Review Article

Melanocortin Receptors: Emerging Targets for the Treatment of Pigmentation, Inflammation, Stress, Weight Disorders and Sexual Dysfunction

Author(s): Miteshkumar Rajaram Maurya*, Renuka Munshi and Sachin Zambare

Volume 24, Issue 2, 2023

Published on: 25 November, 2022

Page: [151 - 156] Pages: 6

DOI: 10.2174/1389450124666221108143006

Price: $65

Abstract

Melanocortins are tiny protein molecules formed by the post-translational cleavage of proopiomelanocortin. These are bioactive peptides that are responsible for human and lower animal pigmentation patterns, energy homeostasis, and sexual function modulation. These peptides regulate numerous physiological functions by being generated in the central nervous system and peripheral tissues. Melanocortins elicit their varied biological effects by binding to a separate family of G protein, two primary proteolytic enzymes, proconvertases 1 and 2, according to recent research. These breakthroughs have opened up new avenues for research into the role of melanocortins, antagonists, and receptors in a number of physiological activities.

Keywords: Melanocortin receptors, agouti related peptide, proopiomelanocortin, melanotans, pigmentation treatment, melanin.

Graphical Abstract
[1]
Takahashi A, Mizusawa K. Posttranslational modifications of proopiomelanocortin in vertebrates and their biological significance. Front Endocrinol 2013; 4: 143.
[http://dx.doi.org/10.3389/fendo.2013.00143] [PMID: 24146662]
[2]
Vazquez-Martinez R, Castaño JP, Tonon MC, Vaudry H, Gracia-Navarro F, Malagon MM. Melanotrope secretory cycle is regulated by physiological inputs via the hypothalamus. Am J Physiol Endocrinol Metab 2003; 285(5): E1039-46.
[http://dx.doi.org/10.1152/ajpendo.00238.2003] [PMID: 12876074]
[3]
a) Switonski M, Mankowska M, Salamon S. Family of melanocortin receptor (MCR) genes in mammals-mutations, polymorphisms and phenotypic effects. J Appl Genet 2013; 54(4): 461-72.;
b) Kobayashi Y, Mizusawa K, Saito Y, Takahashi A. Melanocortin systems on pigment dispersion in fish chromatophores. Front Endocrinol 2012; 3: 9.
[4]
Nilsson Sköld H, Aspengren S, Wallin M. Rapid color change in fish and amphibians - function, regulation, and emerging applications. Pigment Cell Melanoma Res 2013; 26(1): 29-38.
[http://dx.doi.org/10.1111/pcmr.12040] [PMID: 23082932]
[5]
Krude H, Grüters A. Implications of proopiomelanocortin (POMC) mutations in humans: the POMC deficiency syndrome. Trends Endocrinol Metab 2000; 11(1): 15-22.
[http://dx.doi.org/10.1016/S1043-2760(99)00213-1] [PMID: 10652501]
[6]
Böhm M, Grässel S. Role of proopiomelanocortin-derived peptides and their receptors in the osteoarticular system: from basic to translational research. Endocr Rev 2012; 33(4): 623-51.
[http://dx.doi.org/10.1210/er.2011-1016] [PMID: 22736674]
[7]
Millington GWM. The role of proopiomelanocortin (POMC) neurones in feeding behaviour. Nutr Metab 2007; 4(1): 18.
[http://dx.doi.org/10.1186/1743-7075-4-18] [PMID: 17764572]
[8]
Lin JY, Fisher DE. Melanocyte biology and skin pigmentation. Nature 2007; 445(7130): 843-50.
[http://dx.doi.org/10.1038/nature05660] [PMID: 17314970]
[9]
Videira IFS, Moura DFL, Magina S. Mechanisms regulating melanogenesis. An Bras Dermatol 2013; 88(1): 76-83.
[http://dx.doi.org/10.1590/S0365-05962013000100009] [PMID: 23539007]
[10]
Healy E. Melanocortin 1 receptor variants, pigmentation, and skin cancer susceptibility. Photodermatol Photoimmunol Photomed 2004; 20(6): 283-8.
