In-vitro screening of the antiestrogenic activity of chemicals.
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.


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.
Navas
José M
JM
Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Department of Environment, Madrid, Spain. jmnavas@inia.es
Segner
Helmut
H
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D052244:Endocrine Disruptors / Q000494:pharmacology* / Q000633:toxicity; D004965:Estrogen Antagonists / Q000494:pharmacology* / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D020239:Receptor Cross-Talk / Q000187:drug effects; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation
D052244:Endocrine Disruptors; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen