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Pigmentation Revisited

By: Peter T. Pugliese, MD
Posted: February 26, 2009, from the March 2009 issue of Skin Inc. magazine.

page 6 of 12

The melanosomes are transferred to the keratinocyte through the filopodia; after this, what happens next is uncertain. Some scientists believe the melanosomes are removed from the filopodia by a process called exocytosis; that is, the melanosomes are shed into the cytoplasm by being forced out of the filopodia. The keratinocyte gather these melanosomes up by a process called endocytosis, surrounding them with a cell membrane and pulling them into the cytoplasm of the keratinocyte. Another group of scientists believe that the filopodia actually enter the membrane and the keratinocyte, and deposit the melanosomes inside the keratinocyte. At present, no one is sure who is right.15, 16

After the melanosomes enter the keratinocyte, they are transported to the centrosome of the nucleus, which points upward to protect the DNA in the nucleus from UV radiation. As the keratinocyte moves upward to the stratum corneum, the melanosomes will degrade in time and new cells will take the place of the exfoliated cells. This is the end of their journey. The complex process known as melanogenesis, which requires almost a hundred genes and many enzyme reactions, draws to a close. All of the defects in pigment are related to a defect in one of the genes. When you look at skin, eye or hair color, consider all the biological processes that are involved in just that one aspect of human development. Scientists have been studying skin pigment for more than 100 years and still there are many unanswered questions.

Practical application

Every esthetician knows that there are many types of pigment problems, and with the information in this article, the source of many of these problems will become apparent. For example, take the condition known as albinism, a lack of melanin production caused by a defective tyrosinase enzyme. There are many types of albinism and not all of them have been fully identified as to biological mechanisms. When the esthetician sees a pigmentation problem, the first question to be answered is: Is this a primary melanocyte problem, a melanin production problem, a melanosome transfer problem, a genetic origin or an environmental origin? Knowing the answer to these questions will help the esthetician address the problem.

The major target in reducing pigmentation is the enzyme tyrosinase, since it is the key enzyme in the production of melanin. Many agents are available to block the actin tyrosinase, as well as various other sites in the melanogenesis pathway. A second approach is to block the stimulators of tyrosine. MSH is one key stimulator that can be inhibited with a phony peptide designed to tie up the MSH receptor on the cell. A third way is to inhibit the transfer of melanosomes to the keratinocyte and one agent known to do just that is niacinamide. A fourth way is to exfoliate the stratum corneum cells to remove those that contain melanin. Above all, using sunscreen and staying out of high UV exposure areas, such as beaches and snowy areas, are the most effective means of limiting melanin formation. By knowing the various steps that are necessary to form melanin, you can plan a skin-lightener program by choosing a combination of agents that inhibit melanin at several production points.


a Differentiation is a biological process in which a cell becomes more specialized and more defined.