melanocyte stimulating hormones


Summary: Peptides with the ability to stimulate pigmented cells MELANOCYTES in mammals and MELANOPHORES in lower vertebrates. By stimulating the synthesis and distribution of MELANIN in these pigmented cells, they increase coloration of skin and other tissue. MSHs, derived from pro-opiomelanocortin (POMC), are produced by MELANOTROPHS in the INTERMEDIATE LOBE OF PITUITARY; CORTICOTROPHS in the ANTERIOR LOBE OF PITUITARY, and the hypothalamic neurons in the ARCUATE NUCLEUS OF HYPOTHALAMUS.

Top Publications

  1. Yang J, Guo H, Padilla R, Berwick M, Miao Y. Replacement of the Lys linker with an Arg linker resulting in improved melanoma uptake and reduced renal uptake of Tc-99m-labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone hybrid peptide. Bioorg Med Chem. 2010;18:6695-700 pubmed publisher
  2. Szewczyk J, Laudeman C, Sammond D, Villeneuve M, Minick D, Grizzle M, et al. A concise synthesis of 1,4-dihydro-[1,4]diazepine-5,7-dione, a novel 7-TM receptor ligand core structure with melanocortin receptor agonist activity. Bioorg Med Chem. 2010;18:1822-33 pubmed publisher
    ..Compounds dosed by intracerebroventricular and oral routes reduced PYY-induced food intake and this effect was reversed by the cyclic peptide MC4R antagonist SHU9119. ..
  3. Starowicz K, Mousa S, Obara I, Chocyk A, Przewłocki R, Wedzony K, et al. Peripheral antinociceptive effects of MC4 receptor antagonists in a rat model of neuropathic pain - a biochemical and behavioral study. Pharmacol Rep. 2009;61:1086-95 pubmed
    ..Therefore, a block of the MC4 receptors results in the antagonism of neuropathic pain and such treatment could be beneficial therapeutically for individuals with chronic neuropathic pain. ..
  4. Okada Y. [Overview in 45 years of studies on peptide chemistry]. Yakugaku Zasshi. 2009;129:1141-54 pubmed
    ..Initially, in order to study the structure-activity relationships of active center of alpha- and beta-melanocyte stimulating hormones (H-His-Phe-Arg-Trp-Gly-OH), we employed D-amino acids...
  5. Toda C, Shiuchi T, Lee S, Yamato Esaki M, Fujino Y, Suzuki A, et al. Distinct effects of leptin and a melanocortin receptor agonist injected into medial hypothalamic nuclei on glucose uptake in peripheral tissues. Diabetes. 2009;58:2757-65 pubmed publisher
    ..The leptin receptor in the ARC and MCR in the PVH regulate glucose uptake in BAT. Medial hypothalamic nuclei thus play distinct roles in leptin- and MT-II-induced glucose uptake in peripheral tissues. ..
  6. Blouet C, Jo Y, Li X, Schwartz G. Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit. J Neurosci. 2009;29:8302-11 pubmed publisher
    ..Our data identify a novel, specific hypothalamus-brainstem circuit that links amino acid availability and nutrient sensing to the control of food intake. ..
  7. Khaled M, Levy C, Fisher D. Control of melanocyte differentiation by a MITF-PDE4D3 homeostatic circuit. Genes Dev. 2010;24:2276-81 pubmed publisher
    ..This homeostatic pathway highlights a potent mechanism controlling melanocyte differentiation that may be amenable to pharmacologic manipulation for skin cancer prevention...
  8. Dubinion J, da Silva A, Hall J. Enhanced blood pressure and appetite responses to chronic central melanocortin-3/4 receptor blockade in dietary-induced obesity. J Hypertens. 2010;28:1466-70 pubmed publisher
    ..These observations suggest that a high-fat diet increases endogenous activity of the CNS MC3/4R and that an intact MC3/4 appears to play an important role in linking increased blood pressure with diet-induced obesity. ..
  9. Laroui H, Dalmasso G, Nguyen H, Yan Y, Sitaraman S, Merlin D. Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model. Gastroenterology. 2010;138:843-53.e1-2 pubmed publisher
    ..Administration of encapsulated drug-loaded NPs is a novel therapeutic approach for IBD. ..

