Influence of estrogens on the androgen metabolism in different subunits of human hair follicles.

The molecular pathways involved in estrogen-mediated induction of hair growth in androgenetic alopecia are unknown. Some authors found that estradiol (E) inhibited 5alpha-reductase (5alpha-R) activity and therefore we addressed the question whether 17alpha- or 17beta-E are able to modulate the activity of 5alpha-R, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) or 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in isolated compartments of human hair follicles. For this purpose, scalp biopsies from volunteers were taken and from each biopsy root sheaths, connective tissue sheaths and dermal papillae (DP) were dissected and incubated in the presence of 3H-testosterone (T) and, in addition, either 17alpha-E, 17beta-E, progesterone or finasteride for up to 48 hrs. Thereafter high-performance liquid chromatography analysis of culture supernatants was performed to detect T-metabolites. At the tested concentrations, finasteride was found to be a major inhibitor of dihydrotestosterone (DHT) formation. Even 1 nM finasteride inhibited DHT synthesis in DP by 86% and 1 nM progesterone by 75%. Estrogens were less able to inhibit the synthesis of DHT in DP (e.g. 100 nM 17alpha-E: 20%; 100 nM 17beta-E: 60%). Whether E directly inhibits 5alpha-R in DP's or whether the effect of estrogens might be explained by an increased conversion of T to the weaker androgens such as androstendione (via 17beta-HSD), androstenediol (via 3beta-HSD) or 17beta-E (via aromatase), thereby diminishing the amount of T available for the conversion to DHT, remains to be shown.