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 ER alpha and PR but also wild-type ER beta 1, its variant form ER beta cx/beta 2, and glucocorticoid receptor (GR) using specific monoclonal antibodies and real-time quantitative RT-PCR. mRNA encoding ER alpha, PR, ER beta cx/beta 2, ER beta 1, 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 ER alpha and PR mRNA in purified uNK cells. In contrast, mRNA for ER beta cx/beta 2, ER beta 1, and GR was present in uNK cells. ER alpha, PR, ER beta cx/beta 2, ER beta 1, and GR proteins were identified in endometrial and decidual biopsies. Colocalization using specific monoclonal antibodies confirmed that uNK cells were immunonegative for ER alpha and PR protein. These cells were also immunonegative for ER beta cx/beta 2 but did express ER beta 1 and GR proteins. These results raise the possibility that estrogens and glucocorticoids could be acting directly on uNK cells through ER beta and GR, respectively, to influence gene transcription in the endometrium and decidua.