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The estrogen receptor (ER-alpha) is a nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. ER-alpha can activate the transcriptional activity of TFF1. ER-alpha binds DNA as a homodimer, and can form a heterodimer with ESR2. ER-alpha interacts with FOXC2, MAP1S, SLC30A9, UBE1C and the coactivators NCOA3, NCOA5, NCOA6, and NCOA7. Genetic variations in ER-alpha are correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture.