ACTIVATION OF CYTOPROTECTIVE PROSTAGLANDIN SYNTHASE-1 BY MINOXIDIL ASA POSSIBLE EXPLANATION FOR ITS HAIR GROWTH-STIMULATING EFFECT

Data from the literature indicate that nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, naproxen, piroxicam, or ibuprofe n, induce hair loss ill vivo., These NSAIDs are well-known inhibitors of both the cytoprotective isoform of prostaglandin endoperoxide synth ase-l (PGHS-1) and of the inducible form (PGHS-2), By immunohistochemi cal staining, we found that PGHS-1 is the main isoform present in the dermal papilla from normal human hair follicle (either anagen or catag en), whereas PGHS-2 was only faintly and exclusively expressed in anag en dermal papilla, Thus, PGHS-1 might be the primary target of the hai r growth-inhibitory effects of NSAIDs, We thus speculated that activat ion of PGHS-1 might be a mechanism by which minoxidil (2,4-diamino-6-p iperidinopyrimidine-3-oxyde) stimulates hair growth in vivo. We demons trate here that minoxidil is a potent activator of purified PGHS-1 (AC 50 = 80 mu M), as assayed by oxygen consumption and PGE(2) production, This activation was also evidenced by increased PGE(2) production by BALB/c 3T3 fibroblasts and by human dermal papilla fibroblasts in cult ure. Our findings suggest that minoxidil and its derivatives may have a cytoprotective activity in vivo and that more potent second-generati on hair growth-promoting drugs might be designed, based on this mechan ism.