Estrogen receptors, including ERα and ERβ, contain DNA binding and ligand binding domains and are critically involved in regulating the normal function of reproductive tissues. ERα and ERβ have been shown to be differentially activated by various ligands. Phosphorylation of serines 104 and 106, located in the N-terminal transcription activation function-1 domain (AF-1), plays a large role in regulating ER alpha activity. Evidence suggests that ERα and ERβ may be regulated by distinct mechanisms even though they share many functional characteristics.