[http://dx.doi.org/10.1111/j.1600-0781.2004.00132.x] [PMID: 15533235]
[11]
Sulem P, Gudbjartsson DF, Stacey SN, et al. Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat Genet 2007; 39(12): 1443-52.
[http://dx.doi.org/10.1038/ng.2007.13] [PMID: 17952075]
[12]
Cal L, Suarez-Bregua P, Cerdá-Reverter JM, Braasch I, Rotllant J. Fish pigmentation and the melanocortin system. Comp Biochem Physiol A Mol Integr Physiol 2017; 211: 26-33.
[http://dx.doi.org/10.1016/j.cbpa.2017.06.001] [PMID: 28599948]
[13]
a) Wolf Horrell EM, Boulanger MC, D’Orazio JA. Melanocortin 1 receptor: Structure, function, and regulation. Front Genet 2016; 7: 95.
[PMID: 22051769];
b) Mahiques-Santos L. Melanotan. Actas Dermosifiliogr 2012; 103(4): 257-9.
[14]
Evans-Brown M, Dawson RT, Chandler M, McVeigh J. Use of melanotan I and II in the general population. BMJ 2009; 338(2): b566.
[http://dx.doi.org/10.1136/bmj.b566] [PMID: 19224885]
[15]
Ugwu SO, Blanchard J, Dorr RT, et al. Skin pigmentation and pharmacokinetics of melanotan-I in humans. Biopharm Drug Dispos 1997; 18(3): 259-69.
[http://dx.doi.org/10.1002/(SICI)1099-081X(199704)18:3<259:AID-BDD20>3.0.CO;2-X] [PMID: 9113347]
[16]
Mallory CW, Lopategui DM, Cordon BH. Melanotan tanning injection: A rare cause of priapism. Sex Med 2021; 9(1)100298
[http://dx.doi.org/10.1016/j.esxm.2020.100298] [PMID: 33460908]
[17]
Monge-Roffarello B, Labbe SM, Lenglos C, et al. The medial preoptic nucleus as a site of the thermogenic and metabolic actions of melanotan II in male rats. Am J Physiol Regul Integr Comp Physiol 2014; 307(2): R158-66.
[http://dx.doi.org/10.1152/ajpregu.00059.2014] [PMID: 24808495]
[18]
Vergoni AV, Bertolini A, Wikberg JES, Schiöth HB. Selective melanocortin MC4 receptor blockage reduces immobilization stress-induced anorexia in rats. Eur J Pharmacol 1999; 369(1): 11-5.
[http://dx.doi.org/10.1016/S0014-2999(99)00045-X] [PMID: 10204675]
[19]
Lim CT, Khoo B. Normal physiology of ACTH and GH release in the hypothalamus and anterior pituitary in man. In: Endotext. South Dartmouth (MA): MDText.com, Inc. 2000.
[20]
Patel HB, Montero-Melendez T, Greco KV, Perretti M. Melanocortin receptors as novel effectors of macrophage responses in inflammation. Front Immunol 2011; 2: 41.
[http://dx.doi.org/10.3389/fimmu.2011.00041] [PMID: 22566831]
[21]
Capsoni F, Ongari AM, Reali E, Catania A. Melanocortin peptides inhibit urate crystal-induced activation of phagocytic cells. Arthritis Res Ther 2009; 11(5): R151.
[http://dx.doi.org/10.1186/ar2827] [PMID: 19814819]
[22]
Schaible EV, Steinsträßer A, Jahn-Eimermacher A, et al. Single administration of tripeptide α-MSH(11-13) attenuates brain damage by reduced inflammation and apoptosis after experimental traumatic brain injury in mice. PLoS One 2013; 8(8)e71056
[http://dx.doi.org/10.1371/journal.pone.0071056] [PMID: 23940690]
[23]
Gantz I, Fong TM. The melanocortin system. Am J Physiol Endocrinol Metab 2003; 284(3): E468-74.
[http://dx.doi.org/10.1152/ajpendo.00434.2002] [PMID: 12556347]
[24]
Kang L, McIntyre KW, Gillooly KM, et al. A selective small molecule agonist of the melanocortin-1 receptor inhibits lipopolysaccharide-induced cytokine accumulation and leukocyte infiltration in mice. J Leukoc Biol 2006; 80(4): 897-904.
[http://dx.doi.org/10.1189/jlb.1204748] [PMID: 16888084]
[25]
Leoni G, Voisin M-B, Carlson K, Getting SJ, Nourshargh S, Perretti M. The melanocortin MC1 receptor agonist BMS-470539 inhibits leucocyte trafficking in the inflamed vasculature. Br J Pharmacol 2010; 160(1): 171-80.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00688.x] [PMID: 20331604]
