072 17alpha-Estradiol Induces Aromatase Activity in Isolated Human Hair Follicles.

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

Women tend to develop AGA later and milder than men, but with the decline of serum estrogens during the menopause many women show an accelerated progression of AGA. Estrogens may play a protective role against the development of AGA, because pregnant women are in some way protected form androgenetic hair loss, but lose their hairs again postpartum. In Europe, topically applied estrogens such as 17ß-estadiole are used to treat androgenetic alopecia, both in women and men. The femal hormone 17ß- Estradiol can be used only in women, whereas the hormonally almost inactive isomer 17a-estradiol can be used in men as well. Although some clinical studies show considerable success of such an approach, the underlying pathways of 17a-estradiol-induced hair regrowth are unknown. It is likely not a receptor mediated hormon effect, since 17ß-Estradiol is an hormon and 17a-estradiol not. Recently it has been shown that hair follicles from women with AGA express more aromatase activity compared to male hair follices, and interestingly those women taking aromatase inhibitors tend to develop rapidly progressive AGA. These circumstantial lines of evidence indicate a role of aromatase during the pathogenesis of AGA. In order to unravel the pathways of 17a-estradiol-mediated effcets on the hair follicles, we measured aromatase activity in isolated intact human occipital hair follicles by incubating hair follicles with H3-1ßandrostenedione with or without 17a-estradiol (1nM, 100nM, 1µM) for 24 or 48 hours. In comparison to the controls (female, 444fmol/mm3 = 100%), we noticed a concentration- and time-dependent increase of aromatase activity in 17a-estradiol-incubated female hair follicles (e.g. 24h: 1nM = + 18%, 100nM = + 25%, 1µM =+ 57%; 24h: 1nM = +18%, 48h: 1nM = +25%). Our ex vivo results suggest that under the influence of 17a-estradiol an increased conversion of testosterone to 17ß-estradiol and androstendione to estrone takes place. In theory this pathway may diminish the amount of intrafollicular testosterone available for conversion to DHT, and because DHT is the major mediator of AGA, this pathway may explain the beneficial effect of 17a-estradiol on the development and progression of AGA.esults suggest that SRY is a male-specific transcriptional stimulator for 5aRII in hDPCs.