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Proopiomelanocortin (POMC), the ACTH/melanocortin precursor, is secreted by human epidermal keratinocytes and melanocytes and stimulates melanogenesis

Lookup NU author(s): Professor Anthony Thody

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Abstract

Proopiomelanocortin (POMC) can be processed to ACTH and melanocortin peptides. However, processing is incomplete in some tissues, leading to POMC precursor release from cells. This study examined POMC processing in human skin and the effect of POMC on the melanocortin-1 receptor (MC-1R) and melanocyte regulation. POMC was secreted by both human epidermal keratinocytes (from 5 healthy donors) and matched epidermal melanocytes in culture. Much lower levels of α-MSH were secreted and only by the keratinocytes. Neither cell type released ACTH. Cell extracts contained signifi-cantly more ACTH than POMC, and α-MSH was detected only in keratinocytes. Nevertheless, the POMC processing components, prohormone convertases 1, 2 and regulatory protein 7B2, were detected in melanocytes and keratinocytes. In contrast, hair follicle melanocytes secreted both POMC and α-MSH, and this was enhanced in response to corticotrophin-releasing hormone (CRH) acting primarily through the CRH receptor 1. In cells stably transfected with the MC-1R, POMC stimulated cAMP, albeit with a lower potency than ACTH, α-MSH, and β-MSH. POMC also increased melanogenesis and dendricity in human pigment cells. This release of POMC from skin cells and its functional activity at the MC-1R highlight the importance of POMC processing as a key regulatory event in the skin. © FASEB.


Publication metadata

Author(s): Rousseau K, Kauser S, Pritchard LE, Warhurst A, Oliver RL, Slominski A, Wei ET, Thody AJ, Tobin DJ, White A

Publication type: Article

Publication status: Published

Journal: FASEB Journal

Year: 2007

Volume: 21

Issue: 8

Pages: 1844-1856

Print publication date: 01/06/2007

ISSN (print): 0892-6638

ISSN (electronic): 1530-6860

Publisher: Federation of American Societies for Experimental Biology

URL: http://dx.doi.org/10.1096/fj.06-7398com

DOI: 10.1096/fj.06-7398com

PubMed id: 17317724


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Funding

Funder referenceFunder name
Wellcome Trust
AR047079NIAMS NIH HHS
R01 AR047079-02NIAMS NIH HHS
R01 AR047079-03NIAMS NIH HHS
R01 AR047079NIAMS NIH HHS
R01 AR047079-01A2NIAMS NIH HHS

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