[26]
Getting SJ, Christian HC, Flower RJ, Perretti M. Activation of melanocortin type 3 receptor as a molecular mechanism for adrenocorticotropic hormone efficacy in gouty arthritis. Arthritis Rheum 2002; 46(10): 2765-75.
[http://dx.doi.org/10.1002/art.10526] [PMID: 12384937]
[27]
Taketoshi O, Shigeyuki C. Melanocortin-4 receptor antagonists for the treatment of depression and anxiety disorders. Curr Top Med Chem 2007; 7(11): 1145-51.
[http://dx.doi.org/10.2174/156802607780906618] [PMID: 17584135]
[28]
Chaki S, Ogawa S, Toda Y, Funakoshi T, Okuyama S. Involvement of the melanocortin MC4 receptor in stress-related behavior in rodents. Eur J Pharmacol 2003; 474(1): 95-101.
[http://dx.doi.org/10.1016/S0014-2999(03)02033-8] [PMID: 12909200]
[29]
MacNeil DJ, Howard AD, Guan X, et al. The role of melanocortins in body weight regulation: Opportunities for the treatment of obesity. Eur J Pharmacol 2002; 450(1): 93-109.
[http://dx.doi.org/10.1016/S0014-2999(02)01989-1] [PMID: 12176114]
[30]
Kühnen P, Krude H, Biebermann H. Melanocortin-4 receptor signalling: Importance for weight regulation and obesity treatment. Trends Mol Med 2019; 25(2): 136-48.
[http://dx.doi.org/10.1016/j.molmed.2018.12.002] [PMID: 30642682]
[31]
Baldini G, Phelan KD. The melanocortin pathway and control of appetite-progress and therapeutic implications. J Endocrinol 2019; 241(1): R1-R33.
[http://dx.doi.org/10.1530/JOE-18-0596] [PMID: 30812013]
[32]
Ayers KL, Glicksberg BS, Garfield AS, et al. Melanocortin 4 receptor pathway dysfunction in obesity: Patient stratification aimed at MC4R agonist treatment. J Clin Endocrinol Metab 2018; 103(7): 2601-12.
[http://dx.doi.org/10.1210/jc.2018-00258] [PMID: 29726959]
[33]
Crovesy L, Rosado EL. Interaction between genes involved in energy intake regulation and diet in obesity. Nutrition 2019; •••: 67-68110547.
[http://dx.doi.org/10.1016/j.nut.2019.06.027] [PMID: 31472367]
[34]
Krashes MJ, Lowell BB, Garfield AS. Melanocortin-4 receptor–regulated energy homeostasis. Nat Neurosci 2016; 19(2): 206-19.
[http://dx.doi.org/10.1038/nn.4202] [PMID: 26814590]
[35]
Mul JD, Spruijt BM, Brakkee JH, Adan RAH. Melanocortin MC4 receptor-mediated feeding and grooming in rodents. Eur J Pharmacol 2013; 719(1-3): 192-201.
[http://dx.doi.org/10.1016/j.ejphar.2013.04.060] [PMID: 23872405]
[36]
Ückert S, Bannowsky A, Albrecht K, Kuczyk MA. Melanocortin receptor agonists in the treatment of male and female sexual dysfunctions: Results from basic research and clinical studies. Expert Opin Investig Drugs 2014; 23(11): 1477-83.
[http://dx.doi.org/10.1517/13543784.2014.934805] [PMID: 25096243]
[37]
Kingsberg SA, Clayton AH, Portman D, et al. Bremelanotide for the treatment of hypoactive sexual desire disorder. Obstet Gynecol 2019; 134(5): 899-908.
[http://dx.doi.org/10.1097/AOG.0000000000003500] [PMID: 31599840]
[38]
Faulkner LD, Dowling AR, Stuart RC, Nillni EA, Hill JW. Reduced melanocortin production causes sexual dysfunction in male mice with POMC neuronal insulin and leptin insensitivity. Endocrinology 2015; 156(4): 1372-85.
[http://dx.doi.org/10.1210/en.2014-1788] [PMID: 25590244]
[39]
Carl S, Sharma SD, Earle DC, Spana C, Hallam TJ. Melanocortins in the treatment of male and female sexual dysfunction. Curr Top Med Chem 2007; 7(11): 1137-44.
[http://dx.doi.org/10.2174/156802607780906681] [PMID: 17584134]

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