Testosterone metabolism in human skin cells in vitro and its interaction with estradiol and dutasteride.
Since the limited knowledge of cutaneous drug metabolism can impair the development of specifically acting topical dermatics and transdermal application systems, the cell-type-specific androgen metabolism in human skin and its inhibition by drugs were investigated. Cultured human foreskin and scalp skin keratinocytes and fibroblasts as well as occipital scalp dermal papilla cells (DPC) were incubated with testosterone 10(-6) and 10(-8)M alone and in the presence of 17alpha-estradiol, 17beta-estradiol or dutasteride for 24 h. Androgens extracted from culture supernatants were subjected to thin-layer chromatography and quantified by beta-counting. In keratinocytes and DPC, dihydrotestosterone (DHT) was only formed to a low extent while androstenedione was the main metabolite. In fibroblasts, DHT formation was pronounced following 10(-8)M testosterone. Dutasteride 10(-8)M completely suppressed 5alpha-dihydro metabolite formation. 17alpha-Estradiol and 17beta-estradiol at nontoxic concentrations decreased 17-ketometabolites. Human skin regulates testosterone action by cell-type-specific activation or deactivation. Effects of 17alpha-estradiol in androgenetic alopecia are not due to 5alpha-reductase inhibition. Dutasteride may be useful in acne and androgenetic alopecia.
Münster
U
U
Abteilung für Pharmakologie und Toxikologie, Institut für Pharmazie, Freie Universität Berlin, Berlin, Deutschland.
Hammer
S
S
Blume-Peytavi
U
U
Schäfer-Korting
M
M
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000096:biosynthesis; D000726:Androgen Antagonists / Q000494:pharmacology*; D001378:Azasteroids / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002855:Chromatography, Thin Layer; D013196:Dihydrotestosterone / Q000494:pharmacology; D000068538:Dutasteride; D004958:Estradiol / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*
D000726:Androgen Antagonists; D001378:Azasteroids; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D000068538:Dutasteride