Expression of estrogen receptor coactivators in the rat uterus

Nuclear receptor coactivators associate in a ligand-dependent manner with e strogen receptors (FR) and other nuclear receptors, and they enhance ligand -dependent transcriptional activation. This study examined basal coactivato r expression in rat uterus to investigate if expression of these genes is r egulated by estradiol-17 beta or tamoxifen. Ovariectomized mature and immat ure rats were injected with estradiol-17 beta, tamoxifen, or vehicle (i.e., sesame oil) alone. Uteri were collected and analyzed for changes in coacti vator mRNA expression using Northern blot and in situ hybridization analyse s. Constitutive uterine mRNA expression of switch protein for antagonist (S PA), SRC-1, GRIP1, RAC3, RIP140, and p300 mRNAs was observed in control ute ri, and treatment with ER ligands did not alter coactivator mRNA levels. Th e data suggest that expression of these coactivator genes is not sensitive to estradiol or tamoxifen in the rat uterus. No cell type-specific pattern of expression was apparent in uterine sections from mature and immature rat s; however, silver grains were more abundant in luminal and glandular epith elial cells compared with the stroma and myometrium, indicating that coacti vator mRNA levels vary among the uterine compartments. Thus, to our knowled ge, we show for the first time that there is constitutive expression of sev eral uterine nuclear receptor coactivators in a physiological setting that remains insensitive to estrogenic regulation. Furthermore, we speculate tha t higher constitutive levels of coactivator expression in glandular and lum inal epithelial cells may be associated with increased hormonal responsiven ess by these uterine compartments.