Objective To detect the effects of estrogen receptor antagonists on pituitary GH3 cell proliferation,apoptosis,prolactin (PRL) secretion,and estrogen receptor ( ER ) isoforms expressions,and to investigate the mechanisms of exogenous estrogen( 17β -estradiol,E2 ) in prolactinoma tumorigenesis and development.Method Different methods had been used to test the GH3 cells cultured with hormone -deprivedp rat PRL ELISA kit was applied to the detection of PRL secretion;flow cytometry was used to detect OHTam and ICI induced cell apoptosis; Western blot analysis was applied to the detection of ERo and ERβ expressed in GH3 cells.Results E2 had significant stimulatory effect on growth of GH3 cells,and the effect worked even at low concentration of 10 - 12mol/L compared to the hormone - deprived medium cultured GH3 cells.OHTam and ICI could inhibit GH3 cell proliferation as dose -dependent manner,when the concentration rising to 10-6 mol/L,the cell proliferation index were 0.62 and 0.47 respectively;OHTam and ICI could suppressed the stimulatory effect of E2 on GH3 cell proliferation.All the results had statistical significance ( P < 0.05 ).E2 could increase PRL secretion in GH3 cells and the effect appeared to be dose - dependent;OHTam and ICI decreased PRLsecretion,and could inhibit the promotion effect of E2.OHTam and ICI could induced GH3 cells apoptosis,mostly early apoptosis.The expression of ERα and ERβ in GH3 cells were observed,E2 up - regulated ERβ expression level,and ICI obviously down -regulated the expression of ERα,however,OHTam couldn't regulate the expression levels of ERα and ERβ.Conclusion Estrogen receptor antagonists can inhibit GH3 cell proliferation and PRL secretion,induce cell apoptosis,and inhibit the effect of E2,and thus,generate antitumor effects.In addition,ICI can down - regulate the expression of ERα,and that may be related to its antitumor effects. Key words: Prolactinoma; Estrogens; Prolactin; Receptor, estrogen; Estrogen receptor antagonist