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Gene Review

Mc3r  -  melanocortin 3 receptor

Mus musculus

Synonyms: MC3-R, Melanocortin receptor 3
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Disease relevance of Mc3r

  • In conclusion, agonism at MC3-R expressed on peritoneal M phi leads to inhibition of experimental nonimmune peritonitis in both wild-type and recessive yellow (e/e) mice [1].
  • A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse [2].
  • (Feed efficiency is the ratio of weight gain to food intake.) Consistent with increased fat mass, Mc3r(-/-) mice are hyperleptinaemic and male Mc3r(-/-) mice develop mild hyperinsulinaemia [3].
  • MC-3 receptor and the inflammatory mechanisms activated in acute myocardial infarct [4].
  • Here we show that among 355 overweight and nonoverweight children, 8.2% were double homozygous for a pair of missense MC3R sequence variants (Thr6Lys and Val81Ile) [5].

Psychiatry related information on Mc3r


High impact information on Mc3r


Biological context of Mc3r

  • To assess the role of the MC3-R in energy homeostasis, the majority of the mc3r coding sequence was deleted from the mouse genome [2].
  • Studies using nonselective agonists and antagonists of melanocortin-3 receptor (MC3R) and MC4R point to the importance of the CNS melanocortin system in the control of food intake [9].
  • We report here the isolation of the chicken gene for MC3-R, CMC3, displaying different tissue distribution from mammalian counterparts [10].
  • Little is known about how Mc3r or Mc4r genotype, diet, and obesity affect insulin sensitivity [11].
  • In conclusion, these data support the development of the selective MC3R agonist [d-Trp(8)]-gamma-MSH for the treatment of inflammatory pathologies, based on a dual mechanism of cytokine/chemokine inhibition and induction of the anti-inflammatory protein HO-1 [12].

Anatomical context of Mc3r


Associations of Mc3r with chemical compounds

  • CONCLUSIONS: The present results suggest that MC4R, and not MC3R, modulates MCR agonist-induced reduction of ethanol consumption and that ethanol intake is increased by the antagonistic actions of AgRP-(83-132) [15].
  • These studies provide further experimental evidence that the His(6) position can determine MC4R versus MC3R agonist selectivity and that chemically nonreactive side chains may be substituted for the imidazole ring (generally needs to be side chain protected in synthetic schemes) in the design of MC4R-selective, small-molecule, non-peptide agonists [16].
  • Effect of estrogen on melanocortin-3 receptor mRNA expression in mouse pituitary glands in vivo and in vitro [17].

Other interactions of Mc3r


Analytical, diagnostic and therapeutic context of Mc3r

  • Two melanocortin receptors (MC1 and MC3R) have been identified as main transducers of the anti-inflammatory effects of natural and synthetic melanocortins [12].
  • Northern blot analysis revealed a 2.7-kb transcript for MC3-R mRNA in the anterior and neurointermediate lobes of pituitary glands of adult male and female mice [21].
  • In conclusion, this study has highlighted a previously unrecognized protective role for MC3-R activation on acute and delayed heart reperfusion injury [4].
  • Western blotting also showed the presence of MC3-R protein on murine peritoneal Mø. Furthermore, agonism at the MC3-R evoked accumulation of cAMP within the Mø, which was inhibited by SHU9119 [22].
  • Ovariectomy decreased MC3-R mRNA expression in the female anterior lobes, and estradiol-17beta (E(2)) treatment increased MC3-R mRNA levels in ovariectomized mouse anterior lobes and cultured anterior pituitary cells [17].


