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Gene Review

PMCH  -  pro-melanin-concentrating hormone

Homo sapiens

Synonyms: MCH, Pro-MCH
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Disease relevance of PMCH


Psychiatry related information on PMCH


High impact information on PMCH

  • Here we show that SNAP-7941, a selective, high-affinity MCH1 receptor (MCH1-R) antagonist, inhibited food intake stimulated by central administration of MCH, reduced consumption of palatable food, and, after chronic administration to rats with diet-induced obesity, resulted in a marked, sustained decrease in body weight [8].
  • Melanin concentrating hormone (MCH) is an orexigenic hypothalamic neuropeptide, which plays an important role in the complex regulation of energy balance and body weight [8].
  • First, MCH stimulates feeding when injected directly into rat brains; second, the messenger RNA for the MCH precursor is upregulated in the hypothalamus of genetically obese mice and in fasted animals; and third, mice lacking MCH eat less and are lean [9].
  • MCH antagonists might, therefore, provide a treatment for obesity [9].
  • Here we show that the 353-amino-acid human orphan G-protein-coupled receptor SLC-1 expressed in HEK293 cells binds MCH with sub-nanomolar affinity, and is stimulated by MCH to mobilize intracellular Ca2+ and reduce forskolin-elevated cyclic AMP levels [9].

Chemical compound and disease context of PMCH


Biological context of PMCH


Anatomical context of PMCH

  • A panel of somatic cell hybrids segregating either human or rat chromosomes was used to determine the chromosomal localization of the PMCH locus [14].
  • Melanin-concentrating hormone (MCH) is a peptide that has been isolated from salmon pituitary and rat hypothalamus [2].
  • When expressed in Chinese hamster ovary (CHO) cells, the S643b receptor displays a strong, dose-dependent, transient elevation of intracellular calcium in response to MCH (EC(50) = 9.5 nM) [15].
  • Stimulation of cultured human melanocytes with MCH reduced the alpha-MSH-induced increase in cAMP production [16].
  • In the human hypothalamus, neuronal cell bodies stained for MCH were observed only in the periventricular area whereas cell bodies containing alpha-MSH were exclusively located in the infundibular (arcuate) nucleus [17].

Associations of PMCH with chemical compounds

  • MCH-2R displayed high-affinity MCH binding, resulting in inositol phosphate turnover and release of intracellular calcium in mammalian cells [11].
  • HEK293 cells transfected with MCH(2) receptors responded to nanomolar concentrations of MCH with an increase in intracellular Ca(2+) levels and increased cellular extrusion of protons [18].
  • Furthermore, sequence identities, with perhaps functional implications, were found among the MCH, human ANF, and aplysia peptide A hormone precursors [19].
  • Using HEK293 cells stably expressing MCHR1, we demonstrate that MCH, acting through MCHR1, antagonizes the action of forskolin, an adenylate cyclase activator that increases intracellular levels of cAMP [20].
  • Competition binding experiments with both MCHR isoforms, a series of previously characterized alanine scan MCH analogues, and a recently identified nonpeptide MCHR1-selective antagonist T-226296 confirmed the expected receptor selectivity [21].

Physical interactions of PMCH


Regulatory relationships of PMCH

  • MCHR2 is specifically activated by nanomolar concentrations of MCH, binds to MCH with high affinity, and signals through Gq protein [1].
  • Melanin-concentrating hormone (MCH) is a neuropeptide highly expressed in the brain that regulates several physiological functions mediated by receptors in the G protein-coupled receptor family [25].
  • In fishes, MCH induces melanin concentration within the melanophores and may inhibit ACTH secretion [26].
  • [Ala(14)]-MCH was equipotent to native MCH in its ability to bind to and activate the wild-type MCH receptor, whereas [Ala(11)]-MCH displayed a 3000-fold reduction in binding affinity and a complete loss of measurable functional activity [27].
  • However, in the mPOA, the action of MCH was blocked only by the MC5-R antagonist [28].

Other interactions of PMCH

  • Recently, several groups reported the identification of an orphan G protein-coupled receptor as a receptor for MCH (MCH-1R) [11].
  • Assignment of the human pro-melanin-concentrating hormone gene (PMCH) to chromosome 12q23-q24 and two variant genes (PMCH1 and PMCHL2) to chromosome 5p14 and 5q12-q13 [2].
  • The characterization of a second mammalian G protein-coupled receptor for MCH potentially indicates that the control of energy homeostasis in mammals by the MCH neuropeptide system may be more complex than initially anticipated [11].
  • In eight healthy, normal weight men, we measured serum MCH, AGRP, and alpha-MSH levels at baseline, after 2 d of fasting alone (a low leptin state), and after 2 d of fasting with replacement dose recombinant methionyl human leptin (r-metHuLeptin) administration to normalize circulating leptin levels [29].
  • These findings suggest that serum MCH and possibly AGRP levels could serve as useful peripheral markers of changes in energy homeostasis and thus merit additional investigation [29].

