Alpha-Melanocyte Stimulating Hormone (α-MSH) is a peptide hormone produced in the body. It is part of a family of peptides known as melanocortins, all of which are cleaved from the precursor proopiomelanocortin (POMC) peptide and bind to specific melanocortin receptors throughout the body. Alpha-MSH consists of 13 amino acids, with the sequence Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val.
Of the five known melanocortin receptors, α-MSH binds with various affinities to MC1R, MC3R, MC4R and MC5R. When bound to each of these receptors it is believed to have roles in: regulating pigmentation and inflammation; energy homeostasis and sexual behavior; appetite regulation; and exocrine function, respectively.
Alpha-Melanocyte Stimulating Hormone in the skin
It is α-MSH’s role regulating pigment (melanin) in the skin which is arguably best understood. In the skin, α-MSH is produced by epidermal skin cells (keratinocytes and, less commonly, melanocytes and Langerhans cells) as a protective response to damage caused by ultraviolet (UV) radiation.
Alpha-MSH molecules then bind with the MC1R on melanocytes (pigment producing cell) to activate the production of melanin (via a series of chemical reactions known as a signaling pathway). Following this process, melanin granules are deposited in packages called melanosomes which are then transported to the ends of the melanocyte projections, called dendrites.
The tips of these dendrites are then enveloped by nearby keratinocytes into which the melanin granules are released. These spread out to form a pigmented, protective barrier over the keratinocyte’s nucleus. The melanin acts to shield this cell from further UV damage by absorbing, reflecting and refracting light.
Melanocortin receptors - expression and influence
In addition to activating melanin, α-MSH is known to have several other roles in the skin, although the exact mechanisms are not fully understood. Recent research has shown that α-MSH enhances the repair of DNA damage (such as cyclobutane pyrimidine dimers or CPDs) – a process known as nucleotide excision repair or NER – and reduces the generation of free radicals (particularly hydrogen peroxide) following UVR impact. Both of these factors reduce the overall damage caused by UVR, thus reducing the risk factors for certain skin cancers. One mitigating factor, however, is that α-MSH must be able to bind to the MC1R to achieve this function. In some fairer skin types, and in individuals with mutations or damage to the MC1R, the normal response when α-MSH binds to the MC1R is significantly impaired or absent. Alpha-MSH is also known to play a role in inhibiting both the expression and activity of pro-inflammatory molecules (cytokines) in the skin.
- Bohm, M et al (2005). “?-Melanocyte-stimulating Hormone Protects from Ultraviolet Radiation-induced Apoptosis and DNA damage”. Jour Biol Chem. 280(7):5795-5802.
- Hedley, S et al (1998). “α-MSH and Melanogenesis in Normal Human Adult Melanocytes”. Pigment Cell Res. 11:45-56.
- Song X et al (2009). “Alpha-MSH Activates Immediate Defense Responses to UV Induced Oxidative Stress in Human Melanocytes” Pig Cell Mel Res. 22(6):809-818. Available online: http://onlinelibrary.wiley.com/doi/10.1111/j.1755-148X.2009.00615.x/pdf>