Study On Correlativity Of Estrogen Receptor β With Endometriosis In BERKO And SCID Mice Models

Objective: To investigate the distribution of estrogen receptor isoforms, COX-2 and OTR in normal endometrium and muscles, the eutopic endometrium in endometriosis, ovarian endometriosis cysts and adenomyosis, research the effect of ERβin endometriosis and adenomyosis by the endometriosis animal model in ERβknockout mice and SCID mice, provide the data of treating endometriosis with ERβagonist WAY-200070.Methods: 1) Samples of normal endometrium and muscles, eutopic endometrium of endometriosis, adenomyotic focus and ovarian endometriotic cysts were collected. Employed Western blotting, RT-PCR and immunohistochemical method to investigate the expression of ERα, ERβ, COX-2 and OTR in different tissues. 2) To set up endometriosis animal model in ERβknockout mice and study the effect ot ERβon the endometriosis. 3) SCID mice were implanted with tissue fragments of normal human endometrium, eutopic endometrium of endometriosis, adenomyotic lesion and ovarian endometriosis cysts respectively. After establishment endometriosis model, tne mice were treated with ERβagonist WAY-200070 for 14 days. Upon euthanasia, the number of lesions and their weight were measured.Results: 1) There were expression of ER in various tissues, the expression of ERαshowed much stronger than ERβ. The expression of OTR and COX-2 in the eutopic endometrium of endometrisis significantly higher than in normal endometrium, which were correlative with ERαand no relation with ERβ. 2) Comparing with the protein level in adenomyotic focus, the level of ERαand ERβwere much lower and the level of OTR and COX-2 were much higher than in other ectopic focuses by Western blotting and RT-PCR. But the expression of ERαand ERβwere higher in the ectopic focus and the eutopic endometrium than in the normal endometrium by immunohistochemical method.3) Comparing with the protein level in the endometric cyst, the level of OTR and COX-2 were much higher and ERαwas much lower than in the nomal and eutopic endometrium, the level of ERβwas not different in various tissues.4) The endometriotic models in ERβknockout mice were not different camparing with the cognate mice (P>0.05) , but weight of the models in the mice with ovariectomized were much lower than in the mice without ovariectomized(P<0.05 ) . 5) The weight of endometriotic models were reduced significantly in the SCID mice implanted with tissue fragments of normal human endometrium, eutopic endometrium of endometriosis and ovarian endometriosis cysts (P<0.05 ) , but were not diffrrent cmparing the mice treated with ERβagonist WAY-200070 to the control groups (P>0.05) . However, there was difference in the adenomyotic focus compare with the control group(P=0.03) .Conclusion: There are expression of ER in normal human endometriumand muscles, eutopic endometrium of endometriosis, adenomyotic lesion and ovarian endometriosis cysts, but the protein level of ERβis much lower than ERα. There is not difference in the endometriotic models between ERβknockout mice and homolog mice. The ERβagonist WAY-200070 do not significantly suppress the endometriotic lesions in SCID mice comparing with the control groups. So it implys that ERβdoes not play an important role in endometriosis and adenomyosis.