Prostaglandin D 2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia

Luis Garza, Yaping Liu, Zaixin Yang, Brinda Alagesan, John A. Lawson, Scott M. Norberg, Dorothy E. Loy, Tailun Zhao, Hanz B. Blatt, David C. Stanton, Lee Carrasco, Gurpreet Ahluwalia, Susan M. Fischer, Garret A. FitzGerald, George Cotsarelis

Research output: Contribution to journalArticle

Abstract

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 D 2 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 D 2 (PGD 2), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD 2 levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD 2 inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD 2 receptor G protein (heterotrimeric guanine nucleotide)-coupled receptor 44 (GPR44), but not the PGD 2 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 PGD 2 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 PGD 2-GPR44 pathway as a potential target for treatment.

Original languageEnglish (US)
Article number26ra34
JournalScience Translational Medicine
Volume4
Issue number126
DOIs
StatePublished - Mar 21 2012

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Prostaglandins D
Alopecia
Scalp
Hair
prostaglandin R2 D-isomerase
Growth
Guanine Nucleotides
Growth Disorders
Miniaturization
Heterotrimeric GTP-Binding Proteins
Prostaglandin D2
Sebaceous Glands
Growth Inhibitors
Skin
Hair Follicle
Prostaglandin-Endoperoxide Synthases
Transgenic Mice
Hyperplasia
Testosterone
Messenger RNA

ASJC Scopus subject areas

  • Medicine(all)

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Prostaglandin D 2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. / Garza, Luis; Liu, Yaping; Yang, Zaixin; Alagesan, Brinda; Lawson, John A.; Norberg, Scott M.; Loy, Dorothy E.; Zhao, Tailun; Blatt, Hanz B.; Stanton, David C.; Carrasco, Lee; Ahluwalia, Gurpreet; Fischer, Susan M.; FitzGerald, Garret A.; Cotsarelis, George.

In: Science Translational Medicine, Vol. 4, No. 126, 26ra34, 21.03.2012.

Research output: Contribution to journalArticle

Garza, L, 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 2012, 'Prostaglandin D 2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia', Science Translational Medicine, vol. 4, no. 126, 26ra34. https://doi.org/10.1126/scitranslmed.3003122
Garza, Luis ; Liu, Yaping ; Yang, Zaixin ; Alagesan, Brinda ; Lawson, John A. ; Norberg, Scott M. ; Loy, Dorothy E. ; Zhao, Tailun ; Blatt, Hanz B. ; Stanton, David C. ; Carrasco, Lee ; Ahluwalia, Gurpreet ; Fischer, Susan M. ; FitzGerald, Garret A. ; Cotsarelis, George. / Prostaglandin D 2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia. In: Science Translational Medicine. 2012 ; Vol. 4, No. 126.
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