Expression of NAD+ dependent 15-hydroxyprostaglandin dehydrogenase and protection of prostaglandins in human hair follicle.
NAD(+) dependent 15-hydroxyprostaglandin dehydrogenate (15-PGDH) catalyses oxidation of 15(S)-hydroxyl group of prostaglandins and as a result inactivates their physiological potential. Positive effects of prostaglandins or prostaglandin analogues were reported on terminal hair, vellus hair or eyelash growth and a complex prostaglandin network was recently described in human hair follicle. In the present study, we showed that 15-PGDH was expressed in human hair follicle mainly in melanocytes and keratinocytes, which brought us to consider this enzyme as a possible target to sustain local prostaglandin production. Using a recombinant enzymatic strategy, specific 15-PGDH inhibitors were screened. We identified a thiazolidine dione derivative exhibiting efficacy on follicular outer root sheath keratinocytes, since it concomitantly decreased the production of deactivated 13,14 dihydro 15-ketoprostaglandin F(2alpha) and sustained prostaglandin F(2alpha)in vitro production. In the context of recent interest in prostaglandins and prostaglandin analogues as hair regrowth agents, we postulated that the use of selected 15-PGDH inhibitors could reinforce or prolong the effect of these physiological mediators on hair and skin.
Michelet
Jean François
JF
Centre Charles Zviak, L'Oréal Recherche, Clichy, France. jfmichelet@rd.loreal.com
Colombe
Laurent
L
Gautier
Brigitte
B
Gaillard
Olivier
O
Benech
Florence
F
Pereira
Rui
R
Boulle
Christophe
C
Dalko-Csiba
Maria
M
Rozot
Roger
R
Neuwels
Michel
M
Bernard
Bruno Alain
BA
D001706:Biopsy; D015153:Blotting, Western; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D018859:Hair Follicle / Q000166:cytology* / Q000201:enzymology*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology; D008544:Melanocytes / Q000166:cytology / Q000201:enzymology; D008875:Middle Aged; D011453:Prostaglandins / Q000378:metabolism*
D004791:Enzyme Inhibitors; D011453:Prostaglandins; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; C031051:prostaglandin-F synthase