Estrogen receptor related beta is expressed in human endometrium throughout the normal menstrual cycle

BACKGROUND Estrogen receptor related beta (ERRbeta, ESRRB/NR3B2) is an orphan receptor that shares significant sequence homology with estrogen receptors ERalpha and ERbeta. ERR family members are reported to exhibit constitutive transcriptional activity; however, little is known about the biological function of ERRbeta. In an attempt to delineate its role, we examined expression of ERRbeta in normal human endometrium, a tissue that undergoes cyclic remodelling under the influence of estrogen and progesterone. METHODS Well-characterized endometrial tissue (n = 31), including full-thickness biopsies, was obtained from women with regular menstrual cycles. RT-PCR was used to measure mRNA encoding ERRbeta, the peroxisome proliferator activated receptor gamma coactivators (PGC)-1alpha and beta and to determine whether ERRbeta splice variant mRNAs were expressed. ERRbeta was immunolocalized using both single and double antibody immunohistochemistry. RESULTS Total ERRbeta mRNA appeared higher in proliferative phase samples but results did not reach significance. Transcripts corresponding to the long- and short-splice variants of ERRbeta as well as PGC1alpha and beta were detected but ERRbetaDelta10 was absent. ERRbeta protein was localized to cell nuclei within multiple endometrial cell types including the glands, stroma, endothelium and immune cells, including uterine natural killer (uNK) cells and macrophages. Fluorescent immunohistochemistry revealed that some cells co-expressed ERRbeta and ERalpha or ERbeta, for example, endothelial and uNK cells were ERRbeta+/ERbeta+. CONCLUSIONS ERRbeta mRNA and protein are expressed in healthy human endometrium. Further studies are warranted to characterize the functional impact of ERRbeta on endometrial biology.