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[4] At the cellular level, free estradiol diffuses through cell membranes and binds to intracellular estrogen receptors and , which upon ligand activation dimerize and translocate to estrogen-response elements on nuclear DNA, modulating transcription of genes governing reproductive tract integrity, thermoregulation, bone metabolism, and vascular endothelial function

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TGR5-deficient mice have increased colonic mucosal permeability, through disruption of epithelial tight junctions (176)