Insights into the activation mechanism of human estrogen-related receptor γ by environmental endocrine disruptors.

ABSTRACT: The estrogen-related receptor γ (ERRγ, NR3B3) is a constitutively active nuclear receptor which has been proposed to act as a mediator of the low-dose effects of a number of environmental endocrine-disrupting chemicals (EDCs) such as the xenoestrogen bisphenol-A (BPA). To better characterize the ability of exogenous compounds to bind and activate ERRγ, we used a combination of cell-based, biochemical, structural and computational approaches. A purposely created stable cell line allowed for the determination of the EC50s for over 30 environmental ERRγ ligands, including previously unknown ones. Interestingly, affinity constants (Kds) of the most potent compounds measured by isothermal titration calorimetry were in the 50-500 nM range, in agreement with their receptor activation potencies. C

SUBMITTER: Thouennon E 

PROVIDER: S-EPMC11105698 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature