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 (hER alpha). Additionally we co-incubated the nonylphenol isomers with two concentrations of 17 beta-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 hER alpha. The IC(50) were in the range of 2.1-8.1 x 10(-6) M and the binding affinity relative to estradiol (set to 1) were between 2.6 and 6.7 x 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. (C) 2009 Elsevier Ltd. All rights reserved.