  1. Redundancy of a functional melanocortin 1 receptor in the anti-inflammatory actions of melanocortin peptides: studies in the recessive yellow (e/e) mouse suggest an important role for melanocortin 3 receptor. Getting, S.J., Christian, H.C., Lam, C.W., Gavins, F.N., Flower, R.J., Schiöth, H.B., Perretti, M. J. Immunol. (2003) [Pubmed]
  2. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Butler, A.A., Kesterson, R.A., Khong, K., Cullen, M.J., Pelleymounter, M.A., Dekoning, J., Baetscher, M., Cone, R.D. Endocrinology (2000) [Pubmed]
  3. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Chen, A.S., Marsh, D.J., Trumbauer, M.E., Frazier, E.G., Guan, X.M., Yu, H., Rosenblum, C.I., Vongs, A., Feng, Y., Cao, L., Metzger, J.M., Strack, A.M., Camacho, R.E., Mellin, T.N., Nunes, C.N., Min, W., Fisher, J., Gopal-Truter, S., MacIntyre, D.E., Chen, H.Y., Van der Ploeg, L.H. Nat. Genet. (2000) [Pubmed]
  4. MC-3 receptor and the inflammatory mechanisms activated in acute myocardial infarct. Getting, S.J., Di Filippo, C., Christian, H.C., Lam, C.W., Rossi, F., D'Amico, M., Perretti, M. J. Leukoc. Biol. (2004) [Pubmed]
  5. Co-occurrence of two partially inactivating polymorphisms of MC3R is associated with pediatric-onset obesity. Feng, N., Young, S.F., Aguilera, G., Puricelli, E., Adler-Wailes, D.C., Sebring, N.G., Yanovski, J.A. Diabetes (2005) [Pubmed]
  6. Behavioral, physiological, and molecular differences in response to dietary restriction in three inbred mouse strains. Gelegen, C., Collier, D.A., Campbell, I.C., Oppelaar, H., Kas, M.J. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  7. Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat. Butler, A.A., Marks, D.L., Fan, W., Kuhn, C.M., Bartolome, M., Cone, R.D. Nat. Neurosci. (2001) [Pubmed]
  8. A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors. Ste Marie, L., Miura, G.I., Marsh, D.J., Yagaloff, K., Palmiter, R.D. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  9. A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. Benoit, S.C., Schwartz, M.W., Lachey, J.L., Hagan, M.M., Rushing, P.A., Blake, K.A., Yagaloff, K.A., Kurylko, G., Franco, L., Danhoo, W., Seeley, R.J. J. Neurosci. (2000) [Pubmed]
  10. A possible involvement of melanocortin 3 receptor in the regulation of adrenal gland function in the chicken. Takeuchi, S., Takahashi, S. Biochim. Biophys. Acta (1999) [Pubmed]
  11. Diet-genotype interactions in the development of the obese, insulin-resistant phenotype of C57BL/6J mice lacking melanocortin-3 or -4 receptors. Sutton, G.M., Trevaskis, J.L., Hulver, M.W., McMillan, R.P., Markward, N.J., Babin, M.J., Meyer, E.A., Butler, A.A. Endocrinology (2006) [Pubmed]
  12. [D-Trp8]-{gamma}-Melanocyte-Stimulating Hormone Exhibits Anti-Inflammatory Efficacy in Mice Bearing a Nonfunctional MC1R (Recessive Yellow e/e Mouse). Getting, S.J., Lam, C.W., Leoni, G., Gavins, F.N., Grieco, P., Perretti, M. Mol. Pharmacol. (2006) [Pubmed]
  13. Targeted deletion of melanocortin receptor subtypes 3 and 4, but not CART, alters nutrient partitioning and compromises behavioral and metabolic responses to leptin. Zhang, Y., Kilroy, G.E., Henagan, T.M., Prpic-Uhing, V., Richards, W.G., Bannon, A.W., Mynatt, R.L., Gettys, T.W. FASEB J. (2005) [Pubmed]
  14. Cat odour exposure decreases exploratory activity and alters neuropeptide gene expression in CCK(2) receptor deficient mice, but not in their wild-type littermates. Areda, T., Raud, S., Philips, M.A., Innos, J., Matsui, T., Kõks, S., Vasar, E., Karis, A., Asser, T. Behav. Brain Res. (2006) [Pubmed]
  15. Effects of melanocortin receptor activation and blockade on ethanol intake: a possible role for the melanocortin-4 receptor. Navarro, M., Cubero, I., Chen, A.S., Chen, H.Y., Knapp, D.J., Breese, G.R., Marsh, D.J., Thiele, T.E. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
  16. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH(2) at the mouse melanocortin receptors. 1. Modifications at the His position. Holder, J.R., Bauzo, R.M., Xiang, Z., Haskell-Luevano, C. J. Med. Chem. (2002) [Pubmed]
  17. Effect of estrogen on melanocortin-3 receptor mRNA expression in mouse pituitary glands in vivo and in vitro. Matsumura, R., Takeuchi, S., Takahashi, S. Neuroendocrinology (2004) [Pubmed]
  18. Elongation studies of the human agouti-related protein (AGRP) core decapeptide (Yc[CRFFNAFC]Y) results in antagonism at the mouse melanocortin-3 receptor. Joseph, C.G., Bauzo, R.M., Xiang, Z., Shaw, A.M., Millard, W.J., Haskell-Luevano, C. Peptides (2003) [Pubmed]
  19. Melanocortin receptors mediate alpha-MSH-induced stimulation of neurite outgrowth in neuro 2A cells. Adan, R.A., van der Kraan, M., Doornbos, R.P., Bär, P.R., Burbach, J.P., Gispen, W.H. Brain Res. Mol. Brain Res. (1996) [Pubmed]
  20. The genes for endothelin 3, vitamin D 24-hydroxylase, and melanocortin 3 receptor map to distal mouse chromosome 2, in the region of conserved synteny with human chromosome 20. Malas, S., Peters, J., Abbott, C. Mamm. Genome (1994) [Pubmed]
  21. Alpha-melanocyte-stimulating hormone stimulates prolactin secretion through melanocortin-3 receptors expressed in mammotropes in the mouse pituitary. Matsumura, R., Takagi, C., Kakeya, T., Okuda, K., Takeuchi, S., Takahashi, S. Neuroendocrinology (2003) [Pubmed]
  22. Natural and synthetic agonists of the melanocortin receptor type 3 possess anti-inflammatory properties. Getting, S.J., Allcock, G.H., Flower, R., Perretti, M. J. Leukoc. Biol. (2001) [Pubmed]
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