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
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초록

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. Copyright © 2024. Published by Elsevier Inc.

키워드

Endocrine disruptionEstrogen receptor αFenvalerateInsecticideLipid accumulationIN-VITROPYRETHROID INSECTICIDESANTIESTROGENIC ACTIVITYPROMOTE ADIPOGENESISREPORTERALPHAEXPOSUREPESTICIDESTOXICITYOBESITY
제목
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
저자
Jeong, Da-HyunJung, Da-WoonLee, Hee-Seok
DOI
10.1016/j.cbpc.2024.109955
발행일
2024-09
유형
Article
저널명
Comparative Biochemistry and Physiology, Part C
283