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Extending an in vitro panel for estrogenicity testing: the added value of bioassays for measuring antiandrogenic activities and effects on steroidogenesis.

ABSTRACT: In the present study, a previously established integrated testing strategy (ITS) for in vitro estrogenicity testing was extended with additional in vitro assays in order to broaden its sensitivity to different modes of action resulting in apparent estrogenicity, i.e., other than estrogen receptor (ER) binding. To this end, an extra set of 10 estrogenic compounds with modes of action in part different from ER binding, were tested in the previously defined ITS, consisting of a yeast estrogen reporter gene assay, an U2OS ERα CALUX reporter gene assay and a cell-free coregulator binding assay. Two androgen reporter gene assays and the enhanced H295R steroidogenesis assay were added to that previous defined ITS. These assays had added value, as several estrogenic model compounds also elicited clear and potent antiandrogenic properties and in addition also showed effects on steroidogenesis that might potentiate their apparent estrogenic effects in vivo. Adding these assays, examining mechanisms of action for estrogenicity apart from ERα binding, gives a more complete and comprehensive assessment of the ability of test compounds to interfere with endocrine signaling. It was concluded that the extended ITS will go beyond in vivo estrogenicity testing by the uterotrophic assay, thereby contributing to the 3R-principles.

SUBMITTER: Wang S

PROVIDER: S-EPMC4833097 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Extending an in vitro panel for estrogenicity testing: the added value of bioassays for measuring antiandrogenic activities and effects on steroidogenesis.

Wang Si S Rijk Jeroen C W JC Besselink Harrie T HT Houtman René R Peijnenburg Ad A C M AA Brouwer Abraham A Rietjens Ivonne M C M IM Bovee Toine F H TF

Toxicological sciences : an official journal of the Society of Toxicology 20140613 1

In the present study, a previously established integrated testing strategy (ITS) for in vitro estrogenicity testing was extended with additional in vitro assays in order to broaden its sensitivity to different modes of action resulting in apparent estrogenicity, i.e., other than estrogen receptor (ER) binding. To this end, an extra set of 10 estrogenic compounds with modes of action in part different from ER binding, were tested in the previously defined ITS, consisting of a yeast estrogen repor ...[more]

PMID: 24928889

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Dataset Information

Extending an in vitro panel for estrogenicity testing: the added value of bioassays for measuring antiandrogenic activities and effects on steroidogenesis.

Publications

Extending an in vitro panel for estrogenicity testing: the added value of bioassays for measuring antiandrogenic activities and effects on steroidogenesis.

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