Then and Now: Pigmentation Update


I have written two articles for Skin Inc. on pigmentation, the last being published in March 2009.1,2 Much has transpired in pigmentation research in the last 10 years; however, this short article cannot do justice to all new research. Therefore, we shall highlight just the most important new findings and refer you to several comprehensive references on pigmentation.

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UPDATE 1: Melanocyte Life Cycle

The life cycle of the melanocyte has several stages:

  • Differentiation in the neural crest,
  • Migration and proliferation of the melanoblast into the melanocyte,
  • Proliferation and maturation of the melanocyte in the target tissue,
  • Activation of melanogenic enzymes, and finally
  • Transfer of the melanosomes into the keratinocytes.3

The origin of the melanocyte in mammals start from cells in the neural crest of the embryo. This is the part of the embryo in which the nervous system will develop. The melanoblasts must migrate from the neural crest to their new home in the eyes or in the skin. Since the melanocyte must travel through different types of tissue, it must be protected from attack by the immune system. This is why pigmented cancer cells metastasize so rapid. An excellent article on this topic is by RL Mort et al.4

UPDATE 2: Melanosome Transfer

Within the skin, one melanocyte is able to supply 36 keratinocytes with melanosomes. The transfer of the melanosome is quite complex, and the process is not fully understood. Below are some of the latest research on how this happens.

1. The dendrite of the melanocyte contains multiple melanosomes that are surrounded by a membrane that contains a few mitochondria that are formed in the filopodium of the dendrite.

2. The melanosomes are released into different areas of the extracellular space within the dendrite.

3. After transfer, the melanosomes are captured by the microvilli of the keratinocytes, which then react with a protease activating receptor.

4. Protease degrades the membrane and releases the melanosomes. Single melanosomes are released into the cytoplasm of the keratinocytes.

How the number and size of melanocytes and melanosomes are regulated remains unknown. We do know that the keratinocytes, the melanocyte, and the fibroblasts are all involved in production of melanin, which involves many cells creating signaling substances. Some years ago, there was an introduction of theory known as the three-enzyme cascade for the initiation of melanogenesis called the modified Raper-Mason Scheme. This is an interesting concept that you can read more about in a paper by Schallreuter et al.5 Some new work on the role of estrogen and a condition known as melasma will be discussed next.

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UPDATE 3: Melasma

Melasma is a common disorder seen in women both in pregnancy and in the non-pregnant state. The exact cause remains unknown, but there are contributing factors that have been identified. No specific treatment has been developed to date. It appears that pregnancy and the use of estrogen containing oral contraceptives are heavily implicated in the pathogenesis of melasma. The condition is also more common in darker skinned individuals. Melasma occurs in 10–15% of pregnant women and in 10–25% of women taking oral contraceptives. There is a high incidence of melasma in family members, suggesting a possible genetic predisposition. Much research is being done in this area.

UPDATE 4: Estrogen and Pigmentation

A number of researchers believe that estrogen stimulates the melanocyte to produce more melanin. However, a recent study shows there are no receptors in the melanocyte for estrogen. This is a critical finding because the hormone effect cannot happen in a cell unless there is a receptor for that hormone somewhere on the cell membrane or within the cell. These researchers discovered an interesting pathway by which estrogen can stimulate the production of melanin in the melanocyte. Understanding this requires knowledge of molecular biology, but the cell contains many types of receptors for hormones and all kinds of intercell signals. Without cell receptors, no action could take place. However, there is a type of receptor on many cells studies that is an ancient type of receptor known as 7 -transmembrane pass. It is a family of 11 human genes and has been named PAQR; you just need to remember that this is a new family of genes. This family allows the estrogen hormone to bypass the need for a specific receptor and to stimulate another receptor that carries the message into the cell. If you want to read further about this process see the paper by Natale, CA et al.6

UPDATE 5: Stay On Top

In summary, the science of pigmentation is moving ahead fast, and the information is becoming increasingly more complex. To be able to keep up and follow it means the reader must have a knowledge of molecular biology. This is an exciting and interesting topic and has many applications for the knowledgeable esthetician.


  1. Physiology of the Skin: Pigmentation, Skin Inc. May 1991.
  2. Physiology of the Skin: Pigmentation Revisited, Skin Inc., March 2009
  3. M Cichorek, M Wachulska, A Stasiewicz and A Tymińska, Skin melanocytes: Biology and development, Postepy Dermatol Alergol 30(1):30-41 (2013)
  4. RL Mort, IJ Jackson and EE Patton, The melanocyte lineage in development and disease, Development 142, 620–632 (2015)
  5. KU Schallreuter, S Kothari, B Chavan and JD Spencer, Regulation of melanogenesis: Controversies and new concepts, Exp Dermatol May 17(5) 395-404 (2008)
  6. CA Natale, EK Duperret and J Zhang et al., Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors, Bronner ME, ed. eLife.2016;5:e15104.

Electron microscope micrograph of melanin granules (dark blue) in a melanocyte (yellow) and in a keratinocyte (light blue) with keratin (red)

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Peter T. Pugliese, M.D. practiced family medicine before dedicating over 40 years to the science of skin and aging. He is the founder of Circadia by Dr. Pugliese, as well as the author of Advanced Professional Skin Care and Physiology of the Skin.

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