Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.
Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.
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DOI：
10.1126/scitranslmed.3003122
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发表时间：
2012-03-21
影响因子：
17.1
通讯作者：
Cotsarelis G
中科院分区：
文献类型：
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作者：
Garza LA;Liu Y;Yang Z;Alagesan B;Lawson JA;Norberg SM;Loy DE;Zhao T;Blatt HB;Stanton DC;Carrasco L;Ahluwalia G;Fischer SM;FitzGerald GA;Cotsarelis G
特氟沙星是发展男性型秃发所必需的，称为雄激素性脱发（阿加）;然而，这种疾病中头发生长减少的机制尚不清楚。我们发现，前列腺素D2合成酶（PTGDS）的mRNA和蛋白质水平的升高，在秃头头皮相比，头发头皮的男性阿加。PTGDS酶活性的产物前列腺素D2（PGD 2）在秃头中也同样升高。在小鼠的正常毛囊周期中，Ptgds和PGD 2水平在消退阶段之前立即增加，表明对毛发生长的抑制作用。我们表明，PGD 2可以抑制移植的人类毛囊中的毛发生长，并且局部应用于小鼠时也可以抑制毛发生长。毛发生长抑制需要PGD 2受体G蛋白（异源三聚体鸟嘌呤核苷酸）偶联受体44（GPR 44），但不需要PGD 2受体1（PTGDR）。此外，我们发现，一个转基因小鼠，K14-Ptgs 2，其靶向皮肤的前列腺素-内过氧化物合酶2的表达，表现出皮肤中的PGD 2水平升高，并发展脱发，毛囊小型化，和皮脂腺增生，这都是人类阿加的标志。这些结果将PGD 2定义为阿加中毛发生长的抑制剂，并表明PGD 2-GPR 44途径作为治疗的潜在靶点。
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.