Skin POMC peptides: their actions at the human MC-1 receptor and roles in the tanning response
Abstract
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.
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The melanocortin system also plays an important role in regulating sympathetic nervous system activity and blood pressure besides its effects on food intake and body weight regulation.
“Besides its effects on food intake and body weight regulation, the melanocortin system also plays an important role in regulating SNS activity and BP.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [5]
Melanocortins play an important role in regulating blood pressure and sympathetic nervous system activity as well as energy balance, glucose and other metabolic functions in humans and experimental animals.
“Melanocortins play an important role in regulating blood pressure (BP) and sympathetic nervous system (SNS) activity as well as energy balance, glucose and other metabolic functions in humans and experimental animals.”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [5]
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- Authors
- TSATMALI, M., ANCANS, J., YUKITAKE, J., & THODY, A. J.
- Affiliations
- University of Bradford (GB)
- Venue
- Pigment Cell Research
- Publisher
- Wiley
- Published
- 2000-06
- Volume
- 13
- Issue
- s8
- Pages
- 125-129
- ISSN
- 0893-5785 (ISSN-L)
- 1600-0749
- OpenAlex
- W2041150906
- Cited by
- 61
- References
- 0
- Citations by year
- 2026: 1 · 2024: 2 · 2022: 1 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 1
- FWCI
- 0.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pigment Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- MC1R, proopiomelanocortin, alpha-melanocyte-stimulating hormone, skin pigmentation, tanning, melanogenesis, melanocytes, UV-induced pigmentation, cAMP signaling, paracrine signaling, keratinocytes, partial agonists
- MeSH terms
- Adrenocorticotropic Hormone, alpha-MSH, Animals, Humans, Melanocytes, Peptides, Pro-Opiomelanocortin, Skin, Skin Pigmentation, Receptors, Corticotropin, Receptors, Melanocortin
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