PRECLINICAL STUDIES ON NONHUMAN PRIMATE ENDOMETRIAL XENOGRAFTS

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Endometriosis is a condition where endometrium-like tissue forms lesions at sites outside the uterus. Our goal is to test potential therapies for endometriosis. To do this we have developed a model in which we transplant macaque endometrium into immunodeficient SCID mice, which are incapable of rejecting xenografts. The endometrial xenografts grow in response to estradiol (E2) and undergo cyclic breakdown similar to endometriosis in women. Recent studies indicate estrogen receptor (ER) alpha mediates the proliferative effects of E2 in endometriosis and that ER beta could act as an inhibitor of ER alpha action. Other studies indicate that progesterone antagonists (PA) also block E2 stimulated endometrial growth. Our aim in this study was to assess the safety and efficacy of ER beta agonist therapy and progesterone antagonist therapy for in our xenograft model prior to conducting clinical trials on endometriosis in women. We compared the effects of two ER beta agonists, a potent antiestrogen (ER beta plus ER alpha antagonist) and a new generation PA on E2 stimulated growth in ectopic endometrium. We report that both the ER antagonist, and PA blocked E2 stimulated growth of ectopic primate endometrium in the mice. However, ER beta agonists had no effect on endometrial xenograft growth.