Identification of coregulators influenced by estrogen receptor subtype specific binding of the ER antagonists 4-hydroxytamoxifen and fulvestrant.

The aim of the present study was to investigate modulation of the interaction of ERα and ERβ with coregulators in the ligand dependent responses induced by the ER antagonistic compounds 4OHT and fulvestrant. Comparison with the modulation index (MI) profiles for the ER agonist estradiol (E2) will elucidate whether differences in the (ant)agonist dependent interaction of ERα and ERβ with coregulators expressed in MI profiles contribute to the differences in (ant)agonist responses. To this end, the selected ER antagonistic compounds were first characterized for intrinsic relative potency and efficacy towards ERα and ERβ using ER selective U2OS reporter gene assays, and subsequently tested for ligand dependent modulation of the interaction of ERα and ERβ with coregulators using the MARCoNI assay.

Cell proliferation and modulation of interaction of estrogen receptors with coregulators induced by ERα and ERβ agonists.

The aim of the present study was to investigate modulation of the interaction of the ERα and ERβ with coregulators in the ligand responses induced by estrogenic compounds. To this end, selective ERα and ERβ agonists were characterized for intrinsic relative potency reflected by EC50 and maximal efficacy towards ERα and ERβ mediated response in ER selective reporter gene assays, and subsequently tested for induction of cell proliferation in T47D-ERβ cells with variable ERα/ERβ ratio, and finally for ligand dependent modulation of the interaction of ERα and ERβ with coregulators using the MARCoNI assay, with 154 unique nuclear receptor coregulator peptides derived from 66 different coregulators. Results obtained reveal an important influence of the ERα/ERβ ratio and receptor selectivity of the compounds tested on induction of cell proliferation.

Proliferation assays for estrogenicity testing with high predictive value for the in vivo uterotrophic effect.

Proliferation assays based on human cell lines are the most used in vitro tests to determine estrogenic properties of compounds. Our objective was to characterise to what extent these in vitro tests provide alternatives for the in vivo Allen and Doisy test, a uterotrophic assay in immature or ovariectomised rodents with uterus weight as a crucial read-out parameter. In the present study four different human cell lines derived from three different female estrogen-sensitive tissues, i.

Role of surface charge and oxidative stress in cytotoxicity of organic monolayer-coated silicon nanoparticles towards macrophage NR8383 cells.

Background: Surface charge and oxidative stress are often hypothesized to be important factors in cytotoxicity of nanoparticles. However, the role of these factors is not well understood. Hence, the aim of this study was to systematically investigate the role of surface charge, oxidative stress and possible involvement of mitochondria in the production of intracellular reactive oxygen species (ROS) upon exposure of rat macrophage NR8383 cells to silicon nanoparticles.