Aim:To investigate the possible mechanisms of ginsenoside Rgl promot-ing bone marrow stromal cell (BMSC) proliferation.Methods:BMSC were isolated from bone marrow of Sprague-Dawley rats and maintained in vitro.After stimulation with 1 μmol/L ginsenoside Rgl for the indicated time,the proliferation ability of BMSC were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and [3H]-thymidine incorporation assays.The es-trogen receptor (ER) binding activity of BMSC was determined by a specific ER antagonist and an ER binding assay.Furthermore,the influence of ginsenoside Rgl on the expression of ERa was investigated by RT-PCR and Weste blotting assays.Results:BMSC proliferation stimulated by 1 μmol/L ginsenoside Rgl can be completely blocked by 1 μmol/L ER antagonist ICI 182,780,or ERa-specific antagonist methylpiperidinopyrazole.Moreover,Rgl failed to displace the specific binding of [3H]17β-estradiol to BMSC cell lysates,suggesting that no direct interaction of Rgl with the ER is needed for its estrogenic effects.In addition,1 μmol/L Rgl had no effects on the expression of ERa in either the mRNA or protein levels.Conclusion:Our results indicate that ERa is essential for mediating the effects of Rgl on stimulating BMSC proliferation,which might involve the ligand/receptor-independent activation of ERα.