, causes MCH neurons to hyperpolarize.[5] Orexin also depolarizes MCH neurons.[5] MCH neurons seems to have an inhibitory response to MCH, but does not cause the neurons to become hyperpolarized.[5] Norepinephrine has an inhibitory effect on MCH neurons as does acetylcholine.[5] MCH neurons hyperpolarize in response to serotonin.[5] Cannabinoids have an excitatory effect on MCH neurons.[5]

Some research has shown that dopamine has an inhibitory effect on MCH neurons, but further research is needed to fully characterize this interaction.[5]

Function

Sleep

MCH and the hormone orexin have an antagonistic relationship with one another with regards to the sleep cycle, with orexin being almost entirely active during wake periods and MCH being more active during sleep periods.[3][1] MCH also promotes sleep, and within a sleep period increased levels of MCH seem to increase the amount of time spent in REM sleep and slow waves sleep.[3] Increased levels of MCH can also increase the amount of time spent in both REM and NREM, which in turn increases total sleep duration.[3] Increased levels of sugar promotes MCH and its effect on sleep and conserving energy.[1]

Maternal behavior

The presence of MCH in specific locations solely during lactation is thought to help to promote maternal behavior in individuals.[3]

Eating behaviors and energy conservation

An increased presence of MCH can cause increased eating levels and has been linked to an increase in body mass.[6] Inversely, a decrease in the amount of MCH present can cause decreased levels in eating.[6] Increased amounts of MCH in olfactory regions, among others, have also been linked to an increased intake of fatty foods with high caloric content.[6][1] Food that is found to taste good also seems to promote MCH, which reinforces the eating of that food.[1] Sugar, specifically glucose, seems to promote MCH's role in sleep and energy conservation.[1] This promoting of energy conservation has also been linked to higher body mass even when diet is controlled.[1]

Reproduction

It has been postulated that MCH has a modulatory role with the release of Luteinizing Hormone (LH) either by directly interacting acting on the pituitary gland or indirectly by affecting Gonadotropin-releasing hormone (GNRH) in the hypothalamus.[6] Estrogen seems to be necessary in order for MCH to affect reproduction.[6]

Skin pigmentation

Though MCH was initially discovered for its role of determining the pigmentation in fish, trying to determine MCH's role in skin pigmentation in mammals has been much more difficult to determine.[7] However, MCHR1 has been found in human melanocytes and some melanoma cells, so MCH is able to bind to these cells as well as keratinocytes though they do not express MCHR1.[7] In melanocytes, MCH seems to have an antagonistic relationship with α-MSH, and decreased melanin production.[7] Though, more information is needed to fully understand MCH's relationship with skin pigmentation in mammals.

Clinical significance

Narcolepsy

While MCH does promote sleep, there has been no research that links MCH to narcolepsy.[1] Research has instead found that in individuals with narcolepsy there is a decrease in orexin neurons, which would promote wakefulness, while the number of MCH neurons do not vary from the average non-narcoleptic individual.[1]

Depression and anxiety

MCH has been linked to depression and anxiety.[1][7] MCHR1 antagonists have been show to act as antidepressants.[1]

Anorexia

Interactions between MCH and chemokines/cytokines that lead to an overall decrease in MCH release and neuron excitability has been linked with infection-induced anorexia.[5] Chemokines and cytokines often appear as the result of inflammation or infection, and they can then damage MCH neurons, which can lead to anorexia in an individual.[5]

Skin cancers

MCH has been identified in both melanoma and squamous cell carcinoma cell lines.[7] However, pro-MCH, a precursor to MCH, has not been found in melanocytes, keratinocytes, or fibroblasts, which might indicate MCH might be brought into these cells by macrophages as part of the immune response.[7] More research is needed to fully determine and understand any relationship between MCH and possible immune responses in skin.

History

MCH was initially discovered in the teleost fish; it was found to help determine the fish's skin color.[6][1] Later, a mammalian version of MCH was discovered in rats, where most of the functions and localizations are conserved across mammalian species.[6][1]

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 Barson JR, Morganstern I, Leibowitz SF (2013). "Complementary roles of orexin and melanin-concentrating hormone in feeding behavior". International Journal of Endocrinology. 2013: 983964. doi:10.1155/2013/983964. PMC 3727095. PMID 23935621.
  2. ↑ Verret L, Goutagny R, Fort P, Cagnon L, Salvert D, Léger L, Boissard R, Salin P, Peyron C, Luppi PH (September 2003). "A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep". BMC Neuroscience. 4 (19): 19. doi:10.1186/1471-2202-4-19. PMC 201018. PMID 12964948.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Ferreira JG, Bittencourt JC, Adamantidis A (June 2017). "Melanin-concentrating hormone and sleep". Current Opinion in Neurobiology. 44: 152–158. doi:10.1016/j.conb.2017.04.008. PMID 28527391.
  4. ↑ Bittencourt JC (June 2011). "Anatomical organization of the melanin-concentrating hormone peptide family in the mammalian brain". General and Comparative Endocrinology. 172 (2): 185–97. doi:10.1016/j.ygcen.2011.03.028. PMID 21463631.
  5. ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 Guyon A, Conductier G, Rovere C, Enfissi A, Nahon JL (November 2009). "Melanin-concentrating hormone producing neurons: Activities and modulations". Peptides. 30 (11): 2031–9. doi:10.1016/j.peptides.2009.05.028. PMID 19524001.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 Naufahu J, Cunliffe AD, Murray JF (November 2013). "The roles of melanin-concentrating hormone in energy balance and reproductive function: Are they connected?". Reproduction. 146 (5): R141–50. doi:10.1530/REP-12-0385. PMID 23884861.
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 Kemp EH, Weetman AP (November 2009). "Melanin-concentrating hormone and melanin-concentrating hormone receptors in mammalian skin physiopathology". Peptides. 30 (11): 2071–5. doi:10.1016/j.peptides.2009.04.025. PMID 19442695.

External links

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