ECE2006 Poster Presentations Neuroendocrinology and behaviour (70 abstracts)
Pro-opiomelanocortin and ACTH, precursors of alphaMSH, are secreted from human melanocytes and keratinocytes and can stimulate melanogenesis
K Rousseau 1 , S Kauser 2 , LE Prtichard 3 , A Warhurst 1 , RL Oliver 1 , CA Schmitz 3 , AJ Thody 2 , DJ Tobin 2 & A White 1
1University of Manchester, Manchester, United Kingdom; 2University of Bradford, Bradford, United Kingdom; 3AstraZeneca, Alderley Park, United Kingdom.
Pro-opiomelanocortin (POMC) is endoproteolysed to ACTH and alpha MSH which bind to the melanocortin-1 receptor, (MC-1R), and act as principal mediators of human skin pigmentation. In addition there is increasing evidence that alpha MSH has important anti-inflammatory actions in the skin. The aim of this study was to determine the efficiency of processing and the involvement of the different peptides in melanogenesis. To address this question we utilized specific two-site immunometric assays for POMC and ACTH and a sensitive immunoassay for alpha MSH.
Human epidermal melanocytes from five different volunteers had significant quantities of POMC and ACTH within the cells with no detectable alpha MSH. Under basal conditions where there is constitutive secretion of peptides, only POMC was detected in the medium. Matched epidermal keratinocyte cultures contained higher levels of POMC and ACTH and low but significant levels of alpha MSH in the cells. In contrast to melanocytes, the keratinocytes did secrete alpha MSH although much higher levels of POMC were released into the medium.
In order to investigate whether POMC was able to bind to the MC-1R and induce melanogenesis, we affinity purified POMC from human small cell lung cancer cells. Using CHOK1 cells stably transfected with the MC-1R and a cAMP reporter construct, we found that POMC could activate the MC1R with a similar potency to gamma MSH but with significantly lower potency than ACTH, alpha MSH and beta MSH. Interestingly, POMC also induced melanogenesis in S91 mouse melanoma cells albeit at 100 fold higher concentrations than alpha MSH.
In summary, under steady state conditions there is relatively little secretion of the more potent melanogenic peptides from keratinocytes and none from melanocytes. This suggests that processing of POMC may be a key regulatory event in order to generate potent bioactive peptides involved in human pigmentation and immunomodulation in the skin.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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