Evaluation of in vitro methods for detecting the effects of various chemicals on the human progesterone receptor, with a focus on pyrethroid insecticides

• Published in: Toxicology letters Vol. 118; no. 3; pp. 147 - 155
• Main Authors: Sumida, Kayo, Saito, Koichi, Ooe, Norihisa, Isobe, Naohiko, Kaneko, Hideo, Nakatsuka, Iwao
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 03.01.2001; Amsterdam Elsevier Science
• Subjects: Binding assay; Binding, Competitive; Biological and medical sciences; Cell-Free System; Genes, Reporter; Humans; Insecticides - metabolism; Insecticides - toxicity; Kinetics; Luciferases - genetics; Luciferases - metabolism; Mammary Tumor Virus, Mouse - genetics; Medical sciences; Pesticides, fertilizers and other agrochemicals toxicology; Progesterone receptor; progesterone receptors; Pyrethrins - metabolism; Pyrethrins - toxicity; Pyrethroid insecticides; pyrethroids; Receptors, Progesterone - agonists; Receptors, Progesterone - antagonists & inhibitors; Receptors, Progesterone - metabolism; Reporter gene assay; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Toxicology; Transfection; Tumor Cells, Cultured; Two-hybrid assay; Reporter gene assay; Binding assay; Pyrethroid insecticides; Progesterone receptor; Two-hybrid assay; Human; Insecticide; Ligand; Toxicity; Pesticides; Pyrethroids; Molecular interaction; In vitro; Pollutant; Biological fixation; Reporter gene; Test; Test method; Progesterone; Hormonal receptor; Two hybrid method
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(00)00278-2

The progesterone receptor (PR) is associated with physiological events such as implantation and the maintenance of pregnancy. Recently, it has become a social concern that chemicals may exert agonistic or antagonistic effects on hormone receptors. Therefore, we examined the effects of various chemicals on the human PR, with a focus on pyrethroid insecticides, using three in vitro methods. Eight pyrethroid insecticides (fenvalerate, d-allethrin, d-phenothrin, prallethrin, empenthrin, permethrin, cypermethrin and imiprothrin), examples of environmental pollutants and positive control chemicals were subjected to a reporter gene assay (luciferase assay) using human breast cancer T-47D cells, a two-hybrid assay and a binding assay using the same whole cells or receptors (cell-free). In none of these did the eight pyrethroid insecticides show any binding to the PR, agonistic or antagonistic effects.