Abstract: 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. MethodsmRNA expressions of VEGF and HIF-1α were determined by reverse transcription polymerase chain reaction (RTPCR) in BRECs, with E2（10-12,10-10,10-8mol/L）or phosphatebuffered saline (PBS) and estrogen receptor antagonist tamoxifen (10-7mol/L) under normoxia and hypoxia after 8 hours and 24 hours. Results① Under hypoxia, gene expressions of VEGF and HIF-1α mRNA in BRECs more significantly increased than in the controls(P＜0.05). 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～-8mol/L (P＜0.05). After BRECs being treated with 10-8mol/L E2 8 hours and 24 hours, the expression of VEGF mRNA was increased in a time-dependent manner(P＜0.05). Whereas E2 did not affect the expression of HIF-1αmRNA（P＞0.05）. ③ After BRECs were treated with the indicated concentrations of E2 under hypoxia for 24 hours, the expressions of HIF-1α mRNA and VEGF mRNA decreased in a dose-dependent manner between 10-12～-8mol/L(P＜0.05). After BRECs were treated with　10-8mol/L E2 for 8 hours and 24 hours, the expressions of HIF-1α mRNA and VEGF mRNA decreased in a timedependent manner (P＜0.05). ④ An overdose of tamoxifen (10-7mol/L) reversed the effect of E2(10-8mol/L) (P＜0.05). ConclusionsThe 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.

Key words: Retinal vessels, Endothelial cells, 17β-estradiol, Vascular endothelial growth factor, Hypoxia-inducible factor-1α