β-estradiol 17-valerate (EV) is a synthetic estrogen. In hormone replacement therapy drugs, it is widely used in combination with other steroid hormones.

Estradiol (10 nM) rapidly activates sphingosine kinase isoenzyme SphK1 as determined by enhanced phosphorylation on Ser225 in MCF-7 cells. Estradiol (20 nM) stimulates rapid release of sphingosine 1-phosphate (S1P) and dihydro-S1P from MCF-7 cells. SphK1 and estrogen receptor α are mainly responsible for formation of S1P and dihydro-S1P. Down-regulation of ABCC1 or ABCG2 with siRNAs or pharmacological inhibitors decreases Estradiol (10 nM)-mediated release of S1P or dihydro-S1P from MCF-7 cells. [1] Estradiol (10 nM) inhibits miR-21 expression in MCF-7 human breast cancer cells mediated by estrogen receptor α. Estradiol (10 nM) activates several miR-21 target gene reporters activity in MCF-7 cells through inhibiting miR-21 expression. Estradiol (10 nM) increases endogenous miR-21 target genes expression in protein but not RNA levels in MCF-7 cells. [2]

Estradiol (80 μg/kg/day, s.c.) significantly decreases the absolute numbers of total peritoneal cell and macrophages, characterized by a double F4/80- and CD11b-positive staining, in ovariectomized C57BL/6J mice. Estradiol (80 μg/kg/day, s.c.) enhances the LPS-induced expression of proinflammatory cytokines by TGC-elicited macrophages through inhibition of PI3K activity in ovariectomized C57BL/6J mice. Proinflammatory effect of Estradiol is abolished by downregulate estrogen receptor α activity in thioglycolate-elicited macrophages. [3]