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Gene Review

Pmch  -  pro-melanin-concentrating hormone

Mus musculus

Synonyms: A230109K23Rik, MCH, Mch, Pro-MCH, melanin-concentrating hormone
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Disease relevance of Pmch

  • Transgenic mice overexpressing Pmch are hyperphagic and develop mild obesity [1].
  • Animals treated with MCH develop hyperphagia and obesity [2].
  • Therefore, MCH and ORX neurons may regulate both cognitive and autonomic aspects of food intake and body weight regulation [3].
  • As MCH has been implicated in E2-induced hypophagia, we performed E2 pellet implantation in MCH knockout mice and observed hypophagia and weight loss, indicating that MCH is not an essential mediator of E2-induced anorexia [4].
  • Mice treated via intracerebroventricular infusion with MCH, or that overexpress MCH or MCHR1, exhibit weight gain compared with control animals [5].

Psychiatry related information on Pmch


High impact information on Pmch

  • However, M3R-/- mice remained responsive to the orexigenic effects of MCH [9].
  • Our results show that MCH is a critical regulator of feeding and energy balance which acts downstream of leptin and the melanocortin system, and that deletion of a gene encoding a single orexigenic peptide can result in leanness [10].
  • Neurons containing MCH are located in the zona incerta and in the lateral hypothalamus [11].
  • These findings suggest that MCH participates in the hypothalamic regulation of body weight [11].
  • To determine whether MCH is involved in the regulation of feeding, we injected MCH into the lateral ventricles of rats and found that their food consumption increased [11].

Chemical compound and disease context of Pmch

  • This compound was found to be a high-affinity ligand for MCHr1 and a potent inhibitor of MCH-mediated Ca(2+) release, showed good plasma and CNS exposure upon oral dosing in diet-induced obese mice, and is the first reported MCHr1 antagonist that is efficacious upon oral dosing in a chronic model of weight loss [12].
  • In order to improve both quantitative and qualitative thalassemia erythropoiesis, several trials were undertaken combining rHuEPO with hydroxyurea (HU), which is known to increase % Hb F, MCV and MCH without a major effect on Hb levels [13].

