title: Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.
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 PGD(2) as an inhibitor of hair growth in AGA and suggest the PGD(2)-GPR44 pathway as a potential target for treatment.
authors.affiliation: Department of Dermatology, Kligman Laboratories, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Garza
authors.forename: Yaping
authors.initials: Y
authors.lastname: Liu
authors.forename: Zaixin
authors.initials: Z
authors.lastname: Yang
authors.forename: Brinda
authors.initials: B
authors.lastname: Alagesan
authors.forename: John A
authors.initials: JA
authors.lastname: Lawson
authors.forename: Scott M
authors.initials: SM
authors.lastname: Norberg
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Loy
authors.forename: Tailun
authors.initials: T
authors.lastname: Zhao
authors.forename: Hanz B
authors.initials: HB
authors.lastname: Blatt
authors.forename: David C
authors.initials: DC
authors.lastname: Stanton
authors.forename: Lee
authors.initials: L
authors.lastname: Carrasco
authors.forename: Gurpreet
authors.initials: G
authors.lastname: Ahluwalia
authors.forename: Susan M
authors.initials: SM
authors.lastname: Fischer
authors.forename: Garret A
authors.initials: GA
authors.lastname: FitzGerald
authors.forename: George
authors.initials: G
authors.lastname: Cotsarelis
mesh_terms: D000505:Alopecia / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology; D005260:Female; D020869:Gene Expression Profiling; D006197:Hair / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development*; D018859:Hair Follicle / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D012535:Scalp / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
chemical_list: C477819:15-deoxyprostaglandin J2; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D011451:Prostaglandin-Endoperoxide Synthases; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor