Human skin contains specialized cells, called melanocytes, which are located at the base of the epidermis. These cells are programmed to manufacture a brown pigment, called melanin, in response to exposure of skin to sunlight. Since melanin acts as a sunscreen, the production of this pigment by melanocytes is a defense response of the skin to the damaging and potential skin cancer causing rays of the sun. In addition to UV radiation, other factors can stimulate melanocytes to make melanin. Hormones, such as those in birth control pills can cause melanocyte “activation”, and exposure of the skin to any event that causes inflammation, such as acne, dermatitis, exposure to chemicals, etc., can also result in increased melanin production by melanocytes. Melanin production in human melanocytes is controlled primarily by the rate-limiting enzyme for melanin synthesis, tyrosinase, which catalyzes the hydroxylation of tyrosine to L-DOPA and the oxidation of L-DOPA to dopaquinone. The subsequent steps in the pathway to melanin formation can occur non-enzymatically although two additional melanocyte-specific enzymes are thought to play a role in determining what type of melanin is formed. The chart on the left shows that the pathway can diverge to produce either a red/yellow type of melanin (pheomelanin), or brown/black melanin, called eumelanin. The type of melanin made is genetically determined, and results in some people having fair skin and red hair while others are dark-skinned and have dark hair. The melanin produced by the action of tyrosinase is “packaged” within the melanocyte into unique vesicles called melanosomes. These organelles are then transferred from the melanocyte to surrounding keratinocytes in the skin. As keratinocytes move from the lower part of the epidermis up to the surface, they can carry the ingested melanosomes with them, and the result is a deposition of the melanin-filled melanosomes near the skin’s surface. This is what gives the skin its brownish tint. The image on the right shows a melanocyte and the production of melanosomes.