Researchers Uncover Clue To Baldness, Could Lead To Cure
March 22, 2012

Researchers Uncover Clue To Baldness, Could Lead To Cure

Male baldness, long considered the bane of men all over the world, may become a thing of the past after researchers found a biological clue that could raise the prospect of stopping and perhaps even reversing hair loss.

The researchers, from University of Pennsylvania's Perelman School of Medicine, have identified an abnormal amount of protein called Prostaglandin D2 (PGD2) in the bald scalp of men with male pattern baldness. Lab studies were conducted using mice and cultured human hair follicles.

In both human and animal models, the team found that PGD2 and its derivative, 15-dPGJ2, inhibit hair growth. The inhibition occurred through a receptor called GPR44, which could be a promising therapeutic treatment for androgenetic alopecia in both men and women with thinning hair.

Among men with androgenetic alopecia (AGA), bald scalp tissue had elevated levels of PGD2 compared with hair-covered tissue from the same individual, said George Cotsarelis, MD and colleagues.

The researchers reported yesterday (March 21) in the journal Science Translational Medicine that drugs are already being developed that target the pathways associated with hair loss. The hope is that the findings lead to a cure for baldness.

Most men begin to go bald in middle age, with nearly 80 percent of men experiencing at least some hair loss by age 70. In men, testosterone plays a major role in hair loss, as do genetic factors, causing hair follicles to shrink and eventually becoming so small they are invisible, leading to the appearance of baldness.

“Our findings should lead directly to new treatments for the most common cause of hair loss in men, androgenetic alopecia,” the team wrote.

However, it remains unclear if blocking the GPR44 receptor would allow hair to regrow after balding, or if it would just prevent further balding. It also remains unclear whether inhibiting the receptor would have any effect in humans at all.

To explore that possibility, Cotsarelis and his colleagues examined scalp tissue in 22 white men between 40 and 65 who underwent hair transplantation for male pattern baldness. None of the men were taking either of two approved medications for baldness -- minoxidil and finasteride.

The researchers found through genetic analysis that levels of PGD2 were three times higher in bald scalp tissue than in hair-covered scalp.

To further test the possibilities and better understand the significance of their finding, they turned to experimental studies involving mice. In normal mice, they found an association between the increase in PGD2 and the regression of hair follicles during normal hair cycling.

In mice engineered to have elevated of PGD2 in the skin, they developed alopecia, miniaturization of follicles, and sebaceous gland hyperplasia -- all characteristics associated in human baldness.

“The next step would be to screen for compounds that affect this receptor and to also find out whether blocking that receptor would reverse balding or just prevent balding - a question that would take a while to figure out,” Cotsarelis told Helen Briggs of BBC News.

“Although a different prostaglandin was known to increase hair growth, our findings were unexpected, as prostaglandins haven´t been thought about in relation to hair loss, yet it made sense that there was an inhibitor of hair growth, based on our earlier work looking at hair follicle stem cells,” he added.

Prostaglandins are well characterized for their role in many bodily functions, including controlling cell growth and dilating smooth muscle tissue. It was shocking to find that PGD2 inhibited hair growth while prostaglandin F2alpha is known to increase hair growth.

“The question of whether similar changes in PGD2 levels are found in the affected scalp of women with androgenetic alopecia also needs to be addressed,” the team wrote. Future studies, potentially testing topical treatments that may target GPR44, can determine whether targeting prostaglandins will benefit woman with AGA as well.

Cotsarelis´ study was funded by the National Institutes of Health, the Skin Disease Research Center, the Pennsylvania Department of Health, the Edwin and Fannie Gray Hall Center for Human Appearance at University of Pennsylvania Medical Center, the American Skin Association, the Dermatology Foundation, and L´Oreal.

Cotsarelis is also a co-inventor of a patent owned by UPenn describing the PGD2 pathway as a target for inhibiting hair loss, among other claims.