P46 INFLUENCE OF ESTROGENS ON THE ANDROGEN METABOLISM IN DIFFERENT SUBUNITS OF HUMAN HAIR FOLLICLES

Niiyama S., Hoffmann R. Dept. of Dermatology, Philipp University, Marburg, Germany.

Androgenetic alopecia (AGA) can be defined as a dihydrotestosterone (DHT)-mediated process which results in progressive miniaturization of DHT-sensitive hair follicles (HF). DHT is supplied via the dermal papilla (DP), which is able to convert circulating testosterone (T) to DHT through type 2 5a-reductase (5a-R). Current systemic treatments involve either the use of antiandrogens, such as cyproterone acetate, or enzyme inhibitors such as finasteride (F). Solutions containing either estradiol benzoate, estradiol valerate, 17a- or 17a-estradiol (17a-E, 17a-E) are commercially available in Europe and have been shown to be capable of treating AGA. However, the molecular pathways involved in estrogen-mediated induction of hair growth in AGA are unknown. Some authors found that E inhibited 5a-R activity and therefore we addressed the question whether 17a- or 17a-E are able to modulate 5aR, 3a-hydroxysteroid dehydrogenase (3a-HSD) or 17a-hydroxysteroid dehydrogenase (17a-HSD) activity in isolated compartments of the human HF. For this purpose, scalp biopsies from 9 healthy volunteers were taken and from each biopsy 3 root sheaths (RS), 3 connective tissue sheaths (CTS) and 6 dermal papillae were dissected and incubated in the presence of 3aH-T and either 17a-E, 17a-E, progesterone or F (at 1mM, 100nM or 1nM) for up to 48 hours. Thereafter HPLC analysis of culture supernatants was performed to detect T-metabolites and our results showed that at the tested concentrations F was a superior inhibitor of DHT formation. Even 1nM F inhibited DHT synthesis in DP by 86% and 1nM progesterone by 75%. Higher concentrations of F resulted in complete inhibition. Estrogens were less able to inhibit the synthesis of DHT in DP (e.g. 100nM 17a-E: 20%; 100nM 17a-E: 60%). Whether E directly inhibit 5aR in DP4s or whether the effect of estrogens might be explained by an increased conversion of T to the weaker androgens A-dione (via 17a-HSD), A-diol (via 3a-HSD) or 17a-E (via aromatase) thereby diminishing the amount of T available for the conversion to DHT remains to be shown. Furthermore, it is unclear whether E may have an effect on 5aR at higher concentrations.