Type-1 steroid 5 alpha-reductase is functionally active in the hair follicle as evidenced by new selective inhibitors of either type-1 or type-2 human steroid 5 alpha-reductase.
Steroid 5 alpha-reductase catalyzes the reduction of testosterone (T) into the very potent androgen dihydrotestosterone (DHT). The different tissue expression patterns of the two isoforms of 5 alpha-reductase, namely type-1 and type-2 5 alpha-reductase (5 alpha-R1 and 5 alpha-R2, respectively), have prompted studies directed towards the synthesis of selective 5 alpha-R1 or 5 alpha-R2 inhibitors. In this present work, we have performed a structure/activity study on the inhibitory potential of indole carboxylic acids against hair follicle 5 alpha-reductase activity. We have demonstrated that this class of molecules were potent inhibitors of either 5 alpha-R1 or 5 alpha-R2 or both depending on (i) substituents in positions 4, 5 or 6 and (ii) the presence of a free carboxylic group. We have also found that only 5 alpha-R1 or 5 alpha-R1/R2 inhibitors were able to inhibit 5 alpha-reductase activity in plucked hairs from female volunteers or in freshly isolated female hair follicles, selective 5 alpha-R2 inhibitors being inactive.
Gerst
C
C
L'Oréal Recherche Avancée, Hair Biology Group, Centre Recherche C. Zviak, Clichy, France.
Dalko
M
M
Pichaud
P
P
Galey
J B
JB
Buan
B
B
Bernard
B A
BA
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors; D000818:Animals; D019556:COS Cells; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology; D004210:Dissection; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018859:Hair Follicle / Q000201:enzymology*; D000882:Haplorhini; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase