Maria Dalko

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.

6-O glucose linoleate supports in vitro human hair growth and lipid synthesis

The hair follicle is a very active organ with a complex structure, which produces a hair fibre at a rate of 0.3 mm a day. Accordingly, the hair follicle is highly demanding in energy source, as the hair bulb matrix cells are endowed with one of the highest rates of proliferation in the human body. Moreover, recent data have shown the involvement of lipids in hair follicle function. As in vitro‐grown hair follicle keeps producing a hair fibre that closely resembles the natural hair fibre, we decided to use this model to investigate the role of a new of glucose linoleate derivative (6‐O‐linoleyl‐d‐glucose: 6‐O‐GL) as a lipid precursor and energy provider. Our results demonstrated that 6‐O‐GL was (i) quite stable and surprisingly resistant to oxidative degradation, and (ii) readily taken up and metabolized by the hair follicle into various lipids, namely neutral lipids, ceramides and polar lipids. Moreover, it supported hair follicle growth and survival in a glucose‐ and linoleic‐acid free medium. 6‐O‐GL thus appeared to be a bi‐functional nutrient, ensuring both proper fibre quality and production by the hair follicle.