Exposure to estrogen elicits a conformational change of the receptors that causes dissociation from chaperones, heat shock protein 90 (Hsp90) (McEwan 2009). Estrogen–bound receptors are dimerized and translocated into nucleus leading to direct interaction with specific DNA sequences (Figure 3–11), known as estrogen responsive elements (ERE) (Dickson and Eisenfeld 1980; Murayama and Fukai 1982; Levin 2005). The ERE contains 13 bp reverted consensus sequence 5’ GGTCAnnnTGACC–3’, which functions as an enhancer for ERE–containing genes (Rollerova and Urbancikova 2000). In parallel to the binding of the estrogen–ER complex to the ERE, many co–activators and/or co–repressors are recruited to bind at the hydrophobic pocket of ER, enhancing or repressing its transcriptional activity (Rollerova and Urbancikova 2000). The relationship between the estrogen, receptor, and co–activators and/or repressors determines the specificity of cellular responses (Kumar et al. 2004). This process requires at least 2 h for modulating the direct transcription of the genes via activation of ERs. There are approximately 70,000 genes in human and mouse genomes that present ERE on the promoter region (Bourdeau et al. 2004), suggesting the diverse functions of estrogen. Moreover, estrogen–ER complex can indirectly bind with other promoter (non–ERE) through other protein–protein interaction with other DNA–binding transcription factor, e.g., Ap–1 and Sp–1, which known as indirect genomic action of estrogen.