title: Activation of cytoprotective prostaglandin synthase-1 by minoxidil as a possible explanation for its hair growth-stimulating effect.
abstract: Data from the literature indicate that nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, naproxen, piroxicam, or ibuprofen, induce hair loss in vivo. These NSAIDs are well-known inhibitors of both the cytoprotective isoform of prostaglandin endoperoxide synthase-1 (PGHS-1) and of the inducible form (PGHS-2). By immunohistochemical staining, we found that PGHS-1 is the main isoform present in the dermal papilla from normal human hair follicle (either anagen or catagen), whereas PGHS-2 was only faintly and exclusively expressed in anagen dermal papilla. Thus, PGHS-1 might be the primary target of the hair growth-inhibitory effects of NSAIDs. We thus speculated that activation of PGHS-1 might be a mechanism by which minoxidil (2,4-diamino-6-piperidinopyrimidine-3-oxyde) stimulates hair growth in vivo. We demonstrate here that minoxidil is a potent activator of purified PGHS-1 (AC50 = 80 microM), as assayed by oxygen consumption and PGE2 production. This activation was also evidenced by increased PGE2 production by BALB/c 3T3 fibroblasts and by human dermal papilla fibroblasts in culture. Our findings suggest that minoxidil and its derivatives may have a cytoprotective activity in vivo and that more potent second-generation hair growth-promoting drugs might be designed, based on this mechanism.
authors.affiliation: Hair Biology Research Group, L'OREAL, Clichy, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Michelet
authors.forename: S
authors.initials: S
authors.lastname: Commo
authors.forename: N
authors.initials: N
authors.lastname: Billoni
authors.forename: Y F
authors.initials: YF
authors.lastname: Mahé
authors.forename: B A
authors.initials: BA
authors.lastname: Bernard
mesh_terms: D016475:3T3 Cells / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D018859:Hair Follicle / Q000166:cytology / Q000201:enzymology / Q000254:growth & development*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008914:Minoxidil / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D008914:Minoxidil; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone