Modulation of androgen receptor transcriptional activity by anti-acne reagents.

Background: To study the potential anti-androgenic activity of roxithromycin (RXM), we previously used human dermal fibroblasts transiently transfected with the expression vector of androgen receptor (AR) coactivator ARA55 as the in vitro model reflecting the end-organ hypersensitivity.

Objective: To examine the potential anti-androgenic activity of anti-acne therapeutic agents, nadifloxacin (NDFX), RXM, all-trans retinoic acid (atRA), and glycolic acid (GA), we carried out the transient transfection assays using the CV-1 cells as a more sensitive assay system.

Results: The result showed that 5 microg/ml of RXM suppress 10(-9)M R1881-induced AR transcriptional activity by 21.2%. 50 microg/ml of NDFX can suppress AR transcriptional activity to 29.8%. Furthermore, the assays with treatment of 1, 5, 10, or 50 microg/ml NDFX in the presence of 1 microg/ml RXM showed that 5, 10, or 50 microg/ml NDFX inhibits the AR transactivity by 32.7, 31.1 or 61.0%, respectively, indicating the synergistic effect of NDFX and RXM. Besides 10(-5)M atRA suppressed the R1881-induced luciferase activity by 50%, but GA did not alter AR transactivity.

Conclusions: We demonstrated that anti-acne agents available in the clinical practice can exert anti-androgenic effects in the treatment of acne.