Endocrine Abstracts

Oestrogens are essential regulators of fertility in women. They induce changes in uterine cell function by binding to oestrogen receptors (ERs) two of which (ERα and ERß) have been identified. ERα and ERß share significant sequence homology with three other steroid receptor superfamily members that are known as oestrogen related receptors alpha (ERRα), beta (ERRß) and gamma (ERRγ). ERRs bind as monomers to the sequence TNAAGGTCA and as dimers to the consensus oestrogen response element (ERE).

We have previously mapped the pattern of expression of ERα, ERß and an ERß variant (ERß2) within the endometrium and demonstrated cell-specific patterns of expression. In the present study we have investigated whether ERRα and ß are expressed in the human endometrium as the first step in determining what impact they might have on gene expression. Full thickness endometrial biopsies were obtained from women with regular menstrual cycles. ERRα and ß were immunolocalised with antibodies obtained from Abcam. Immunopositive cell nuclei were detected at all stages of the normal menstrual cycle; ERRß immunostaining was more intense than that of ERRα. When expression of ERRß was compared with that of ERα using double fluorescent immunohistochemistry cell-specific patterns of expression were revealed. For example, endothelial cells were ERRß+/ERα− and whilst most stromal cells were ERRß+/ERα+ there was also a population that were ERRß+/ERα− that may represent one (or more) of the immune cell types that are prominent during the secretory phase.

In conclusion, we have demonstrated for the first time, that ERRs are expressed in the human uterus during the normal menstrual cycle. Future studies will use endometrial cells (primary and immortalised) to determine the impact of ERRs on oestrogen-regulated gene expression in the endometrium.