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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 4 of 12

Pheomelanin is not able to withstand UV radiation, tends to break down into photosensitizing compounds and also generates free radicals. There is a certain amount of pheomelanin in most individuals, more in those with Fitzgerald Skin Type I and less in those with Type IV skin.2, 3 The relative amounts of eumelanin to pheomelanin may determine an individual’s susceptibility to UV light and skin cancer.

Just a note on hair color: Lack of pheomelanin means no red hair. MC1R decides which pigment gets made, while other genes decide in what amounts. A strawberry blonde hair color inherits two badly functioning MC1R genes and, depending on how well they work, some individuals will have dark or light red hair. Blondes have only a little pheomelanin, but enough to produce a light hair color without red tones.

What controls melanin production? This question is one everyone wants to know the answer to if they are interested in skin-lightening agents and pigmentation disorders. Just like everything else about pigment formation, all the answers are not known yet, but a great deal of research is underway throughout the world.

The control of melanogenesis

Why does the skin around a pimple become a darker color? Why is pregnancy associated with increased pigmentation? The key elements in the regulation of melanogenesis are believed to be represented by tyrosinase and tyrosine transporter protein (TyrP). This regulation is quite complex as evidenced by the large number of genes and associated binding sites of an additional large family of transcription factors.j Much of this can be boiled down to one step at the intracellular level, because the major regulatory pathway involves a common mediator, cyclic adenosine monophosphate (cAMP), which is also known as a second messenger. In addition, both tyrosine and L-DOPA are themselves regulators of melanogenesis.

Let’s start with the melanocyte. It needs messengers to tell it to make melanin; so, what are these messengers? Well, there are a lot of them, but they can be divided into groups to make it easier to remember. Microphthalmia-associated transcription factor (MITF), proopiomelanocortin (POMC), which gives rise to melanocyte-stimulating hormone (MSH), adrenocorticotrophins (ACTH) and beta-endorphins, catecholamines, acetylcholine and estrogen, to name just a few.4, 5, 6, 7 To cover each one of these agents and how they work would require much more detailed biochemistry, but for the sake of this discussion, they can be lumped into a single pathway, the aforementioned cAMP.