Potential anti-androgenic activity of roxithromycin in skin.
Since acne formation is a multistep process accelerated by androgens, we examined whether a new anti-acne antibiotic roxithromycin (RXM) may act as anti-androgen using transient transfection assays in human skin fibroblasts. The result showed no significant effect of 0.5, 1 and 5 microg/ml RXM on 10(-9) M R1881-induced androgen receptor (AR) transcriptional activity. While the cotransfection of exogenous ARA55, a novel AR coactivator, increased AR transactivation up to 2.59-fold, this increase was attenuated by 5 microg/ml RXM to 64.7%. Semiquantitative RT-PCR results showed that 0.1 mM H(2)O(2) treatment increased ARA55 mRNA expression level, indicating that reactive oxygen species increase the expression of ARA55 in skin. These results suggest that RXM may serve as anti-androgen only in the hypersensitive state to androgen, but not in the physiological state, through modulating end-organ hypersensitive condition to androgen possibly involving the pathway from reactive oxygen species to ARA55.
Inui
S
S
Department of Dermatology, Course of Molecular Medicine, Graduate School of Medicine, Osaka University, Osaka, 2-2, C5, Yamada-oka, Suita-shi, Osaka 565-0871, Japan. inui@derma.med.osaka-u.ac.jp
Nakajima
T
T
Fukuzato
Y
Y
Fujimoto
N
N
Chang
C
C
Yoshikawa
K
K
Itami
S
S
D000726:Androgen Antagonists; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D015741:Metribolone / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015575:Roxithromycin / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
D000726:Androgen Antagonists; D015575:Roxithromycin; D015741:Metribolone; D008156:Luciferases