Estrogen receptors (ER) classically function as transcription factors regulating gene expression. More recently, evidence has continued to accumulate that ER additionally serve numerous important functions remote from the nucleus in a variety of cell types, particularly in non-reproductive tissues. The identification of post-translational modifications of ERα and protein-protein interactions with the receptor that are critical to its non-nuclear functions has afforded opportunities to gain greater insights into these novel non-genomic roles of the receptor. The development of a stable ligand that selectively activates non-nuclear ER has also been invaluable. In this review focused on ERα, recent new understanding of the processes underlying non-nuclear ER action and their in vivo consequences will be discussed. Further research into the non-nuclear capacities by which ER modulate cellular behavior is essential to ultimately harnessing these processes for therapeutic gain in numerous disease contexts.
Keywords: Bone mineralization; Caveolae; Endothelium; Estrogen receptor; Nitric oxide synthase; Vascular smooth muscle.
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