Biological context of Pmch


Anatomical context of Pmch


Associations of Pmch with chemical compounds


Regulatory relationships of Pmch


Other interactions of Pmch


Analytical, diagnostic and therapeutic context of Pmch


  1. Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Marsh, D.J., Weingarth, D.T., Novi, D.E., Chen, H.Y., Trumbauer, M.E., Chen, A.S., Guan, X.M., Jiang, M.M., Feng, Y., Camacho, R.E., Shen, Z., Frazier, E.G., Yu, H., Metzger, J.M., Kuca, S.J., Shearman, L.P., Gopal-Truter, S., MacNeil, D.J., Strack, A.M., MacIntyre, D.E., Van der Ploeg, L.H., Qian, S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype. Segal-Lieberman, G., Bradley, R.L., Kokkotou, E., Carlson, M., Trombly, D.J., Wang, X., Bates, S., Myers, M.G., Flier, J.S., Maratos-Flier, E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  3. Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. Elias, C.F., Saper, C.B., Maratos-Flier, E., Tritos, N.A., Lee, C., Kelly, J., Tatro, J.B., Hoffman, G.E., Ollmann, M.M., Barsh, G.S., Sakurai, T., Yanagisawa, M., Elmquist, J.K. J. Comp. Neurol. (1998) [Pubmed]
  4. Estradiol-induced anorexia is independent of leptin and melanin-concentrating hormone. Tritos, N.A., Segal-Lieberman, G., Vezeridis, P.S., Maratos-Flier, E. Obes. Res. (2004) [Pubmed]
  5. Biological examination of melanin concentrating hormone receptor 1: multi-tasking from the hypothalamus. Rokosz, L.L., Hobbs, D.W. Drug News Perspect. (2006) [Pubmed]
  6. The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus accumbens to modulate feeding behavior and forced-swim performance. Georgescu, D., Sears, R.M., Hommel, J.D., Barrot, M., Bolaños, C.A., Marsh, D.J., Bednarek, M.A., Bibb, J.A., Maratos-Flier, E., Nestler, E.J., DiLeone, R.J. J. Neurosci. (2005) [Pubmed]
  7. Enhanced running wheel activity of both Mch1r- and Pmch-deficient mice. Zhou, D., Shen, Z., Strack, A.M., Marsh, D.J., Shearman, L.P. Regul. Pept. (2005) [Pubmed]
  8. Lack of efficacy of melanin-concentrating hormone-1 receptor antagonists in models of depression and anxiety. Basso, A.M., Bratcher, N.A., Gallagher, K.B., Cowart, M.D., Zhao, C., Sun, M., Esbenshade, T.A., Brune, M.E., Fox, G.B., Schmidt, M., Collins, C.A., Souers, A.J., Iyengar, R., Vasudevan, A., Kym, P.R., Hancock, A.A., Rueter, L.E. Eur. J. Pharmacol. (2006) [Pubmed]
  9. Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean. Yamada, M., Miyakawa, T., Duttaroy, A., Yamanaka, A., Moriguchi, T., Makita, R., Ogawa, M., Chou, C.J., Xia, B., Crawley, J.N., Felder, C.C., Deng, C.X., Wess, J. Nature (2001) [Pubmed]
  10. Mice lacking melanin-concentrating hormone are hypophagic and lean. Shimada, M., Tritos, N.A., Lowell, B.B., Flier, J.S., Maratos-Flier, E. Nature (1998) [Pubmed]
  11. A role for melanin-concentrating hormone in the central regulation of feeding behaviour. Qu, D., Ludwig, D.S., Gammeltoft, S., Piper, M., Pelleymounter, M.A., Cullen, M.J., Mathes, W.F., Przypek, R., Kanarek, R., Maratos-Flier, E. Nature (1996) [Pubmed]
  12. Identification of 2-(4-benzyloxyphenyl)-N- [1-(2-pyrrolidin-1-yl-ethyl)-1H-indazol-6-yl]acetamide, an orally efficacious melanin-concentrating hormone receptor 1 antagonist for the treatment of obesity. Souers, A.J., Gao, J., Brune, M., Bush, E., Wodka, D., Vasudevan, A., Judd, A.S., Mulhern, M., Brodjian, S., Dayton, B., Shapiro, R., Hernandez, L.E., Marsh, K.C., Sham, H.L., Collins, C.A., Kym, P.R. J. Med. Chem. (2005) [Pubmed]
  13. The role of recombinant human erythropoietin in the treatment of thalassemia. Rachmilewitz, E.A., Aker, M. Ann. N. Y. Acad. Sci. (1998) [Pubmed]
  14. Melanin-concentrating hormone receptor 1 deficiency increases insulin sensitivity in obese leptin-deficient mice without affecting body weight. Bjursell, M., Gerdin, A.K., Ploj, K., Svensson, D., Svensson, L., Oscarsson, J., Snaith, M., Törnell, J., Bohlooly-Y, M. Diabetes (2006) [Pubmed]
