In-vitro screening of the antiestrogenic activity of chemicals

Abstract

Background: Many chemicals have the potential to interfere with the endocrine systems of humans and wildlife, leading to adverse health effects. In the tiered testing strategies developed for regulatory hazard assessment, in-vitro screens could serve for prioritisation of compounds and for guiding subsequent testing. Objective: To describe in-vitro assays to detect antiestrogenic activity of chemicals. Methods: Antiestrogenicity was considered in this review as any inhibition or reduction of estrogen-induced processes due to interference with the normal functioning of the estrogen receptor pathway. Accordingly, in-vitro screening assays for antiestrogenicity have to consider all the possible mechanisms by which this inhibition may occur. Such assays include binding assays, cell proliferation assays, reporter gene assays, and gene activation/protein production assays. Results/conclusions: While binding assays appear to be of limited value in assessing antiestrogenicity, assays using differentiated cells with metabolic competence and a varied receptor/regulatory factor equipment have the capability to detect various modes of antiestrogenic action.