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  • Title: Activation of steroid hormone receptors: Shed light on the in silico evaluation of endocrine disrupting chemicals.
    Author: Chen Q, Tan H, Yu H, Shi W.
    Journal: Sci Total Environ; 2018 Aug 01; 631-632():27-39. PubMed ID: 29522903.
    Abstract:
    Endocrine disrupting chemicals (EDCs) are of great concern given their potential influence on the endocrine system. In silico methods for the evaluation of EDCs have been widely recognized. However, subcellular molecular mechanisms of action, such as ligand-receptor interactions, receptor conformational switch and protein-protein interactions, are needed for the development of mechanism-based in silico models. Here, molecular mechanisms of action for steroid hormone receptors (SHRs), the important targets of EDCs, are systematically reviewed. Ligand binding and ligand-receptor interactions are required for SHR activation, and facilitate the nuclear translocation and the dimerization of SHRs. Coregulator recruitment results from conformational switch of SHR, which regulates the transcription and results in either an agonistic or an antagonistic effect. EDCs potentially interfere with SHRs by influencing ligand-receptor interactions, nuclear translocation, dimerization and coregulator recruitment. These new findings shed light on the development of mechanism-based computational models for the evaluation of EDCs.
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