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Pigmentation is highly heritable, being regulated by genetic, environmental, and endocrine factors that modulate the amount, type, and distribution of melanins in the skin, hair, and eyes. In addition to its roles in camouflage, heat regulation, and cosmetic variation, melanin protects against UV radiation and thus is an important defense system in human skin against harmful factors. Being the largest organ of the body that is always under the influence of internal and external factors, the skin often reacts to those agents by modifying the constitutive pigmentation pattern. The focus of this review is to provide an updated overview of important physiological and biological factors that increase pigmentation and the mechanisms by which they do so. We consider endo\u2010crine factors that induce temporary (\n                    <jats:italic>e.g.<\/jats:italic>\n                    , during pregnancy) or permanent (\n                    <jats:italic>e.<\/jats:italic>\n                    <jats:italic>g.<\/jats:italic>\n                    , during aging) changes in skin color, environmental factors (\n                    <jats:italic>e.g.<\/jats:italic>\n                    , UV), certain drugs, and chemical compounds,\n                    <jats:italic>etc.<\/jats:italic>\n                    Understanding the mechanisms by which different factors and compounds induce melanogenesis is of great interest phar\u2010maceutically (as therapy for pigmentary diseases) and cosmeceutically\n                    <jats:italic>(e.g.<\/jats:italic>\n                    , to design tanning products with potential to reduce skin cancer risk).\u2014Costin, G\u2010E., Hearing, V. J. Human skin pigmentation: melanocytes modulate skin color in response to stress.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    21, 976\u2013994 (2007)\n                  <\/jats:p>","DOI":"10.1096\/fj.06-6649rev","type":"journal-article","created":{"date-parts":[[2007,1,22]],"date-time":"2007-01-22T20:51:31Z","timestamp":1169499091000},"page":"976-994","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":820,"title":["Human skin pigmentation: melanocytes modulate skin color in response to stress"],"prefix":"10.1096","volume":"21","author":[{"given":"Gertrude-E.","family":"Costin","sequence":"first","affiliation":[{"name":"Global R&amp;D, Avon Products, Inc. New Technology Department Suffern New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent J.","family":"Hearing","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology National Cancer Institute National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,1,22]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"70","volume-title":"Fitzpatrick's Dermatology in General Medicine","author":"Haake A.","year":"1999"},{"key":"e_1_2_7_3_1","first-page":"125","volume-title":"Melanin: Its Role in Human Photoprotection","author":"Pathak M. A.","year":"1995"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1039\/B505793K","article-title":"Biochemistry of the skin\u2014our brain on the outside","volume":"35","author":"Tobin D.J.","year":"2006","journal-title":"Chem. Soc. 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