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Foreward:alpha-melanocyte stimulating hormone and the melanocortin receptors.

There are very few topics in science that involve different biological systems and cross different scientific disciplines as research on alpha-melanocyte stimulating hormone (alpha-MSH) and its melanocortin receptors. Such research has involved the analysis and examination of neurological tissues, endocrine glands, immune cells, and tumor cells. The researchers have backgrounds in endocrinology, neurology, immunology, biochemistry, and medicine. This is represented by the manuscripts in this theme issue by the leading researchers in alpha-MSH and melanocortin receptors. The complexity of the melanocortin family of peptides is covered by Wilson demonstrating in various endogenous and synthetic melanocortin peptides a common amino acid sequence important in binding the melanocortin receptors. As Wilson focused on melanocortin regulation of feeding behavior and weight homeostasis, Wood's interests are in melanocortin regulation of melanogenesis. Wood uses X-ray crystal structures to model the melanocortin-1 receptor to show through structural fitting the affinity of melanocortin peptides and the implications of finding significantly different affinities by the melanocortins in the skin. Continuing with melanocytes, Rouzaud's microarray analysis finds alpha-MSH up-regulating melanocyte genes involved in a wide range of biological functions involving cell survival, transformation, transcription, keratin associated proteins, and interestingly genes for body weight control. This presentation once again shows the range of biological activities regulated by the melanocortins. Biros presents an interesting finding that some of the alpha-MSH regulation in immunity may not be limited to gene activation. In T cells, alpha -MSH induces a post-translational regulation of Interferon-? production through ubiquitination, not through down- regulation of gene expression. An understanding of the endogenous role of the melanocortins is emerging from knock-out mice. Karpac shows in pro-opiomelanocortin knock-out mice that besides suffering from obesity, pigment defects, and adrenal insufficiency they succumb to spontaneous pituitary adenomas. This expands the biological activity regulated by the melanocortins to cellular proliferation and regulation of transformation. In my own report we used melanocortin-5 receptor knock-out mice to demonstrate the possibility that each melanocortin receptor has a different role in the regulation of immunity and inflammation. Sanchez-Laorden demonstrates an abnormal processing and expression of the melanocortin- 1 receptor in natural human melanocortin-1 receptor variants. Colombo finds that alpha-MSH treatment changes the genotype and the phenotype of malignant mesothelial cells demonstrating the ability of alpha-MSH to influence the basic pathways of cellular proliferation in malignant cells. Such results support a physiological requirement for the melanocortins to influence a specific set of biological functions and an intolerance to express genetic variations in the melanocortin family of molecules. It is both amazing and humbling that a thirteen amino acid peptide (alpha-MSH) originally described for its melanogenic properties in amphibians may very well have a central role in the regulation of metabolism, malignancy, and immunity of mammals. However, the reports in this issue show that it is much more than alpha-MSH alone and that there is a fundamental importance of the melanocortin family of molecules to health and survival. Also, the reports are an example of the interconnections between different biological systems regulated by the melanocortins reflecting the challenge to match the increasing need for multi-disciplinary approaches to fully realize the promise of modern biomedical research.[1]

References

  1. Foreward:alpha-melanocyte stimulating hormone and the melanocortin receptors. Taylor, A. Cell. Mol. Biol. (Noisy-le-grand) (2006) [Pubmed]
 
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