Abstract
The cloning of the genes for the melanocortin receptors (Chapter 7) and of the agouti proteins (Chapter 14), as well as the identification of melanocortin receptor subtype specific agonists and antagonists (Chapter 8) have produced some powerful new tools for the study of the melanocortin physiology. These advances, as well as advances in understanding the physiological roles of the melanocortins, appear to be responsible for a dramatic ten-fold increase in publications on the topic over the last five years (Fig. 1), at least as searched under the keyword “melanocortin.” The finding of a role for the MC4-R in energy homeostasis has, for the first time, attracted a very significant effort in the area from the pharmaceutical industry as well. One industry-watcher has told me that there are now about 40 biotechnology and pharmaceutical companies doing some sort of research on the MC4-R for the treatment of obesity.
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References
Searle, A. G. (1968) Comparative Genetics of Coat Colors in Mammals Logos Press, London.
Klungland, H., Vage, D. I., Gomez-Raya, L., Adelsteinsson, S., and Lien, S. (1995) The role of melanocyte-stimulating hormone (MSH) receptor in bovine coat color determination. Mamm. Genome 6, 636–639.
Robbins, L. S., Nadeau, J. H., Johnson, K. R., Kelly, M. A., Roselli-Rehfuss, L., Baack, E., Mountjoy, K. G., and Cone, R. D. (1993) Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function. Cell 72, 827–834.
Vage, D., Klungland, H., Lu, D., and Cone, R. (1999) Molecular and pharmacological characterization of dominantblack coat color in sheep. Mamm. Genome 10, 39–43.
Vage, D. I., Lu, D., Klungland, H., Lien, S., Adalsteinsson, S., and Cone, R.D. (1997) A non-epistatic interaction of agouti and extension in the fox, Vulpes vulpes. Nat. Genet. 15, 311–315.
Lyon, M. F. (1961) Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 190, 372–373.
Kapas, S., Cammas, F. M., Hinson, J. P., and Clark, A. J. L. (1996) Agonist and receptor binding properties of adrenocorticotropin peptides using the cloned mouse adrenocorticotropin receptor expressed in a stably transfected HeLa cell line. Endocrinology 137, 3291–3294.
Ni, X.-P., Kesterson, R. A., Sharma, S. D., Hruby, V. J., Cone, R. D., Wiedemann, E., and Humphreys, M. H. (1998) Prevention of reflex natriuresis after acute unilateral nephrectomy by melanocortin receptor antagonists. Am. J. Physiol. 274, R931 - R938.
Gantz, I., Konda, Y., Tashiro, T., Shimoto, Y., Miwa, H., Munzert, G., Watson, S. J., Del Valle, J., and Yamada, T. (1993) Molecular cloning of a novel melanocortin receptor. J. Biol. Chem. 268, 8246–8250.
Roselli-Rehfuss, L., Mountjoy, K. G., Robbins, L. S., Mortrud, M. T., Low, M. J., Tatro, J. B., Entwistle, M. L., Simerly, R., and Cone, R. D. (1993) Identification of a receptor for y-MSH and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc. Natl. Acad. Sci. U. S. A. 90, 8856–8860.
Mizuno, T. M. and Mobbs, C. V. (1999) Hypothalamic agouti-related messenger ribonucleic acid is inhibited by leptin and stimulated by fasting. Endocrinology 140, 814–817.
Ollmann, M. M., Wilson, B. D., Yang, Y.-K., Kerns, J. A., Chen, Y., Gantz, I., and Barsh, G. S. (1997) Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 278, 135–137.
Shutter, J. R., Graham, M., Kinsey, A. C., Scully, S., Luthy, R., and Stark, K. L. (1997) Hypothalamic expression of ART, a novel gene related to agouti, is upregulated in obese and diabetic mutant mice. Genes Dev. 11, 593–602.
Fong, T. M., Mao, C., MacNeil, C., Kalyani, R., Smith, T., Weinberg, D., Tota, M. R., and Van der Ploeg, L. H. (1997) ART (protein product of agouti-related transcript) as an antagonist of MC-3 and MC-4 receptors. Biochem. Biophys. Res. Commun. 237, 629–631.
