Skin POMC peptides: their actions at the human MC-1 receptor and roles in the tanning response.
The melanocortin 1 (MC-1) receptor is a key control point in the regulation of skin pigmentation. Alpha-MSH is an agonist at this receptor and through its activation regulates melanocyte function. alpha-MSH is cleaved from pro-opiomelanocortin (POMC) in the pituitary, but in humans the skin is a more important source of the peptide. Skin pigmentation is therefore regulated by locally produced alpha-MSH rather than that of pituitary origin. alpha-MSH acts as a paracrine and/or autocrine mediator of UV induced pigmentation. However, the predominant alpha-MSH in human skin is desacetyl alpha-MSH and, compared to the acetylated form, is a relatively weak agonist at the human MC-1 receptor. By acting as a partial agonist desacetyl alpha-MSH may even oppose the actions of acetylated alpha-MSH and other MC-1 receptor agonists. The most abundant MC-1 receptor agonist in human epidermis is ACTH1-17. This POMC peptide, which is produced by keratinocytes, is more potent than acetylated alpha-MSH in stimulating melanogenesis in human melanocytes and, in contrast to the latter, produces a biphasic dose-response curve. This is probably a consequence of its activation of both the cAMP and IP3/DAG signalling pathways. alpha-MSH peptides, on the other hand, selectively activate the cAMP pathway. Compared with alpha-MSH, ACTH1-17 could have the more important role as a paracrine mediator of melanogenesis and other melanocytic processes. However, ACTH1-17 is not the only POMC peptide in the skin and may interact with related peptides at the MC-1 receptor. These interactions are likely to represent important determinants of melanocyte function and skin pigmentation.
Tsatmali
M
M
Department of Biomedical Sciences, University of Bradford, United Kingdom.
Ancans
J
J
Yukitake
J
J
Thody
A J
AJ
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D006801:Humans; D008544:Melanocytes / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D018043:Receptors, Corticotropin / Q000378:metabolism*; D044101:Receptors, Melanocortin; D012867:Skin / Q000378:metabolism*; D012880:Skin Pigmentation / Q000502:physiology*; D000521:alpha-MSH / Q000378:metabolism
D010455:Peptides; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone