Scientists have uncovered how human skin cells control pigmentation — a discovery that could lead to safer ways to tan or lighten the skin.
Researchers found that skin color can be regulated by estrogen and progesterone, two of the main female sex hormones. Estrogen darkens the skin; progesterone lightens the skin. Although this much was known to a limited degree, the new research revealed two cellular receptors that appear to control this process in skin cells called melanocytes.
But the researchers also identified two molecules similar to estrogen and progesterone that could activate these receptors to induce tanning and lightening, respectively, without triggering any other bodily changes normally associated with these sex hormones.
Creams containing these molecules may someday help people who have medical conditions causing uneven skin tones or who, for cosmetic reasons, want to darken or lighten their skin without exposure to UV radiation or toxic bleaching agents, according to the researchers, whose study is published today (April 26) in the journal eLife. [5 Things You Must Know About Skin Cancer]
The research is based on a phenomenon that has been observed for millennia: that women's skin tends to change color during pregnancy. Hippocrates, a Greek physician who lived 2,400 years ago, noticed the blotchy spots that can appear on a pregnant woman's body and thought, albeit incorrectly, that the spots were related to the gender of the child.
Modern scientists have made the association between pigment changes and sex hormones. Indeed, one side effect of the application of estrogen creams is skin darkening.
But precisely how these sex hormones affect skin pigmentation has been a long-standing question, said Dr. Todd Ridky, senior author of the new findings and an assistant professor of dermatology at the University of Pennsylvania.
Suntans work completely differently: Ultraviolet radiation from the sun or tanning booths trigger an increase in a hormone called melanocyte-stimulating hormone (MSH) in the skin, Ridky said. The MSH binds to a receptor on melanocyte skin cells called MC1R and makes these cells produce melanin, which darkens the skin.
But researchers have been stumped by how sex hormones can enhance or lessen skin pigmentation, because neither estrogen nor progesterone works through MC1R.
"If you expose melanocytes to estrogen, they respond by making more melanin, but they don't have the classic estrogen receptor," Ridky told Live Science. "So, that got us really interested. How the heck is this working, then?" [The 7 Biggest Mysteries of the Human Body]
By studying human skin cells both in a petri dish and in a 3D-bioengineered patch of skin about the size of a postage stamp, Ridky's team discovered a different, unexpected set of receptors on melanocytes that do interact with the sex hormones. Specifically, they found a receptor called GPER that interacts with estrogen and triggers melanin production, and a receptor called PAQR7 that interacts with progesterone and decreases melanin production.
Next, the team identified two molecules that are similar to estrogen and progesterone and that could activate the GPER and PAQR7 receptors, respectively, without tickling any other known estrogen or progesterone cellular receptor on the cells. This may imply that these molecules could induce the desired tanning or lightening effects, without the unwanted side effects associated with estrogen and progesterone.
When the researchers applied these molecules in a topical solution to the ears of mice, they saw noticeable changes in the mice's skin pigmentation.
Ridky said that topical creams based on these molecules might someday help people with pigment disorders, including vitiligo, an autoimmune condition in which some parts of the skin lose their ability to make melanin. (Pop star Michael Jackson had vitiligo.) An estrogen-like cream could help darken the skin. Conversely, a progesterone-like cream could lighten dark spots caused by acne or other skin conditions.
For cosmetic reasons, many people want to darken or lighten their skin. Creams based on today's discoveries could one day alter skin tone more safely than current methods for doing so — that is, cancer-inducing UV rays to tan or toxic chemicals to lighten.
But initiating clinical studies to test the safety of the creams may take some time, Ridky said. Both receptors are relatively new to physicians, and the specific agents that activate them have not been studied in people. Ridky indicated that the work was in its initial stages.
"We are beginning to see that melanocytes integrate signals from several receptors to modulate pigment production, which will help us build a more complete model of how pigmentation is regulated," said Christopher Natale, a graduate student on the team who discovered the new receptors, and the first author of the study.
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