Graham, M., Shuttre, J. R., Sarmiento, U., Sarosi, I., and Stark, K. L. (1997) Overexpression of Agrt leads to obesity in transgenic mice. Nat. Genet. 17, 273–274.
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., Smith, F. J., Campfield, L. A., Burn, P., and Lee, F. (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131–141.
Marsh, D. J., Hollopeter, G., Huszar, D., Laufer, R., Yagaloff, K. A., Fisher, S. L., Burn, P., and Palmiter, R. D. (1999) Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Nat. Genet. 21, 119–122.
Vaisse, C., Clement, K., Guy-Grand, B., and Froguel, P. (1998) A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat. Genet. 20, 113–114.
Yeo, G. S. H., Farooqi, I. S., Aminian, S., Halsall, D. J., Stanhope, R. G., and O’Rahilly, S. (1998) A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat. Genet. 20, 111–112.
Li, S.-J., Varga, K., Archer, P., Hruby, V. J., Sharma, S. D., Kesterson, R. A., Cone, R. D., and Kunos, G. (1996) Melanocortin antagonists define two distinct pathways of cardiovascular control by a-and y-melanopcyte-stimulating hormones. J. Neurosci. 16, 5182–5188.
Huang, Q.-H., Entwistle, M. L., Alvaro, J. D., Duman, R. S., Hruby, V. J., and Tatro, J. B. (1997) Antipyretic role of endogenous melanocortins mediated by central melanocortin receptors during endotoxin-induced fever. J. Neurosci. 17, 3343–3351.
Von Frijtag, J. C., Croiset, G., Gispen, W. H., Adan, R. A., and Wiegant, V. M. (1998) The role of central melanocortin receptors in the activation of the hypothalamus-pituitary-adrenal-axis and the induction of excessive grooming. Br. J. Pharmacol. 123, 1503–1508.
Chen, W., Kelly, M. A., Opitz-Araya, X., Thomas, R. E., Low, M. J., and Cone, R. D. (1997) Exocrine gland dysfunction in MC5-R deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell 91, 789–798.
van der Kraan, M., Adan, R. A. H., Entwistle, M. L., Gispen, W. H., Burbach, J. P. H., and Tatro, J. B. (1998) Expression of melanocortin-5 receptor in secretory epithelia supports a functional role in exocrine and endocrine glands. Endocrinology 139, 2348–2355.
Fathi, Z., Iben, L. G., and Parker, E. M. (1995) Cloning, expression, and tissue distribution of a fifth melanocortin receptor subtype. Neurochem. Res. 20, 107–113.
Labbe, O., Desarnaud, F., Eggerickx, D., Vassart, G., and Parmentier, M. (1994) Molecular cloning of a mouse melanocortin 5 receptor gene widely expressed in peripheral tissues. Biochemistry 33, 4543–4549.
Kraan, v. d., Tatro, J. B., Entwistle, M. L., Brakkee, J. H., Burbach, J. P. H., Adan, R. A. H., and Gispen, W. H. (1999) Expression of melanocortin receptors and proopiomelanocortin in the rat spinal cord in relation to the neurotrophic effects of melanocortins. Mol. Brain Res. 63, 276–286.
Lane, P. W. (1960) New mouse mutants. Mouse News Lett. 22, 35.
Lane, P. W. and Green, M. C. (1960) Mahogany, a recessive color mutation in linkage group V of the mouse. J. Hered. 51, 228–230.
Mather, K. and North, S. B. (1940) Umbrous: a case of dominance modification in mice. J. Genet. 40, 229–241.
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Cone, R.D. (2000). Future Vistas. In: Cone, R.D. (eds) The Melanocortin Receptors. The Receptors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-031-5_19
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DOI: https://doi.org/10.1007/978-1-59259-031-5_19
Publisher Name: Humana Press, Totowa, NJ
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