β-Estradiol (Synonyms: β-Estradiol, Estradiol, 17β-Oestradiol, E2)

Estradiol is the main sex hormone present in females and also present in males as an active metabolic product of testosterone. It is the major estrogen which impacts on reproductive and organs such as the bones in humans [1].
As a main form of estrogen, estradiol interacts with two estrogen receptors (ER), i.e ERα and ERβ, which exert the effects by diverse signaling pathways that mediate the nongenomic and genomic cases.
With treatment of estradiol, ERβ-specific effects on gene expression have been investigated in three different cell lines lacking expression of endogenous ERα and ERβ, namely U2OS (25), HEK293 (26), and　Hs578T (23) cells. 17 genes of the 76   ERβ-regulated genes were commonly regulated by both ERα and ERβ, suggesting that the transcriptional effects of estradiol via ERα or ERβ are largely distinct in U2OS cells. 95 and 61  genes were identified as ERβ-regulated genes in Hs578T cells and HEK293 cells in a 24-h estradiol treatment, respectively. Only three genes (PTGER4, ENPP2, and DKK1)　commonly regulated in both HEK293 and Hs578T cells, suggesting that ERβ evokes distinct gene responses in different　types of target cells. By using estradiol, new roles of ERβ signaling was established, including protective functions in the epithelial-mesenchymal transition,as well as regulation of cell proliferation in the colon [2].
Animal experiments have shown the protective effects of estrogens in cardiovascular diseases. In mice and in vitro in human aorta endothelial cells, treatment with estradiol increases the expression of mitochondrial superoxide dismutase significantly. Estradiol up-regulates superoxide dismutase by tethering of estrogen receptor to Sp1 and the increased binding of Sp1 to GC-box on the superoxide dismutase promoter, where ERα responses estradiol-mediated activation of gene, and ERβ maintains a level of basal gene expression. Investigation of the reduction in PS levels caused by E2 in HepG2-ERα cells showed E2 repressed the production of mRNA and antigen of PS. In addition, E2 might repress PROS1 transcription depending upon ERα-Sp1 recruiting transcriptional repressors in HepG2-ERα cells and, the high levels of E2 resulting in reduced levels of plasma PS would be a risk for deep venous thrombosis in pregnant women [1,3].
References:
[1]. Liu ZY, Gou YL, Zhang HY, et al. Estradiol improves cardiovascular function through up-regulation of SOD2 on vascular wall. Redox Biology, 2014, 3: 88-99.
[2]. Zhao CY, Dahlman-Wright K, Gustafsson J. Estrogen signaling via estrogen
receptor β*. The Journal Of Biological Chemistry, 2010, 51: 39575–39579.
[3]. Suzuki A, Sanda N, Miyawaki Y, et al. Down-regulation of pros1 gene expression by 17 beta-estradiol via estrogen receptor alpha (er alpha)-sp1 interaction recruiting receptor-interacting protein 140 and the corepressor-hdac3 complex. Journal Of Biological Chemistry, 2010, 285(18): 13444-13453.