Increased alpha-melanocyte-stimulating hormone (alpha-MSH) levels and melanocortin receptors expression associated with pigmentation in an NC/Nga mouse model of atopic dermatitis.
ABSTRACT Patients with a specific subtype of atopic dermatitis (AD) display particular patterns of pigmentation, such as ripple pattern pigmentation on the neck, pigmented macules on the lip and diffuse pigmentation. However, the mechanism underlying these patterns has not been determined. The purpose of our research is to investigate the factors influencing this type of pigmentation in AD. We observed that AD model mice (NC/Nga mice) displayed an increase in the number of 3, 4-dihydroxyphenylalanine (Dopa)-positive melanocytes in the epidermis and intestine (jejunum and colon) while in the inflammatory state. The plasma levels of alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocoticotropin (ACTH) also increased in NC/Nga mice with dermatitis. Furthermore, the expression of melanocortin receptor 5 and melanocortin receptor 1 (MC1R) increased in the skin, and melanocortin receptor 3 (MC3R) expression increased in the intestine. However, the changes in the Dopa-positive cells of conventional NC/Nga mice were not induced by treatment with either agouti (an MC1R antagonist) or agouti-related protein (an MC3R antagonist). These results indicate that the pigmentation of AD is related to increased levels of alpha-MSH, MC1R (in the skin) and MC3R (in the intestines).
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ABSTRACT: The melanocortins are a family of bioactive peptides derived from proopiomelanocortin, and share significant structural similarity. Those peptides are best known for their stimulatory effects on pigmentation and steroidogenesis. Melanocortins are synthesized in various sites in the central nervous system and in peripheral tissues, and participate in regulating multiple physiological functions. Research during the past decade has provided evidence that melanocortins elicit their diverse biological effects by binding to a distinct family of G protein-coupled receptors with seven transmembrane domains. To date, five melanocortin receptor genes have been cloned and characterized. Those receptors differ in their tissue distribution and in their ability to recognize the various melanocortins and the physiological antagonists, agouti signaling protein and agouti-related protein. These advances have opened new horizons for exploring the significance of melanocortins, their antagonists, and their receptors in a variety of important physiological functions.Cellular and Molecular Life Sciences CMLS 04/2001; 58(3):434-41. · 5.62 Impact Factor
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ABSTRACT: Psychological stress is known to aggravate inflammatory skin diseases such as atopic dermatitis, psoriasis and contact sensitivity by altering the cellular constituents of the immune system. The skin appendages function dually as prominent targets and sources of the peripheral corticotropin-releasing hormone-proopiomelanocortin (CRH-POMC) axis. In this study, we examined the expression level of CRH-POMC axis constituents in psoriasis, a well-known stress-related inflammatory skin disease. The 15 psoriasis patients and six normal controls were retrospectively selected after extensive review of their clinical records and skin biopsy specimens. We immunohistochemically analysed the expressivity of CRH, adrenocorticotrophic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in various types of psoriatic lesions and control skin. A significant increase of CRH expression was observed in psoriatic lesions, which involved the entire epidermis (upper layer in particular), hair follicles and sweat glands compared with controls. Expression of ACTH and alpha-MSH was clearly stimulated in a subset of psoriasis patients compared with controls, but on the whole, lacked statistical significance. The immunoreactivity of CRH, ACTH and alpha-MSH in psoriasis was not dependent on its clinical subtype, duration or number of previous treatments. Compared with the definite increase of CRH expression in psoriasis, the expression of the POMC peptides was heterogenous with no overall significance. From the findings, we suggest that CRH, a key stress hormone, may play an important role in the pathomechanism of psoriasis.Experimental Dermatology 03/2007; 16(2):104-9. · 3.58 Impact Factor
Article: Atopic dermatitis.The Lancet 07/1998; 351(9117):1715-21. · 39.06 Impact Factor