PMID- 14528059 OWN - NLM STAT- MEDLINE DCOM- 20040210 LR - 20171101 IS - 1422-2868 (Print) IS - 1422-2868 (Linking) VI - 16 IP - 6 DP - 2003 Nov-Dec TI - Testosterone metabolism in human skin cells in vitro and its interaction with estradiol and dutasteride. PG - 356-66 AB - 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. CI - Copyright 2003 S. Karger AG, Basel FAU - Munster, U AU - Munster U AD - Abteilung fur Pharmakologie und Toxikologie, Institut fur Pharmazie, Freie Universitat Berlin, Berlin, Deutschland. FAU - Hammer, S AU - Hammer S FAU - Blume-Peytavi, U AU - Blume-Peytavi U FAU - Schafer-Korting, M AU - Schafer-Korting M LA - eng PT - Journal Article PL - Switzerland TA - Skin Pharmacol Appl Skin Physiol JT - Skin pharmacology and applied skin physiology JID - 9807277 RN - 0 (Androgen Antagonists) RN - 0 (Azasteroids) RN - 08J2K08A3Y (Dihydrotestosterone) RN - 3XMK78S47O (Testosterone) RN - 4TI98Z838E (Estradiol) RN - EC 1.3.99.5 (3-Oxo-5-alpha-Steroid 4-Dehydrogenase) RN - O0J6XJN02I (Dutasteride) SB - IM MH - 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/biosynthesis MH - Androgen Antagonists/*pharmacology MH - Azasteroids/*pharmacology MH - Binding, Competitive/drug effects MH - Cell Survival/drug effects MH - Chromatography, Thin Layer MH - Dihydrotestosterone/pharmacology MH - Dutasteride MH - Estradiol/*pharmacology MH - Fibroblasts/drug effects/metabolism MH - Humans MH - Keratinocytes/drug effects/metabolism MH - Male MH - Reverse Transcriptase Polymerase Chain Reaction MH - Skin/cytology/enzymology/*metabolism MH - Testosterone/*metabolism EDAT- 2003/10/07 05:00 MHDA- 2004/02/11 05:00 CRDT- 2003/10/07 05:00 PHST- 2002/07/26 00:00 [received] PHST- 2003/10/07 05:00 [pubmed] PHST- 2004/02/11 05:00 [medline] PHST- 2003/10/07 05:00 [entrez] AID - 72930 [pii] AID - 10.1159/000072930 [doi] PST - ppublish SO - Skin Pharmacol Appl Skin Physiol. 2003 Nov-Dec;16(6):356-66. doi: 10.1159/000072930.