Lack of Significant Estrogenic or Antiestrogenic Activity of Pyrethroid Insecticides in Three in Vitro Assays Based on Classic Estrogen Receptor alpha-Mediated Mechanisms | Zendy

Koichi Saito | Zendy

Open Access

Lack of Significant Estrogenic or Antiestrogenic Activity of Pyrethroid Insecticides in Three in Vitro Assays Based on Classic Estrogen Receptor alpha-Mediated Mechanisms

Author(s) -

Koichi Saito

Publication year - 2000

Publication title -

toxicological sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.352

H-Index - 183

eISSN - 1096-6080

pISSN - 1096-0929

DOI - 10.1093/toxsci/57.1.54

Subject(s) - transactivation , reporter gene , estrogen receptor , luciferase , estrogen receptor alpha , pyrethroid , phytoestrogens , in vitro , biology , cypermethrin , chemistry , antiestrogen , estrogen , pharmacology , endocrinology , biochemistry , transcription factor , gene expression , transfection , gene , genetics , cancer , pesticide , breast cancer , agronomy

Estrogenic and antiestrogenic activity of pyrethroid insecticides (d-trans-allethrin, cypermethrin, empenthrin, fenvalerate, imiprothrin, permethrin, d-phenothrin and prallethrin) was evaluated using a suite of three in vitro assays based on classic human estrogen receptor alpha (hER alpha)-mediated mechanisms. A mammalian cell-based luciferase reporter gene assay was developed for examining effects on hER alpha-mediated gene activation. hER alpha-independent effects on the gene activation were examined using control cells with constitutive luciferase activation by a herpes simplex virus thymidine kinase (HSV-TK) promoter for determining appropriate dose levels of test chemicals. Moreover, the test chemical-dependent interaction between hER alpha and a coactivator (transcriptional intermediary factor 2: TIF2) was analyzed by a yeast two-hybrid method, competitive binding to hER alpha being assayed by a fluorescence polarization method. Significant (p < 0.05) positive effects of estrogenic substances (E2/estradiol, diethylstilbestrol, and p-nonylphenol) were detected in all assays. An antiestrogen, 4-hydroxytamoxifen, significantly inhibited E2-mediated transactivation and interaction between hER alpha and TIF2 through hER alpha binding (p < 0.05). However, none of the pyrethroids tested showed significant (p < 0.05) estrogenic or antiestrogenic effects (100 nM-10 microM), indicating that they do not impact on the classic hER alpha-mediated activation pathway in vitro.

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