Endocrine Abstracts

Steroid receptors are members of a family of ligand-activated transcription factors that mediate tissue responses to a variety of endocrine stimuli. Using the human endometrium as a paradigm of a steroid responsive tissue, we aimed to characterise the expression and function of the oestrogen-receptor related orphan nuclear receptors (ERR) alpha and beta. ERRs share significant sequence homology with oestrogen receptors (ER) alpha and beta but are unable to bind oestradiol. They are reported to regulate gene expression by binding to the ER response elements (ERE) or SF1 binding sites (SFRE) in gene promoters. In the present study we used immunohistochemistry and Taqman quantitative RT-PCR to determine the expression pattern of ERRalpha and ERRbeta in human endometrium. Both ERRs were detected in the stromal and epithelial compartments, and were co-expressed with ERalpha and/or ERbeta in a number of different cell types. Using transient transfection assays with luciferase-linked reporters in a range of cell types we assessed the impact of ERR expression on ERE- and SFRE-mediated gene induction. Surprisingly, in contrast to previous reports, we failed to observe any evidence of constitutive activation by the receptor on reporter gene expression. However we were able to modulate reporter gene activity when cells were co-transfected with nuclear receptor coactivators such as the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1alpha). In addition, preliminary data suggest that expression of ERRs can modulate ER-dependent activation of ERE-mediated gene expression. Taken together this data suggests that within cells, including those of the human endometrium, the ERRs may modulate steroid induced ER activation of gene expression through sharing of nuclear receptor coactivators or by direct interaction with ERE promoters.