• Melanin-concentrating hormone (MCH), also known as pro-melanin stimulating hormone (PMCH), is a cyclic 19-amino acid orexigenic hypothalamicpeptide originally isolated from the pituitary gland of teleost fish, where it controls skin pigmentation.
  • ^{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.}
• In mammals it is involved in the regulation of feeding behavior, mood, sleep-wake cycle and energy balance.
  • ^{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.}

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 pontine reticular formation (PPRF), medial preoptic area, laterodorsal tegmental nucleus, and the olfactory tubercle.
  •  ^{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. S2CID 3644658.}
  • ^{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.} 
• MCH is activated by binding to two G-coupled protein receptors (GCPRs), MCHR1 and MCHR2.
  •  ^{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. S2CID 3644658.}
  • ^{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.}
• 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.
  • ^{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.}
• MCH is cleaved from prepro-MCH (ppMCH), a 165 amino acid polypeptide which also contains the neuropeptides GE and EI.
  •  ^{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. S2CID 3644658.}
  • ^{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.}

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.
  •  ^{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. S2CID 3644658.}
• MCH has also only been found in the medial preoptic area and the paraventricular hypothalamic nucleus during lactation.
  •  ^{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. S2CID 3644658.}

Activation and deactivation

• MCH neurons depolarize in response to high glucose concentrations.
  • ^{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. S2CID 25313032.}
• This mechanism seems to be related to glucose being used as a reactant to form ATP, which also causes MCH neurons to depolarize.
  • ^{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. S2CID 25313032.}
• The neurotransmitter, glutamate, also causes MCH neurons to depolarize, while another neurotransmitter, GABA, causes MCH neurons to hyperpolarize.
  • ^{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. S2CID 25313032.}
• Orexin also depolarizes MCH neurons.
  • ^{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. S2CID 25313032.}
• MCH neurons seems to have an inhibitory response to MCH, but does not cause the neurons to become hyperpolarized.
  • ^{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. S2CID 25313032.} 
• Norepinephrine has an inhibitory effect on MCH neurons as does acetylcholine.
  • ^{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. S2CID 25313032.} 
• MCH neurons hyperpolarize in response to serotonin.
  • ^{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. S2CID 25313032.} 
• Cannabinoids have an excitatory effect on MCH neurons.
  • ^{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. S2CID 25313032.}

• Some research has shown that dopamine has an inhibitory effect on MCH neurons, but further research is needed to fully characterize this interaction.
  • ^{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. S2CID 25313032.}

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.
  •  ^{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. S2CID 3644658.}
  • ^{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.} 
• 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.
  •  ^{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. S2CID 3644658.}
• Increased levels of MCH can also increase the amount of time spent in both REM and NREM, which in turn increases total sleep duration.
  •  ^{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. S2CID 3644658.}
• Increased levels of sugar promotes MCH and its effect on sleep and conserving energy.
  • ^{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.}

Maternal behavior

• The presence of MCH in specific locations solely during lactation is thought to help to promote maternal behavior in individuals.
  •  ^{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. S2CID 3644658.}

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

Reproduction

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

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.
  •  ^{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. PMID19442695. S2CID10189765}
• 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.
  •  ^{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. PMID19442695. S2CID10189765} 
• In melanocytes, MCH seems to have an antagonistic relationship with α-MSH, and decreased melanin production.
  •  ^{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. PMID19442695. S2CID10189765} 
• 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.
  • ^{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.}
• 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.
  • ^{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.}

Depression and anxiety

• MCH has been linked to depression and anxiety.
  • ^{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.}
  •  ^{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. PMID19442695. S2CID10189765} 
• MCHR1 antagonists have been show to act as antidepressants.
  • ^{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.}

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.
  • ^{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. S2CID 25313032.}
• 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.
  • ^{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. S2CID 25313032.}

Skin cancers

• MCH has been identified in both melanoma and squamous cell carcinoma cell lines.
  •  ^{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. PMID19442695. S2CID10189765}
• 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.
  •  ^{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. PMID19442695. S2CID10189765}
• More research is needed to fully determine and understand any relationship between MCH and possible immune responses in skin.

• MCH was initially discovered in the teleost fish; it was found to help determine the fish’s skin color. (this seems a little sparse…who? when? all that)
  • ^{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.}
  • ^{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.}
• Later, a mammalian version of MCH was discovered in rats, where most of the functions and localizations are conserved across mammalian species. (this seems a little sparse…who? when? all that)
  • ^{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.}
  • ^{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.}

History

See also

• Melanin-concentrating hormone receptor (MCHR)
• Melanin-concentrating hormone receptor 1 (MCHR1)
• Melanin-concentrating hormone receptor 2 (MCHR2)
• Orexin (OX)

External links

• Melanin-concentrating+hormone at the US National Library of Medicine Medical Subject Headings (MeSH)

Hormones

Appetite stimulants (A15)

Categories: 

• Genes on human chromosome 12
• Peptides

From Wikipedia where this page was last updated April 26, 2022