Effect of 5alpha-dihydrotestosterone and testosterone on apoptosis in human dermal papilla cells.
Pathogenetic mechanisms in androgenetic alopecia are not yet fully understood; however, it is commonly accepted that androgens like testosterone (T) and 5alpha-dihydrotestosterone (5alpha-DHT) inhibit hair follicle activity with early induction of the catagen. Thus, we investigated the influence of T and 5alpha-DHT on proliferation, cell death and bcl-2/bax expression in cultured dermal papilla cells (DPC) from nonbalding scalp regions of healthy volunteers. T and 5alpha-DHT induced apoptosis in DPC in a dose-dependent and time-related manner; in addition a necrotic effect due to T at 10(-5) M was found. Interestingly, bcl-2 protein expression was decreased in T- and 5alpha-DHT-treated cells, leading to an increase in the bax/bcl-2 ratio. In addition, T and 5alpha-DHT induced proteolytic cleavage of caspase 8 and inhibited proliferation of DPC at 10(-5) M. High concentrations of T and 5alpha-DHT were needed to induce apoptotic effects in DPC. These data suggest that DPC from nonbalding scalp regions do have the capacity to undergo apoptosis, but need a high androgen stimulus. The present study provides an interesting new pathogenetic approach in androgenetic alopecia.
Winiarska
A
A
Department of Dermatology and Allergy, Charité-Universitatsmedizin Berlin, Berlin, Germany.
Mandt
N
N
Kamp
H
H
Hossini
A
A
Seltmann
H
H
Zouboulis
C C
CC
Blume-Peytavi
U
U
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology*; D019254:Genes, bcl-2 / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D009336:Necrosis; D012313:RNA / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000187:drug effects*; D013739:Testosterone / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein / Q000502:physiology
D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; D013196:Dihydrotestosterone; D013739:Testosterone; D012313:RNA; D053148:Caspase 3; D053181:Caspase 8; C022616:thiazolyl blue