Ovarian granulosa cell tumours (GCT) express abundant estrogen receptor β (ERβ). Despite the high expression, ERβ signalling is transrepressed by the pro-survival transcription factor, NF-κB. Our preliminary data has suggested that activation of ERβ using selective estrogen receptor modulators (SERMs) may circumvent this transrepression. We hypothesise that the ERβ-specific ligands, diarylpropionitrile (DPN) and indazole, can circumvent NF-κB transrepression in KGN cells and subsequently activate ERβ signalling. In this study, we investigated the ability of the ER isoform-specific ligands DPN (100 nM), indazole (500 nM), bazedoxifene (10 nM), ethinyl estradiol (EE) (10 nM), and propyl pyrazole triol (PPT) (1 nM), to transactivate ER in a GCT-derived cell line (KGN). The endogenous physiological ER ligand 17β-estradiol (100 nM) was used as a control. KGN cells were transfected with estrogen-responsive reporter vector construct (ERE2-luc) either alone or with ERα or ERβ expression vectors, to compare the effects of the individual ligands on endogenous and exogenous receptors. We found that the ligands had no effect on the endogenous ER, suggesting transrepression. However, we found induction of the reporter by exogenous ER with 17β-estradiol (3-fold (ERα); 7-fold (ERβ)), DPN (4-fold (ERα and ERβ)), indazole (3-fold (ERβ)), EE (9-fold (ERα); 8-fold (ERβ)), and PPT (5-fold (ERα); 8-fold (ERβ)). Interestingly, the highest activation of both exogeneous receptors, was by EE (9- and 8-fold respectively), despite being widely known as only an ERα agonist. EE is commonly used in the oral contraceptive pill (OCP), has previously been shown to decrease granulosa cell mass in women who used EE-containing OCP. We speculate that these effects are likely to be ERβ-mediated due to this receptor being the predominant ER in these cells. These findings will add to our understanding on whether these ligands have a potential therapeutic use for ovarian GCT.