Figure 2

Genomic and nongenomic effects of estrogen. When estrogen (E2) binds estrogen receptors (ER) in the cytoplasm, they undergo homodimerization, translocation to the nucleus, and bind to estrogen responsive element (ERE) of genes and initiate specific gene transcriptions, acting like a transcription factor. Alternatively, the E2-bound GPR30 may initiate activation of protein kinases such as PKA, PKB, and PKC. This may be followed by the activation of intracellular E2-bound ER (30), other transcription factors such as cAMP response element-binding protein (CREB) or mobilization of intracellular calcium stores. The latter processes which are independent of ER, also known as nongenomic effect, facilitate a rapid response to stimuli. CREB binds to cAMP response element (CRE) to initiate transcription. A subset of ERs also associate with plasma membrane and interact with transmembrane growth factor receptors such as insulin-like growth factor receptor I, and epidermal growth factor receptor to induce nongenomic effects by protein-protein interactions (129). Recently it has been shown that PKA activation and Bcl-2 expression in the liver of E2-treated trauma-hemorrhage rats are initiated by E2 binding to GPR30 (130).