This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Our broad goal is to investigate novel drug therapies for endometriosis. Macaque endometrium can be auto-transplanted to ectopic intraabdominal and subcutaneous sites. These endometrial grafts provide an excellent endometriosis-like model system for preclinical testing of novel anti-endometriotic therapies. Mineralocorticoid receptor (MR) has been identified as a potential target for therapies for endometriosis in women. In preliminary studies we showed that Spironolactone (an anti-mineralocorticoid) can block estrogen-stimulated cell proliferation and growth in both ectopic and eutopic endometrium. Spironolactone does not bind to the estrogen receptor, but does interact with androgen receptor (AR) as an anti-androgen. It is unclear if the antiproliferative effect of Spironolactone is through action on MR or through AR. This study will compare the effect of Spironolactone (anti-MR and anti-AR) with Eplerenone (an anti-MR with no known affinity for AR) on estrogen action in eutopic and ectopic endometrium in rhesus macaques. Since little is known regarding the effects of androgen blockade in endometriotic tissues, the study will be extended to specifically investigate full blockade of AR with Casodex (a pure anti-androgen) in our model.
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