Catherine Gerst

Type-1 steroid 5α-reductase is functionally active in the hair follicle as evidenced by new selective inhibitors of either type-1 or type-2 human steroid 5α-reductase

Abstract: Steroid 5α‐reductase catalyzes the reduction of testosterone (T) into the very potent androgen dihydrotestosterone (DHT). The different tissue expression patterns of the two isoforms of 5α‐reductase, namely type‐1 and type‐2 5α‐reductase (5α‐R1 and 5α‐R2, respectively), have prompted studies directed towards the synthesis of selective 5α‐R1 or 5α‐R2 inhibitors. In this present work, we have performed a structure/activity study on the inhibitory potential of indole carboxylic acids against hair follicle 5α‐reductase activity. We have demonstrated that this class of molecules were potent inhibitors of either 5α‐R1 or 5α‐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 5α‐R1 or 5α‐R1/R2 inhibitors were able to inhibit 5α‐reductase activity in plucked hairs from female volunteers or in freshly isolated female hair follicles, selective 5α‐R2 inhibitors being inactive.