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

Estrogen receptor related beta (ERR beta, ESRRB/NR3B2) is an orphan receptor that shares significant sequence homology with estrogen receptors ER alpha and ER beta. ERR family members are reported to exhibit constitutive transcriptional activity; however, little is known about the biological function of ERR beta. In an attempt to delineate its role, we examined expression of ERR beta in normal human endometrium, a tissue that undergoes cyclic remodelling under the influence of estrogen and progesterone. 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 ERR beta, the peroxisome proliferator activated receptor gamma coactivators (PGC)-1 alpha and beta and to determine whether ERR beta splice variant mRNAs were expressed. ERR beta was immunolocalized using both single and double antibody immunohistochemistry. Total ERR beta mRNA appeared higher in proliferative phase samples but results did not reach significance. Transcripts corresponding to the long- and short-splice variants of ERR beta as well as PGC1 alpha and beta were detected but ERR beta Delta 10 was absent. ERR beta 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 ERR beta and ER alpha or ER beta, for example, endothelial and uNK cells were ERR beta+/ER beta+. ERR beta mRNA and protein are expressed in healthy human endometrium. Further studies are warranted to characterize the functional impact of ERR beta on endometrial biology.