More Information


  1. De Silva C, Vagner J, Lynch R, Gillies R, Hruby V. Optimization of time-resolved fluorescence assay for detection of europium-tetraazacyclododecyltetraacetic acid-labeled ligand-receptor interactions. Anal Biochem. 2010;398:15-23 pubmed publisher
    ..The modified assay provides superior results and is appropriate for high-throughput screening of ligand libraries...
  2. Cantorias M, Figueroa S, Quinn T, Lever J, Hoffman T, Watkinson L, et al. Development of high-specific-activity (68)Ga-labeled DOTA-rhenium-cyclized alpha-MSH peptide analog to target MC1 receptors overexpressed by melanoma tumors. Nucl Med Biol. 2009;36:505-13 pubmed publisher
  3. Qu H, Cai M, Mayorov A, Grieco P, Zingsheim M, Trivedi D, et al. Substitution of arginine with proline and proline derivatives in melanocyte-stimulating hormones leads to selectivity for human melanocortin 4 receptor. J Med Chem. 2009;52:3627-35 pubmed publisher
    ..These findings are important for a better understanding of the selectivity mechanism at the hMC3R/hMC4R and the development of therapeutic ligands selectively targeting the hMC4R. ..
  4. Davis I, Kim J, Ozsolak F, Widlund H, Rozenblatt Rosen O, Granter S, et al. Oncogenic MITF dysregulation in clear cell sarcoma: defining the MiT family of human cancers. Cancer Cell. 2006;9:473-84 pubmed
    ..Seemingly unrelated tumors thus employ distinct strategies to oncogenically dysregulate the MiT family, collectively broadening the definition of MiT-associated human cancers...
  5. Yosten G, Samson W. The melanocortins, not oxytocin, mediate the anorexigenic and antidipsogenic effects of neuronostatin. Peptides. 2010;31:1711-4 pubmed publisher
    ..Neuronostatin-induced anorexia was not reversed by pretreatment with the oxytocin receptor antagonist, OVT, suggesting that neuronostatin acts through a unique subset of POMC neurons that do not signal via central oxytocin receptors. ..
  6. Skibicka K, Grill H. Hindbrain leptin stimulation induces anorexia and hyperthermia mediated by hindbrain melanocortin receptors. Endocrinology. 2009;150:1705-11 pubmed publisher
  7. Zheng H, Patterson L, Rhodes C, Louis G, Skibicka K, Grill H, et al. A potential role for hypothalamomedullary POMC projections in leptin-induced suppression of food intake. Am J Physiol Regul Integr Comp Physiol. 2010;298:R720-8 pubmed publisher
    ..The results further support the existence of POMC projections from the hypothalamus to the NTS and suggest that these projections have a functional role in the control of food intake. ..
  8. Dores R. Adrenocorticotropic hormone, melanocyte-stimulating hormone, and the melanocortin receptors: revisiting the work of Robert Schwyzer: a thirty-year retrospective. Ann N Y Acad Sci. 2009;1163:93-100 pubmed publisher
    ..This mini review will evaluate how the predictions made in the 1977 review have held up and also propose a mechanism to explain the ligand selectivity properties of the melanocortin receptors. ..
  9. Murakami M, Matsuzaki F, Funaba M. Regulation of melanin synthesis by the TGF-beta family in B16 melanoma cells. Mol Biol Rep. 2009;36:1247-50 pubmed publisher
    ..The present study indicates that in addition to TGF-beta, activin negatively regulates melanogenesis in the absence of alpha-MSH, but that the activity in the presence of alpha-MSH was slightly different between TGF-beta and activin. ..
  10. Dietrich M, Antunes C, Geliang G, Liu Z, Borok E, Nie Y, et al. Agrp neurons mediate Sirt1's action on the melanocortin system and energy balance: roles for Sirt1 in neuronal firing and synaptic plasticity. J Neurosci. 2010;30:11815-25 pubmed publisher
    ..The present data indicate that Sirt1 has a central mode of action by acting on the NPY/Agrp neurons to affect body metabolism. ..
  11. Yosten G, Samson W. Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system. Am J Physiol Regul Integr Comp Physiol. 2009;297:R330-6 pubmed publisher
    ..Thus we have identified a novel action of nesfatin-1, in addition to its anorexigenic effects, to stimulate autonomic nervous system activity. ..
  12. Tanaka M, Suganami T, Sugita S, Shimoda Y, Kasahara M, Aoe S, et al. Role of central leptin signaling in renal macrophage infiltration. Endocr J. 2010;57:61-72 pubmed