Analytical, diagnostic and therapeutic context of PMCH


  1. Identification and characterization of a melanin-concentrating hormone receptor. An, S., Cutler, G., Zhao, J.J., Huang, S.G., Tian, H., Li, W., Liang, L., Rich, M., Bakleh, A., Du, J., Chen, J.L., Dai, K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  2. Assignment of the human pro-melanin-concentrating hormone gene (PMCH) to chromosome 12q23-q24 and two variant genes (PMCH1 and PMCHL2) to chromosome 5p14 and 5q12-q13. Pedeutour, F., Szpirer, C., Nahon, J.L. Genomics (1994) [Pubmed]
  3. Melanin-concentrating hormone receptor mutations and human obesity: functional analysis. Gibson, W.T., Pissios, P., Trombly, D.J., Luan, J., Keogh, J., Wareham, N.J., Maratos-Flier, E., O'Rahilly, S., Farooqi, I.S. Obes. Res. (2004) [Pubmed]
  4. Characterization of a neuronal cell line expressing native human melanin-concentrating hormone receptor 1 (MCHR1). Fry, D., Dayton, B., Brodjian, S., Ogiela, C., Sidorowicz, H., Frost, L.J., McNally, T., Reilly, R.M., Collins, C.A. Int. J. Biochem. Cell Biol. (2006) [Pubmed]
  5. Endogenous melanin-concentrating hormone receptor SLC-1 in human melanoma SK-MEL-37 cells. Saito, Y., Wang, Z., Hagino-Yamagishi, K., Civelli, O., Kawashima, S., Maruyama, K. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  6. The regulation of alcohol intake by melanin-concentrating hormone in rats. Duncan, E.A., Rider, T.R., Jandacek, R.J., Clegg, D.J., Benoit, S.C., Tso, P., Woods, S.C. Pharmacol. Biochem. Behav. (2006) [Pubmed]
  7. Central administration of melanin-concentrating hormone (MCH) suppresses food intake, but not locomotor activity, in the goldfish, Carassius auratus. Matsuda, K., Shimakura, S., Maruyama, K., Miura, T., Uchiyama, M., Kawauchi, H., Shioda, S., Takahashi, A. Neurosci. Lett. (2006) [Pubmed]
  8. Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Borowsky, B., Durkin, M.M., Ogozalek, K., Marzabadi, M.R., DeLeon, J., Lagu, B., Heurich, R., Lichtblau, H., Shaposhnik, Z., Daniewska, I., Blackburn, T.P., Branchek, T.A., Gerald, C., Vaysse, P.J., Forray, C. Nat. Med. (2002) [Pubmed]
  9. Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1. Chambers, J., Ames, R.S., Bergsma, D., Muir, A., Fitzgerald, L.R., Hervieu, G., Dytko, G.M., Foley, J.J., Martin, J., Liu, W.S., Park, J., Ellis, C., Ganguly, S., Konchar, S., Cluderay, J., Leslie, R., Wilson, S., Sarau, H.M. Nature (1999) [Pubmed]
  10. Rheological properties of erythrocytes in patients suffering from erysipelas. Examination with LORCA device. Biesiada, G., Krzemień, J., Czepiel, J., Teległów, A., Dabrowski, Z., Spodaryk, K., Mach, T. Clin. Hemorheol. Microcirc. (2006) [Pubmed]
  11. Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R. Sailer, A.W., Sano, H., Zeng, Z., McDonald, T.P., Pan, J., Pong, S.S., Feighner, S.D., Tan, C.P., Fukami, T., Iwaasa, H., Hreniuk, D.L., Morin, N.R., Sadowski, S.J., Ito, M., Ito, M., Bansal, A., Ky, B., Figueroa, D.J., Jiang, Q., Austin, C.P., MacNeil, D.J., Ishihara, A., Ihara, M., Kanatani, A., Van der Ploeg, L.H., Howard, A.D., Liu, Q. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  12. T-226296: a novel, orally active and selective melanin-concentrating hormone receptor antagonist. Takekawa, S., Asami, A., Ishihara, Y., Terauchi, J., Kato, K., Shimomura, Y., Mori, M., Murakoshi, H., Kato, K., Suzuki, N., Nishimura, O., Fujino, M. Eur. J. Pharmacol. (2002) [Pubmed]
  13. SVK14 cells express an MCH binding site different from the MCH1 or MCH2 receptor. Audinot, V., Lahaye, C., Suply, T., Rovère-Jovène, C., Rodriguez, M., Nicolas, J.P., Beauverger, P., Cardinaud, B., Galizzi, J.P., Fauchère, J.L., Nahon, J.L., Boutin, J.A. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  14. Pro-melanin-concentrating hormone gene (PMCH) is localized on human chromosome 12q and rat chromosome 7. Nahon, J.L., Joly, C., Levan, G., Szpirer, J., Szpirer, C. Genomics (1992) [Pubmed]
