Confirmation of the steroid hormone receptor-mediated endocrine disrupting potential of fenvalerate following the Organization for Economic Cooperation and Development test guidelines, and its estrogen receptor α-dependent effects on lipid accumulation

In this study, we focused on confirming the steroid hormone receptor-mediated endocrine-disrupting potential of the pyrethroid insecticide fenvalerate and unraveling the underlying mechanisms. Therefore, we assessed estrogen receptor-α (ERα)- and androgen receptor (AR)-mediated responses in vitro using a hormone response element-dependent transcription activation assay with a luciferase reporter following the Organization for Economic Cooperation and Development (OECD) test guidelines. We observed that fenvalerate acted as estrogen by inducing the translocation of cytosolic ERα to the nucleus via ERα dimerization, whereas it exhibited no AR-mediated androgen response element-dependent luciferase activity. Furthermore, we confirmed that fenvalerate-induced activation of ERα caused lipid accumulation, promoted in a fenvalerate-dependent manner in 3 T3-L1 adipocytes. Moreover, fenvalerate-induced lipid accumulation was inhibited in the presence of an ERα-selective antagonist, whereas it remained unaffected in the presence of a glucocorticoid receptor (GR)-specific inhibitor. In addition, fenvalerate was found to stimulate the expression of transcription factors that promote lipid accumulation in 3 T1-L1 adipocytes, and co-treatment with an ERα-selective antagonist suppressed adipogenic/ lipogenic transcription factors at both mRNA and protein levels. These findings suggest that fenvalerate exposure may lead to lipid accumulation by interfering with ERα activation-dependent processes, thus causing an ERα-mediated endocrine-disrupting effect. [Display omitted] • This study pointed out SHR-mediated endocrine disruption by fenvalerate. • Fenvalerate induced ERα-mediated endocrine disruption via a direct binding to ERα. • Fenvalerate did not induce on AR- and GR-mediated transcriptional activation activity. • Fenvalerate up-regulated the transcription level of lipid metabolism-related factors. • These adverse effect were by interfering with ERα activation-dependent processes. [ABSTRACT FROM AUTHOR]