Endocrine Abstracts

The oestrogen-receptor related orphan nuclear receptors (ERR) share significant sequence homology with oestrogen receptors (ER) alpha and beta but are unable to bind oestradiol. They are reported to constitutively regulate gene expression by binding to the ER response elements (ERE) or SF1 binding sites (SFRE) in gene promoters. However recent evidence from transgenic animal models point towards a role of these orphan nuclear receptors as regulators of energy-producing metabolic pathways and not as mediators of oestrogen signalling. We used immunohistochemistry to study the cellular localisation of one ERR family member, ERRα, in human endometrium biopsies as well as quantitative real time PCR to measure its expression levels during the ovarian cycle. There appeared to be an up-regulation of the transcript levels during the mid-secretory phase, which almost reached statistical significance. Further we observed a robust induction of ERRα transcripts upon in vitro decidualisation of human endometrial stromal cells. Ectopic ERRα overexpression in the endometrial adenocarcinoma Ishikawa cell line resulted in up-regulation in a variety of pathways that may influence energy status in the endometrial epithelium. Together these findings are consistent with a possible role for ERRα in the control of energy producing metabolism in the human endometrium. They also suggest a mechanistic explanation for a previously reported surge in energy generating processes concomitant with the implantation window.