17alpha-estradiol induces aromatase activity in intact human anagen hair follicles ex vivo.
For topical treatment of androgenetic alopecia (AGA) in women, solutions containing either estradiol benzoate, estradiol valerate, 17beta- or 17alpha-estradiol are commercially available in Europe and some studies show an increased anagen and decreased telogen rate after treatment as compared with placebo. At present it is not precisely known how estrogens mediate their beneficial effect on AGA-affected hair follicles. We have shown recently that 17alpha-estradiol is able to diminish the amount of dihydrotestosterone (DHT) formed by human hair follicles after incubation with testosterone, while increasing the concentration of weaker steroids such as estrogens. Because aromatase is involved in the conversion of testosterone to estrogens and because there is some clinical evidence that aromatase activity may be involved in the pathogenesis of AGA, we addressed the question whether aromatase is expressed in human hair follicles and whether 17alpha-estradiol is able to modify the aromatase activity. Herewith we were able to demonstrate that intact, microdissected hair follicles from female donors express considerably more aromatase activity than hair follicles from male donors. Using immunohistochemistry, we detected the aromatase mainly in the epithelial parts of the hair follicle and not in the dermal papilla. Furthermore, we show that in comparison to the controls, we noticed in 17alpha-estradiol-incubated (1 nM) female hair follicles a concentration- and time-dependent increase of aromatase activity (at 24 h: 1 nM = +18%, 100 nM = +25%, 1 micro M = +57%; 24 h: 1 nM = +18%, 48 h: 1 nM = +25%). In conclusion, our ex vivo experiments suggest that under the influence of 17alpha-estradiol an increased conversion of testosterone to 17beta-estradiol and androstendione to estrone takes place, which might explain the beneficial effects of estrogen treatment of AGA.
Hoffmann
R
R
Department of Dermatology, Philipp University, Deutschhausstrasse 9, D-35033 Marburg, Germany.
Niiyama
S
S
Huth
A
A
Kissling
S
S
Happle
R
R
D000328:Adult; D000505:Alopecia / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D000735:Androstenedione / Q000378:metabolism; D001141:Aromatase / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D004970:Estrone / Q000378:metabolism; D005260:Female; D018859:Hair Follicle / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D013739:Testosterone / Q000378:metabolism
D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D001141:Aromatase