Researchers from the Perelman School of Medicine at the University of Pennsylvania have identified an abnormal amount a protein called Prostaglandin D2 in the bald scalp of men with male pattern baldness, a discovery that may lead directly to new treatments for the most common cause of hair loss in men. In both human and animal models, researchers found that a prostaglandin known as PGD2 and its derivative, 15-dPGJ2, inhibit hair growth. The PGD2-related inhibition occurred through a receptor called GPR44, which is a promising therapeutic target for androgenetic alopecia in both men and women with hair loss and thinning. The study is published in Science Translational Medicine.
Male pattern baldness strikes 8 of 10 men under 70 years old, and causes hair follicles to shrink and produce microscopic hairs, which grow for a shorter duration of time than normal follicles.
Researchers took an unbiased approach when scanning for potential biological causes of baldness, looking in scalp tissue from balding and non-bald spots from men with male pattern baldness and then corroborating findings in mouse models. They found that levels of PGD2 were elevated in bald scalp tissue at levels 3 times greater than what was found in comparative haired scalp of men with androgenetic alopecia. When PGD2 was added to cultured hair follicles, PGD2-treated hair was significantly shortened, while PGD2’s derivative, 15-dPGJ2, completely inhibited hair growth.
“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.” The inhibition of hair growth is triggered when the protein binds to a receptor on the cells of hair follicles.
Several known drugs that target this pathway have already been identified, he added, including some that are in clinical trials.
Something applied to the scalp to prevent baldness and possibly help hair regrow seems possible.
Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D2 synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D2 (PGD2), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD2 levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD2 inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD2 receptor G protein (heterotrimeric guanine nucleotide)–coupled receptor 44 (GPR44), but not the PGD2 receptor 1 (PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD2 in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD2 as an inhibitor of hair growth in AGA and suggest the PGD2-GPR44 pathway as a potential target for treatment.
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