We previously described the effects and behaviour of the main circulating active androgen testosterone (Testo) and its main active intracellular metabolite DHT in an androgen sensitive sebocytes (abstract X, SID, 2019). Testo and DHT readily induce 1) androgen receptor (AR) translocation, 2) expression of target genes and then 3) a lipogenic differentiation program. DHEA is not significantly transformed into Testo, had no significant androgenic (agonist), nor anti-androgenic (antagonist) effect by itself in the tested conditions.
Here we analysed the activity of reference anti-androgens (Finasteride, Dutasteride, Cyproterone acetate), at the level of their potential targets (5-alpha-reductase, AR translocation, induced transcripts) and in a functional lipid accumulation assay. We also evaluated this androgen-induced lipid accumulation assay as a potential pharmacological tool to detect potential inhibitors from both androgenic and non-androgenic origins.

The androgen sensitive sebocytes should allow to characterize both the activity and the mechanism of action of anti-androgen drugs. These anti-androgens may act at the level of androgen metabolism, AR translocation, AR nuclear activity and thus may have (or not) a functional effect on androgen-induced lipogenic differentiation of these cells. If we focus on these functional effects, other (non-androgenic) potential cell metabolism modulators may also work.

[¹⁴C]-Testo metabolism was analysed after incubation with cell cultures at different times and extraction, chromatography/phosphorimaging². RASD1 expression was measured by RT-qPCR¹.
AR translocation was followed by immunofluorescence1. Lipid accumulation was evidenced by incubation with the fluorescent probe Bodipy^®1. Automated photography and image analysis was performed using an INCell Analyzer^TM 2200 (GE Healthcare). The tested compounds are listed in fig 3.