The yin and yang of male pattern baldness

A cousin of a molecule that stimulates eyelash growth may stop hair growth on the scalp

Just because a man is bald doesn’t mean there’s nothing going on in his scalp. A molecule found in the scalps of bald men may offer clues about how male pattern baldness arises and what to do about it.

A lipid called prostaglandin D2 (green) is made by cells in human hair follicles like this one. A new study shows that the the hormone-like molecule inhibits stem cells (red) needed to make hair grow. Courtesy of Luis Garza and George Cotsarelis

Men with male pattern baldness have higher levels of a molecule called prostaglandin D2 in the bald parts of their scalps than in parts still covered in hair, a new study shows. Prostaglandin D2 stops the growth of stem cells that give rise to hair follicles, stem cell biologist George Cotsarelis of the Perelman Center for Advanced Medicine at the University of Pennsylvania in Philadelphia and colleagues report in the March 21 Science Translational Medicine.

Cotsarelis’ group had previously found that bald men still have hair follicle stem cells, but that those cells are dormant in bald areas of the head. The researchers reasoned that either the stem cells lacked growth stimuli or an inhibitor prevented the cells from growing.

To find out which, the team analyzed gene activity in scalp samples taken from men undergoing hair transplant procedures. The researchers found 81 genes with higher activity in bald portions of the scalp compared with areas covered in hair. Among the more active genes was one that makes prostaglandin D2, suggesting that the molecule might be holding back hair growth.

Other researchers had previously found that a different prostaglandin called F2alpha stimulates growth of eyelashes. “Prostaglandins often have a yin and a yang,” Cotsarelis says: One prostaglandin may stimulate hair growth, but another might stop it.

In the new study, prostaglandin D2 inhibited hair growth in human hair follicles in the lab and slowed hair growth in mice when applied to the mice’s skin. And mice genetically engineered to make a lot of prostaglandin D2 in the skin go bald.

Prostaglandin D2 works in the stem cells through a protein called GPR44. That protein, a receptor, sets off a biochemical chain reaction when it detects the presence of prostaglandin D2. Hair growth in mice that lack the receptor wasn’t inhibited by prostaglandin D2, suggesting that drugs that block GPR44 might help treat baldness, the team concludes.

That doesn’t mean a cure for baldness is right around the corner, says Kurt Stenn, a hair biologist at the Aderans Research Institute in Marietta, Ga. “Bald people will have to be patient a little longer,” he says. The study raises many questions, including why levels of prostaglandin D2 increase in the first place, how the molecule interacts with testosterone (which is known to be necessary for male pattern baldness), and which other proteins might be involved in the balding process, Stenn says. “It’s a beginning study, but a wonderful beginning study.”

Researchers have had many clues that prostaglandins might be involved in hair growth, says Bruno Bernard, a biologist who heads research on hair for the L’Oreal company in Clichy, France. The popular hair growth stimulator minoxidil (the active ingredient in Rogaine) activates an enzyme that makes prostaglandins, suggesting that hair growth is controlled by a balance between competing prostaglandins.

“To me there will be no single cure for baldness,” Bernard says. “I’m personally convinced the future will be a combination of agents.”

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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