Effect of 17β-estradiol on VEGF and HIF-1α mRNA expressions in bovine retinal vascular endothelial cells

Objective To investigate the effect of the physiological level of estradiol on mRNA expressions of the vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) in bovine retinal vascular endothelial cells (BRECs) under different oxygen conditions. Methods mRNA expressions of VEGF and HIF-1α were determined by reverse transcription polymerase chain reaction (RT-PCR) in BRECs, with E2(10-12,10-10,10-8 mol/L)or phosphate-buffered saline (PBS) and estrogen receptor antagonist tamoxifen (10-7 mol/L) under normoxia and hypoxia after 8 hours and 24 hours. Results ① Under hypoxia, gene expressions of VEGF and HIF-1α mRNA in BRECs more significantly increased than in the controls(P0.05). There were evident positive correlations between the expressions of VEGF mRNA and HIF-1α mRNA(r=0.82). ② After BRECs were treated with the indicated concentrations of E2 under normoxia for 24 hours, the expression of VEGF mRNA increased in a dose-dependent manner between 10-12～-8 mol/L (P0.05). After BRECs being treated with 10-8 mol/L E2 8 hours and 24 hours, the expression of VEGF mRNA was increased in a time-dependent manner(P0.05). Whereas E2 did not affect the expression of HIF-1αmRNA(P0.05). ③ After BRECs were treated with the indicated concentrations of E2 under hypoxia for 24hours, the expressions of HIF-1α mRNA and VEGF mRNA decreased in a dose-dependent manner between 10-12～-8 mol/L(P0.05). After BRECs were treated with 10-8 mol/L E2 for 8 hours and 24 hours, the expressions of HIF-1α mRNA and VEGF mRNA decreased in a time-dependent manner (P0.05). ④ An overdose of tamoxifen (10-7 mol/L) reversed the effect of E2(10-8 mol/L) (P0.05). Conclusions The physiological level of E2 has a contrast effect on VEGF mRNA in a dose-and time-dependent manner based on oxygen conditions. E2 increases the gene expression of VEGF in BRECs under normoxia, whereas E2 decreases the gene expression of VEGF in BRECs through HIF-1α under hypoxic conditions.