Acute atrazine exposure does not impair 5α-reductase activity in hepatic and blood-brain barrier cells

Atrazine is a widely used herbicide with non-canonical endocrine-disrupting activity as it does not act as a hormone agonist yet it induces hormone imbalances, represented by induced feminization and heightened aromatase levels. Still, its endocrinological effects remain poorly understood especially in mammalian systems. This study investigated whether atrazine and its two major metabolites (deisopropylatrazine and deethylatrazine) interfere with the conversion of testosterone to dihydrotestosterone in vitro in two cellular models representing the liver and the blood-brain barrier, the latter being herein reported for the first time. Transcriptional activation of the estrogen receptor was assessed, while potential interactions with steroid 5α-reductase isoforms type I and II were evaluated by molecular docking. Testosterone conversion to dihydrotestosterone was measured in Hep-G2 and bEnd.3 cells after acute exposure to atrazine and its two main metabolites at different concentrations (100nM - 50μM), along with endpoint cellular metabolic activity. Neither atrazine nor its metabolites activated the estrogen receptor and molecular docking predicted weak interactions of atrazine, deisopropylatrazine and deethylatrazine, with both 5α-reductase isoforms compared with testosterone. Consistent with these predictions, no significant decreases in dihydrotestosterone synthesis were observed in either cell line following treatment, both Hep-G2 and bEnd.3 cells lines retaining the unaffected ability of converting testosterone to its more potent form - dihydrotestosterone. These results indicate that atrazine and its major metabolites do not directly impair testosterone conversion to dihydrotestosterone, and that they are unlikely to disrupt androgen conversion through inhibition of 5α-reductase activity, the main anti-androgenic mechanism known to cause heightened aromatase levels.