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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 1 440-449
Copyright © 2003 by The Endocrine Society

Original Article

Steroid Receptor Expression in Uterine Natural Killer Cells

Teresa A. Henderson, Philippa T. K. Saunders, Ashley Moffett-King, Nigel P. Groome and Hilary O. D. Critchley

Obstetrics and Gynaecology Section, Department of Reproductive and Developmental Sciences (T.A.H., H.O.D.C.), Medical Research Council Human Reproductive Sciences Unit (P.T.K.S.), Centre for Reproductive Biology, Edinburgh, EH16 4SB, United Kingdom; Department of Pathology (A.M.-K.), University of Cambridge, Cambridge CB2 1QP, United Kingdom; and School of Biological and Molecular Sciences (N.P.G.), Oxford Brookes University, Oxford OX3 0PB, United Kingdom

Address all correspondence and requests for reprints to: Prof. Hilary Critchley, Obstetrics and Gynaecology, Centre for Reproductive Biology, The Chancellor’s Building, The University of Edinburgh Medical School, 49 Little France Crescent, Edinburgh, EH16 4SB, United Kingdom. E-mail: Hilary.Critchley{at}ed.ac.uk.

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 ERß1, its variant form ERßcx/ß2, and glucocorticoid receptor (GR) using specific monoclonal antibodies and real-time quantitative RT-PCR.

mRNA encoding ER{alpha}, PR, ERßcx/ß2, ERß1, 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 ERßcx/ß2, ERß1, and GR was present in uNK cells. ER{alpha}, PR, ERßcx/ß2, ERß1, 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 ERßcx/ß2 but did express ERß1 and GR proteins. These results raise the possibility that estrogens and glucocorticoids could be acting directly on uNK cells through ERß and GR, respectively, to influence gene transcription in the endometrium and decidua.

This work was supported by Medical Research Council Program Grant no. 0000066.

Abbreviations: ER, Estrogen receptor; GR, glucocorticoid receptor; HSD, hydroxysteroid dehydrogenase; NK, natural killer; NRS, normal rabbit serum; PR, progesterone receptor; PRL, prolactin; Q-RT-PCR, quantitative RT-PCR; RT, reverse transcribed; TBS, Tris-buffered saline; uNK, uterine NK; VEGF, vascular endothelial growth factor.




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