Activation of cytoprotective prostaglandin synthase-1 by minoxidil as a possible explanation for its hair growth-stimulating effect

J Invest Dermatol. 1997 Feb;108(2):205-9. doi: 10.1111/1523-1747.ep12334249.

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.

MeSH terms

  • 3T3 Cells / metabolism
  • Animals
  • Cell Survival / drug effects
  • Dinoprostone / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Hair Follicle / cytology
  • Hair Follicle / enzymology
  • Hair Follicle / growth & development*
  • Humans
  • Isoenzymes / metabolism*
  • Mice
  • Minoxidil / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / metabolism*

Substances

  • Isoenzymes
  • Minoxidil
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone