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.

Prostaglandin metabolism in human hair follicle

“…Interestingly, mPGES-1 expression in DP was reminiscent of the previously described specific DP COX-1 expression (13). mPGES-1 expression in DP was somewhat unexpected as it was generally coupled to that of COX-2, which was previously found absent in DP (13). One thus has to admit that mPGES-1 expression in hair follicle DP is coupled to COX-1 rather than to COX-2 expression, as recently observed in murine mammary gland (31).…”

“…Immunological approach nevertheless revealed that mPGES-1 was strongly expressed in DP, a compartment which was usually absent in plucked hair follicles and whose contribution could not be evaluated in RT-PCR studies. Interestingly, mPGES-1 expression in DP was reminiscent of the previously described specific DP COX-1 expression (13). mPGES-1 expression in DP was somewhat unexpected as it was generally coupled to that of COX-2, which was previously found absent in DP (13).…”

“…Indeed, topical use of viprostol, a PGE 2 analogue, was reported to increase human hair growth and terminal hair counts after 50 weeks treatment (11) while administration of 16,16-dimethyl PGE 2 protected mice from radiation-induced alopecia (12). Minoxidil, a potent trichogenic agent, was found to enhance prostaglandin endoperoxide synthase-1 (PGHS-1) activity, suggesting a link between prostaglandin synthesis and hair growth (13), as later confirmed by the role of PGHS-2 in the control of hair cycle (14). Latanoprost, a PGF 2a analogue used to treat glaucoma, was reported to induce hypertrichosis in humans (15) and stump-tailed macaque (16).…”

Wound Healing Involves Induction of Cyclooxygenase-2 Expression in Rat Skin

“…In normal human skin, Müller-Decker et al (1999) reported the COX-2 protein expression in individual keratinocytes of the epidermis and hair follicles. However, according to Michelet et al (1997), COX-1 immunostaining was observed in the dermal papilla from human hair follicles, whereas COX-2 in the dermal papilla was expressed only in the anagen phase of the hair cycle. Although their findings appear to differ from ours, they actually might have observed expression in endothelial cells and fibroblast-like cells within the dermal papilla.…”

Topical Diclofenac 3% Gel for Actinic Keratosis May Induce Terminal Hair in Male Androgenetic Alopecia: A Report of Three Cases

“…Minoxidil, a reference treatment to stimulate hair regrowth, increases PGE 2 . Bimatoprost and latanoprost, PGF 2 α analogs, are recently used successfully to increase the length of eyelashes (6,8).…”