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Peptides and Tanning Research

01dragonslayer

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Peptides and Tanning Research​

In the western world, roughly half of women and as many as one quarter of men engage in deliberate tanning. Tanning is valued not just for its aesthetic impacts, but because it can increase vitamin D production and improve mood. The problem with tanning using ultraviolet (UV) light, however, is that it can accelerate skin aging and promote the growth of skin cancers. To avoid the detrimental effects of UV light, industry scientists have been exploring ways to replicate a tan via gels, lotions, darkening creams, cosmetics, and spray tanning. These strictly aesthetic options do not produce the same changes that UV light does. This means they don’t have the drawbacks of UV light tanning, but they also don’t have the same benefits. Most importantly, while a tan protects against further UV damage, artificial pigments and cosmetic approaches do not.

In recent decades, there has been a trend toward stimulating the natural tanning process without the aid of UV light. This new form of sunless tanning is starting to gain traction both because it creates a natural aesthetic outcome and because it is hoped that it will provide protection against the detrimental aspects of ultraviolet light exposure. Several different peptides, including melanotan (aka MT-2), have featured prominently in this cutting-edge research.



How Does UV Light Cause Tanning?​

UV light causes tanning, which is to say and increase of the skin pigment melanin, by stimulating a cellular process mediated by the tumor-suppressor gene p53[1]. The whole point of this process is to protect skin cells against UV light, which can damage DNA and lead to problems like cancer, cell death, and the breakdown of extracellular matrix proteins (e.g., collagen) in the skin. This latter effect is what leads to observable skin aging in the form of wrinkles, lines, lost elasticity, and more.

The pathway is activated when UV light damages DNA in the upper layers of the skin. The damage done to the DNA results in stabilization and activation of the p53 tumor suppressor protein. This, in turn, promotes activation of proopiomelanocortin (POMC). POMC is cleaved to product alpha-melanocyte stimulating hormone (α-MSH), which then binds to the melanocortin 1 receptor (MC1R). This causes melanocytes to both produce more melanin as well as divide and increase in number. Together, these effects cause an increase in melanin pigment leading to darkening of the skin. The melanin then absorbs the harmful UV light preventing further DNA damage[2].

Note that tanning via UV light does not occur until after DNA damage has occurred. This means that the potential for cancer development is already present before tanning occurs because DNA damage has already occurred. Therefore doctors have warned against UV-based tanning for years. The only solution, until recently, has been to avoid UV light entirely by either staying out of the sun or by wearing sunscreen. Unfortunately, recent research shows that sunscreen has problems of its own such as damaging coral reefs and potentially causing hormone dysregulation[3]. The current research is focused on promoting melanin production without exposure to UV light, thus gaining the benefits of melanin protection without first inducing DNA damage.



The New Solution to Sunless Tanning​

If scientists could stimulate tanning without the DNA damage that jumpstarts the natural process, then we could experience the benefits of tanning without any of the risks. Research into the tanning pathway has been of interest for several decades now, in part because of the discovery of melanotan and the melanocortin receptor system. Interestingly, melanotan was developed as a sunless tanning agent and then became of interest for an entirely different purpose. It’s ability to protect the skin against UV damage was almost completely forgotten as its ability to stimulate sexual arousal became the focus of melanotan research. Much later, research shifted again and melanotan became a front-runner in sunless tanning research. This peptide has since inspired the exploration and development of other peptides for sunless tanning research. Some of those peptides are discussed below along with other compounds associated with sunless tanning.





α-MSH​

Alpha-melanocyte stimulating hormone is a natural peptide hormone and agonist of the MC1R. Its role in promoting melanin production has been known since the 1960s. It is important in hair and skin pigmentation, feeding behavior, energy homeostasis, and sexual activity. It binds not only to MC1R, which is how it affects melanin production, but to the MC3R, MC4R, and MC5R as well.





Dihydroxyacetone (DHA)​

DHA is not a peptide, but rather is a saccharide or sugar. It is the primary ingredient in spray tanning products. It works by interacting with amino acids (proteins) in the keratin layer (top layer) of the skin. This reaction, called a Maillard reaction, leads to the production of pigments called melanoidins, which cause the skin to brown. While these pigments do offer some protection against UV light, the protections are minimal, and the pigments are not considered to be adequate prevention against skin damage.





Melanotan (Afamelanotide)​

Developed at the University of Arizona in the 1980s, melanotan (aka melanotan 1) is a synthetic analogue of α-MSH that is known to bind to the MC1R. It is currently used in the treatment of erythropoietic protoporphyria and has undergone clinical trial testing for the treatment and prevention of actinic keratosis, squamous cell carcinoma, and other light-related skin disorders. Melanotan is known to stimulate sexual arousal and to reduce the level of amyloid plaques in the brains of Alzheimer’s sufferers. It is also thought that it might also promote neuron growth in the brain that may lead to cognitive benefits in certain populations[4], [5]. It is one of the most important peptides in tanning research.



Melanotan 2 (MT-2)​

MT-2 is a derivative of MT-1. It has wide-ranging effects such as increasing sexual arousal, reducing compulsive behavior, protecting against diabetes, and fighting hunger. It is of particular interest for its ability to influence alcohol intake/craving[6]. Though melanotan 2 is one of the peptides that has been extensively researched in sunless tanning, its sexual effects have been of predominant interest among researchers. In particular, the peptide is being investigated as an alternative to phosphodiesterase inhibitors, such as Viagra, especially among men who do not respond to other treatments[7].



PT-141 (Bremelanotide)​

Currently marketed under the name Vyleesi for the treatment of female hypoactive sexual desire disorder (HSDD), PT-141 is a metabolite of MT-2 and thus a derivative of α-MSH. It has been associated with changes in blood pressure but does not interact with alcohol. This latter effect distinguishes it from flibanserin (Addyi), which is also indicated for HSDD. Flibanserin is not a peptide and does not promote changes in skin pigmentation. Of note, PT-141 only causes skin pigmentation if used at certain doses and for certain lengths of time. Research shows that, at low does, PT-141 primarily affects sexual arousal[8], [9]. When used at higher doses or for prolonged periods, PT-141 will cause skin darkening. Peptides and tanning research have virtually ignored PT-141 as the primary focus has been on its benefits to sexual arousal.



Peptides and Tanning Research: Summary​

Peptides and tanning research are really in their infancy. While a handful of peptides have been shown to produce skin pigmentation, many have been investigated more thoroughly for their secondary effects. This leaves a dearth of research into the area of sunless tanning. For those interested in peptides and tanning research, the field is wide open for innovation. Of particular interest is the development of a peptide tanning agent that does not have off-target melanocortin receptor effects. There is a lot of promise not just for cancer prevention, but for aesthetics and for the prevention of sunburns as well in peptides and tanning research.
 
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