  13. Kobayashi Y, Mizusawa K, Yamanome T, Chiba H, Takahashi A. Possible paracrine function of alpha-melanocyte-stimulating hormone and inhibition of its melanin-dispersing activity by N-terminal acetylation in the skin of the barfin flounder, Verasper moseri. Gen Comp Endocrinol. 2009;161:419-24 pubmed publisher
    ..A series of bioassays indicated that acetylation enhances MSH activity in xanthophores, but inhibits it in melanophores, suggesting that receptors for MSHs expressed in xanthophores and melanophores are different from each other...
  14. Vossmerbaeumer U, Ohnesorge S, Kuehl S, Haapalahti M, Kluter H, Jonas J, et al. Retinal pigment epithelial phenotype induced in human adipose tissue-derived mesenchymal stromal cells. Cytotherapy. 2009;11:177-88 pubmed publisher
    ..The gain of basic functional features of RPE cells was indicated by melanin synthesis. This alludes to a differentiation potential of MSC into the neuroectodermal lineage, yielding cells with phenotypic characteristics of RPE cells. ..
  15. Miller C, Murakami P, Ruczinski I, Ross R, Sinkus M, Sullivan B, et al. Two complex genotypes relevant to the kynurenine pathway and melanotropin function show association with schizophrenia and bipolar disorder. Schizophr Res. 2009;113:259-67 pubmed publisher
  16. Bariohay B, Roux J, Tardivel C, Trouslard J, Jean A, Lebrun B. Brain-derived neurotrophic factor/tropomyosin-related kinase receptor type B signaling is a downstream effector of the brainstem melanocortin system in food intake control. Endocrinology. 2009;150:2646-53 pubmed publisher
    ..Our results provide strong evidence for a role of BDNF as a downstream effector of melanocortinergic signaling pathway within the DVC. ..
  17. Eagleson G, van der Heijden R, Roubos E, Jenks B. A developmental analysis of periodic albinism in the amphibian Xenopus laevis. Gen Comp Endocrinol. 2010;168:302-6 pubmed publisher
  18. Verty A, Allen A, Oldfield B. The endogenous actions of hypothalamic peptides on brown adipose tissue thermogenesis in the rat. Endocrinology. 2010;151:4236-46 pubmed publisher
    ..These findings support a role for endogenous orexigenic and anorexigenic hypothalamic peptides acting in concert to create a thermogenic tone via BAT activity. ..
  19. Chen P, Wang D, Li M, Zhang Y, Quirion R, Hong Y. Modulation of sensory neuron-specific receptors in the development of morphine tolerance and its neurochemical mechanisms. J Neurosci Res. 2010;88:2952-63 pubmed publisher
  20. Sánchez E, Rubio V, Thompson D, Metz J, Flik G, Millhauser G, et al. Phosphodiesterase inhibitor-dependent inverse agonism of agouti-related protein on melanocortin 4 receptor in sea bass (Dicentrarchus labrax). Am J Physiol Regul Integr Comp Physiol. 2009;296:R1293-306 pubmed publisher
    ..This suggests that inverse agonism and competitive antagonism operate through different intracellular signaling pathways, a view that opens up new targets for the treatment of melanocortin-induced metabolic syndrome. ..
  21. Lennquist A, Mårtensson Lindblad L, Hedberg D, Kristiansson E, Förlin L. Colour and melanophore function in rainbow trout after long term exposure to the new antifoulant medetomidine. Chemosphere. 2010;80:1050-5 pubmed publisher
    ..The number of melanophores in the scales did not change significantly after long term exposure to medetomidine. These results suggest that the observed paleness may be reversible, even after chronic exposure. ..
  22. Cai M, Nyberg J, Hruby V. Melanotropins as drugs for the treatment of obesity and other feeding disorders: potential and problems. Curr Top Med Chem. 2009;9:554-63 pubmed
    ..Current progress in these areas with special emphasis on the MC3R will be discussed along with possible new directions that might be fruitful in these important aspects of contemporary biology and medicine. ..
  23. Wallingford N, Perroud B, Gao Q, Coppola A, Gyengesi E, Liu Z, et al. Prolylcarboxypeptidase regulates food intake by inactivating alpha-MSH in rodents. J Clin Invest. 2009;119:2291-303 pubmed publisher
    ..Our results suggest that PRCP is an important component of melanocortin signaling and weight maintenance via control of active alpha-MSH1-13 levels. ..
  24. da Silva A, do Carmo J, Freeman J, Tallam L, Hall J. A functional melanocortin system may be required for chronic CNS-mediated antidiabetic and cardiovascular actions of leptin. Diabetes. 2009;58:1749-56 pubmed publisher