Objective To investigate the effect of 17β-estradiol on the proliferation of thyroid stem/ progenitor cells.Methods In thyroid stem/progenitor cells derived from nodular goiters,the effects of 17 β-estradiol on thyrosphere formation,estrogen receptor (ER) expression,cyclin D1 expression,and mitogen activated protein kinase (MPAK) pathway were analysed by BrdU ELISA,conventional and realtime PCR,immunofluorensence staining,and Western blot.Results 17β-estradiol induced thyrosphere formation and proliferation of thyroid stem/ progenitor cells.ER-α and ER-β were expressed in thyroid stem and progenitor cells with higher mRNA expression level of ER-α compared to differentiated thyrocytes (8.85-±0.81 vs 1.10 ±0.35,P＜0.01).Stimulation by 1 mmol/L 17β-estradiol increased cyclin D1 mRNA expression and ERK phosphorylation levels,which was blocked by an ER antagonist,ICI 182780.Conclusion Estrogen stimulated the growth of stem cells derived from thyroid nodules via estrogen receptor,suggesting the relevance of increased thyroid stem cell proliferation with higher prevalence of thyroid nodules in women.