  15. Cloning and molecular characterization of the novel human melanin-concentrating hormone receptor MCH2. Rodriguez, M., Beauverger, P., Naime, I., Rique, H., Ouvry, C., Souchaud, S., Dromaint, S., Nagel, N., Suply, T., Audinot, V., Boutin, J.A., Galizzi, J.P. Mol. Pharmacol. (2001) [Pubmed]
  16. Melanin-concentrating hormone and its receptor are expressed and functional in human skin. Hoogduijn, M.J., Ancans, J., Suzuki, I., Estdale, S., Thody, A.J. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  17. Melanin-concentrating hormone (MCH) is colocalized with alpha-melanocyte-stimulating hormone (alpha-MSH) in the rat but not in the human hypothalamus. Pelletier, G., Guy, J., Désy, L., Li, S., Eberle, A.N., Vaudry, H. Brain Res. (1987) [Pubmed]
  18. Molecular cloning and functional characterization of MCH2, a novel human MCH receptor. Hill, J., Duckworth, M., Murdock, P., Rennie, G., Sabido-David, C., Ames, R.S., Szekeres, P., Wilson, S., Bergsma, D.J., Gloger, I.S., Levy, D.S., Chambers, J.K., Muir, A.I. J. Biol. Chem. (2001) [Pubmed]
  19. Structure of the human melanin concentrating hormone mRNA. Presse, F., Nahon, J.L., Fischer, W.H., Vale, W. Mol. Endocrinol. (1990) [Pubmed]
  20. Melanin-concentrating hormone receptor 1 activates extracellular signal-regulated kinase and synergizes with G(s)-coupled pathways. Pissios, P., Trombly, D.J., Tzameli, I., Maratos-Flier, E. Endocrinology (2003) [Pubmed]
  21. Europium-labeled melanin-concentrating hormone analogues: ligands for measuring binding to melanin-concentrating hormone receptors 1 and 2. Gao, X., Hsu, C.K., Heinz, L.J., Morin, J., Shi, Y., Shukla, N.K., Smiley, D.L., Xu, J., Zhong, B., Slieker, L.J. Anal. Biochem. (2004) [Pubmed]
  22. Birth of two chimeric genes in the Hominidae lineage. Courseaux, A., Nahon, J.L. Science (2001) [Pubmed]
  23. Association analyses suggest GPR24 as a shared susceptibility gene for bipolar affective disorder and schizophrenia. Severinsen, J.E., Als, T.D., Binderup, H., Kruse, T.A., Wang, A.G., Vang, M., Muir, W.J., Blackwood, D.H., Mors, O., Børglum, A.D. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2006) [Pubmed]
  24. The melanin-concentrating hormone receptor 1, a novel target of autoantibody responses in vitiligo. Kemp, E.H., Waterman, E.A., Hawes, B.E., O'Neill, K., Gottumukkala, R.V., Gawkrodger, D.J., Weetman, A.P., Watson, P.F. J. Clin. Invest. (2002) [Pubmed]
  25. Identification and pharmacological characterization of a novel human melanin-concentrating hormone receptor, mch-r2. Wang, S., Behan, J., O'Neill, K., Weig, B., Fried, S., Laz, T., Bayne, M., Gustafson, E., Hawes, B.E. J. Biol. Chem. (2001) [Pubmed]
  26. Isolation and characterization of the human melanin-concentrating hormone gene and a variant gene. Breton, C., Schorpp, M., Nahon, J.L. Brain Res. Mol. Brain Res. (1993) [Pubmed]
  27. Molecular characterization of the melanin-concentrating hormone/receptor complex: identification of critical residues involved in binding and activation. Macdonald, D., Murgolo, N., Zhang, R., Durkin, J.P., Yao, X., Strader, C.D., Graziano, M.P. Mol. Pharmacol. (2000) [Pubmed]
  28. Evidence for a stimulatory action of melanin-concentrating hormone on luteinising hormone release involving MCH1 and melanocortin-5 receptors. Murray, J.F., Hahn, J.D., Kennedy, A.R., Small, C.J., Bloom, S.R., Haskell-Luevano, C., Coen, C.W., Wilson, C.A. J. Neuroendocrinol. (2006) [Pubmed]
  29. Circulating melanin-concentrating hormone, agouti-related protein, and alpha-melanocyte-stimulating hormone levels in relation to body composition: alterations in response to food deprivation and recombinant human leptin administration. Gavrila, A., Chan, J.L., Miller, L.C., Heist, K., Yiannakouris, N., Mantzoros, C.S. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
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