Some nonylphenol isomers show antiestrogenic potency in the MVLN cell assay

• Published in: Toxicology in vitro Vol. 24; no. 1; pp. 129 - 134
• Main Authors: Preuss, Thomas G., Gurer-Orhan, Hande, Meerman, John, Ratte, Hans Toni
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2010
• Subjects: Antagonists; Binding Sites; Branched isomer; Cell Line; Cell Line, Tumor; Dose-Response Relationship, Drug; Endocrine Disruptors - chemistry; Endocrine Disruptors - toxicity; Estradiol - pharmacology; Estrogen Antagonists - chemistry; Estrogen Antagonists - toxicity; Estrogen Receptor alpha - agonists; Estrogen Receptor alpha - antagonists & inhibitors; Estrogen Receptor alpha - metabolism; Female; Genes, Reporter - drug effects; Humans; Isomerism; Ligands; Nonylphenol; Phenols - chemistry; Phenols - toxicity; Receptor binding; Reporter gene assay; Xeno-hormone; Reporter gene assay; Antagonists; Xeno-hormone; Nonylphenol; Receptor binding; Branched isomer
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2009.08.017

It has been shown that nonylphenol (NP) isomers vary in their estrogenic potency. These differences may be due to varieties in receptor affinity, receptor activation, or activation/deactivation of non-receptor mediated side paths of reporter gene translation. In the present study we investigated the underlying mechanism of the different estrogenic potency of seven nonylphenol isomers. An estrogen receptor binding assay was conducted with the human estrogen receptor alpha (hERα). Additionally we co-incubated the nonylphenol isomers with two concentrations of 17β-estradiol (E2) in the MVLN cell assay to measure the potency of the isomers to compete with E2. No significant differences were found between the nonylphenol isomer binding affinities for the hERα. The IC
50 were in the range of 2.1–8.1
×
10
−6
M and the binding affinity relative to estradiol (set to 1) were between 2.6 and 6.7
×
10
−3. Only two test items (
p353-NP and
p-NP) were able to increase the estrogenic response of 100
pM estradiol. The response of the other isomers co-incubated with 100
pM E2 showed varying degrees of inhibition of the response in the MVLN reporter gene assay. Thus, it appears that all isomers bind to the ER but some are partial agonists while others are antagonists in the MVLN reporter gene assay.