14 DAY TRIAL // Researchers from the Massachusetts General Hospital (MGH) Cutaneous Biology Research Center (CBRC) have found a switch that blocks the natural pigmentation of the skin, and this discovery could lead to a new way of protecting the skin, thus reducing cancer risks.
They say that blocking the action of this enzyme called PDE-4D3 in ice, led to a significant increase of melanin production.
David Fisher, MD, PhD, director of the hospital's Department of Dermatology, an investigator at the MGH CBRC, and leader of the study, explains that “the primary goal of inducing melanin production in human skin would be prevention of skin cancer, since all the common forms are known to be associated with UV exposure.
“Not only would increased melanin directly block UV radiation, but an alternative way to activate the tanning response could help dissuade people from sun tanning or indoor tanning, both of which are known to raise skin cancer risk.”
Four years ago, Fisher's team proved that the metabolic pathway leading to UV-induced pigmentation is controlled by cyclic AMP (cAMP), a molecule that carries messages from the cell surface to internal target molecules.
After using a strain of transgenic mice – with red hair and melanocytes in their epidermis, the researchers discovered that cAMP production within animal skin led to strong pigmentation.
The problem with this experiment is that the drug they used in that study cannot penetrate human skin, so they had to find another approach.
Most drugs block target molecules so it is necessary to better define the path between UV exposure and melanin production, in order to alter whatever limits melanin production and increase the amount of the pigment.
cAMP carries signals whose strength and duration are controlled by PDE enzymes, that break down the molecule after it delivers the message, and a detailed study revealed that PDE-4D3 was the regulator of cAMP activity in melanocytes.
The scientists tested the role of PDE-4D3 in melanin control on transgenic mice with epidermal melanocytes and five days later the animals' skin had become darker.
Fisher explains that “although PDE enzymes degrade cAMP within all cells, different members of this enzyme family are active in different types of cells.
“We showed that PDE-4D3 is particularly important within melanocytes, and while the enzyme may have a role in other cells, a blocking drug that is applied directly to the skin would probably have limited effects in other tissues.”
More research is necessary in order to develop drugs that can penetrate human skin and safely block PDE-4D3, he adds.
The findings are reported in the journal Genes & Development.