  15. Leptin resistance and enhancement of feeding facilitation by melanin-concentrating hormone in mice lacking bombesin receptor subtype-3. Maekawa, F., Quah, H.M., Tanaka, K., Ohki-Hamazaki, H. Diabetes (2004) [Pubmed]
  16. Antiobesity effect of a melanin-concentrating hormone 1 receptor antagonist in diet-induced obese mice. Mashiko, S., Ishihara, A., Gomori, A., Moriya, R., Ito, M., Iwaasa, H., Matsuda, M., Feng, Y., Shen, Z., Marsh, D.J., Bednarek, M.A., MacNeil, D.J., Kanatani, A. Endocrinology (2005) [Pubmed]
  17. Characterization of expression of hypothalamic appetite-regulating peptides in obese hyperleptinemic brown adipose tissue-deficient (uncoupling protein-promoter-driven diphtheria toxin A) mice. Tritos, N.A., Elmquist, J.K., Mastaitis, J.W., Flier, J.S., Maratos-Flier, E. Endocrinology (1998) [Pubmed]
  18. Melanin-concentrating hormone activates signaling pathways in 3T3-L1 adipocytes. Bradley, R.L., Mansfield, J.P., Maratos-Flier, E., Cheatham, B. Am. J. Physiol. Endocrinol. Metab. (2002) [Pubmed]
  19. Different structural requirements for melanin-concentrating hormone (MCH) interacting with rat MCH-R1 (SLC-1) and mouse B16 cell MCH-R. Schlumberger, S.E., Saito, Y., Giller, T., Hintermann, E., Tanner, H., Jäggin, V., Zumsteg, U., Civelli, O., Eberle, A.N. J. Recept. Signal Transduct. Res. (2003) [Pubmed]
  20. Discovery of bicycloalkyl urea melanin concentrating hormone receptor antagonists: orally efficacious antiobesity therapeutics. McBriar, M.D., Guzik, H., Xu, R., Paruchova, J., Li, S., Palani, A., Clader, J.W., Greenlee, W.J., Hawes, B.E., Kowalski, T.J., O'Neill, K., Spar, B., Weig, B. J. Med. Chem. (2005) [Pubmed]
  21. MCH-/- mice are resistant to aging-associated increases in body weight and insulin resistance. Jeon, J.Y., Bradley, R.L., Kokkotou, E.G., Marino, F.E., Wang, X., Pissios, P., Maratos-Flier, E. Diabetes (2006) [Pubmed]
  22. Melanin-concentrating hormone-1 receptor modulates neuroendocrine, behavioral, and corticolimbic neurochemical stress responses in mice. Smith, D.G., Davis, R.J., Rorick-Kehn, L., Morin, M., Witkin, J.M., McKinzie, D.L., Nomikos, G.G., Gehlert, D.R. Neuropsychopharmacology (2006) [Pubmed]
  23. Agouti-related protein-like immunoreactivity: characterization of release from hypothalamic tissue and presence in serum. Li, J.Y., Finniss, S., Yang, Y.K., Zeng, Q., Qu, S.Y., Barsh, G., Dickinson, C., Gantz, I. Endocrinology (2000) [Pubmed]
  24. Characterization of melanin concentrating hormone and preproorexin expression in the murine hypothalamus. Tritos, N.A., Mastaitis, J.W., Kokkotou, E., Maratos-Flier, E. Brain Res. (2001) [Pubmed]
  25. Characterization of MCH-mediated obesity in mice. Ito, M., Gomori, A., Ishihara, A., Oda, Z., Mashiko, S., Matsushita, H., Yumoto, M., Ito, M., Sano, H., Tokita, S., Moriya, M., Iwaasa, H., Kanatani, A. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  26. Neuropeptides, including neuropeptide Y and melanocortins, mediate lipolysis in murine adipocytes. Bradley, R.L., Mansfield, J.P., Maratos-Flier, E. Obes. Res. (2005) [Pubmed]
  27. Melanin concentrating hormone is a novel regulator of islet function and growth. Pissios, P., Ozcan, U., Kokkotou, E., Okada, T., Liew, C.W., Liu, S., Peters, J.N., Dahlgren, G., Karamchandani, J., Kudva, Y.C., Kurpad, A.J., Kennedy, R.T., Maratos-Flier, E., Kulkarni, R.N. Diabetes (2007) [Pubmed]
  28. Hypocretin/orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: relationship to the neuropeptide Y and agouti gene-related protein systems. Broberger, C., De Lecea, L., Sutcliffe, J.G., Hökfelt, T. J. Comp. Neurol. (1998) [Pubmed]
  29. Effects of leptin on melanin-concentrating hormone expression in the brain of lean and obese Lep(ob)/Lep(ob) mice. Huang, Q., Viale, A., Picard, F., Nahon, J., Richard, D. Neuroendocrinology (1999) [Pubmed]
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