Steroid receptor expression in uterine natural killer cells

The endometrium. contains a unique subset of uterine-specific natural killer (uNK) cells, the proposed functions of which include a role in decidualization, menstruation, and implantation. These cells increase in number during the mid-late secretory phase of the menstrual cycle and are also present in large numbers in early pregnancy. The cyclical nature of uNK cell appearance suggests hormonal regulation of these cells. To date, it has not been possible to localize either estrogen receptors (ERs) or progesterone receptors (PRs) to uNK cells. In the present study, we have investigated the steroid receptor expression of uNK cells, including not only ERalpha and PR but also wild-type ERbeta1, its variant form ERbetacx/beta2, and glucocorticoid receptor (GR) using specific monoclonal antibodies and real-time quantitative RT-PCR. mRNA encoding ERalpha, PR, ERbetacx/beta2, ERbeta1, and GR were identified in extracts of human endometrium across the menstrual cycle and in decidua. Quantitative real-time RT-PCR demonstrated an absence of ERalpha and PR mRNA in purified uNK cells. In contrast, mRNA for ERbetacx/beta2, ERbeta1, and GR was present in uNK cells. ERalpha, PR, ERbetacx/beta2, ERbeta1, and GR proteins were identified in endometrial and decidual biopsies. Colocalization using specific monoclonal antibodies confirmed that uNK cells were immunonegative for ERalpha and PR protein. These cells were also immunonegative for ERbetacx/beta2 but did express ERbeta1 and GR proteins. These results raise the possibility that estrogens and glueocorticoids could be acting directly on uNK cells through ERbeta and GR, respectively, to influence gene transcription in the endometrium and decidua.