O#27   Aromatase and oxidative 3a-hydroxysteroid dehydrogenases are present in human hair follicles and regulate intrafollicular DHT levels

Rolf Hoffmann. Dept of Dermatology, Philipp University, Marburg, Germany

Dihydrotestosterone (DHT) is the most important trigger of androgen-dependent hair growth. The intrafollicular concentration of DHT is mainly regulated by steroid 5a-reductase. However, recent data from other tissues revealed that DHT levels can also be modulated via the action of aromatase or oxidative 3a-hydroxysteroid dehydrogenases (3HSD). We therefore addressed the questions whether aromatase and 3HSD are present in human hair follicles and whether their enzymatic activity can be modulated. By the use of immunohistochemistry, quantitative analysis of steroids with HPLC and direct measurement of enzyme activity, we were able to detect aromatase mainly in the epithelial parts of the hair follicle, whereas 3HSD was mainly expressed in the dermal papilla. In addition, were able to show that aromatase activity in isolated intact human hair follicles is modulated by 17b-estradiol in such way that in comparison to the controls, we noticed a concentration- and time-dependent increase of aromatase activity in 17b-estradiol-incubated female hair follicles (e.g. 24h: 1nM = + 18%, 100nM = + 25%, 1µM = + 57%; 24h: 1nM = +18%, 48h: 1nM = +25%). Moreover, we noticed that the dermal papilla is able to convert the weak androgen 3a-Androstenediol back to DHT via 3HSD. In summary, our ex vivo results suggest that aromatase and 3HSD are present in the hair follicle and act antagonistically. In theory the aromatase pathway may diminish the amount of intrafollicular testosterone available for conversion to DHT, whereas 3HSD adds additional DHT. Our results suggest that increasing aromatase or inhibiting 3HSD activity are novel approaches to stop the development or progression of DHT-mediated processes of hair growth such as androgenetic alopecia.