L. Garza, Yaping Liu, Zaixin Yang
Mar 21, 2012
Citations
15
Influential Citations
245
Citations
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Journal
Science Translational Medicine
Abstract
Prostaglandin D2 inhibits hair growth through its receptor, GPR44, and this pathway could serve as a new target for developing treatments for male pattern baldness. A Not-So-Hairy Situation Everybody wishes his or her hair was different; curly hair wants straight locks, straight hair desires some curl. Patients with androgenetic alopecia (AGA), however, would take either one, as long as it meant having hair. AGA is a disorder that affects both men and women, leading to hair thinning and loss. Here, Garza and colleagues provide new insight into the pathogenesis of AGA, in hopes of developing new therapeutics that target specific pathways responsible for baldness. The authors first examined bald and haired scalp from five men with AGA and showed that the enzyme prostaglandin D2 (PGD2) synthase was elevated at the mRNA and protein levels in bald scalp only. In a larger group of 17 men, they confirmed that the synthase product PGD2 was also elevated in bald versus haired scalp. In mice with synchronized hair follicle cycling, Garza et al. uncovered a temporal relationship between PGD2 gene expression and hair follicle regression. The authors further found that PGD2 and a related metabolite, 15-dPGJ2, inhibited hair growth in both mice and human hair follicles, providing a crucial functional link between the prostaglandin pathway and AGA. Garza and coauthors identified the receptor GPR44 to be responsible for mediating the negative effects of PGD2. By discovering such therapeutic targets for downstream drug development, such as a topical treatment, Garza et al. may have given patients with AGA a long-awaited choice: curly or straight? 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.