Penn Medicine Study Uncovers New Pathways that Control Skin Tanning and Lightening

When skin cells responsible for pigmentation are exposed to estrogen or progesterone, the cells respond by adjusting their melanin production, resulting in either skin darkening or lightening. Although pregnant women often experience alterations in skin pigmentation, the reason for the changes has long puzzled physicians. New research, from the Perelman School of Medicine at the University of Pennsylvania, has uncovered cellular pathways in skin pigment cells that are activated by estrogen and progesterone – two of the main female sex hormones – and also identified synthetic hormone derivatives that specifically influence the pigment producing pathway. Together, the findings provide critical information that could lead to the development of new products that change skin tone without exposure to UV radiation or toxic bleaching agents. The discovery is reported today in the journal eLife.

“Correcting disorders of human skin pigmentation is difficult, as safe and effective medications that alter melanin pigment production are lacking. But, the information uncovered in this study suggests that by using derivatives of sex hormones to selectively influence the natural melanin production machinery, we may be able to develop treatments to correct such disorders,” said senior author Todd W. Ridky MD, PhD, an assistant professor of Dermatology at the Perelman School of Medicine at the University of Pennsylvania. “Further, understanding how to manipulate skin tone without the need for harmful ultraviolet radiation or toxic chemicals could have a significant impact on the cosmetic industry, as large numbers of people around the world currently spend billions of dollars in often unsuccessful or potentially dangerous attempts to lighten or darken their natural skin color. The development of drugs that specifically target the natural pigment production pathway in skin cells could be a safer and more effective alternative to the tanning beds and bleaching creams frequently used today.”

Although the molecular signals controlling skin color are varied and complex, the observation that pregnant women often experience changes in skin tone suggested to scientists that sex hormones were likely involved. However, because there are changes in the levels of many hormones and other molecules during pregnancy, it’s difficult for researchers to identify which one or which combination could be responsible for the change in pigmentation. Darkening of facial skin in pregnant women has been documented for more than 2,000 years, making this a long-standing unanswered question. But, scientists were given a clue when it was noted that women sometimes develop darker skin pigment on their face when taking birth control pills which contain only derivatives of the hormones estrogen and progesterone.

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