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Prolactin Induces ERK Phosphorylation in Epithelial and CD56⁺ Natural Killer Cells of the Human Endometrium

Medical Research Council Human Reproductive Sciences Unit (O.G., H.N.J.) and Department of Reproductive and Developmental Sciences (H.O.D.C.), University of Edinburgh, Centre for Reproductive Biology, Edinburgh EH3 9ET, United Kingdom; and Department of Pathology (J.M.B., A.K.), University of Cambridge, Cambridge CB2 1QP, United Kingdom

Address all correspondence and requests for reprints to: Dr. H. N. Jabbour, Medical Research Council Human Reproductive Sciences Unit, Center for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9ET, United Kingdom. E-mail: . h.jabbour{at}hrsu.mrc.ac.uk

Abstract

Functional PRL receptors are expressed in the human endometrium during the secretory phase of the menstrual cycle in which PRL stimulates tyrosine phosphorylation of Janus kinase 2 and STAT (signal transducer and activator of transcription) 1 and 5. In this study, we investigated the effect of PRL on the MAPK/ERK pathway in the human endometrium. Human endometrial tissue was collected during the mid to late secretory phase of the menstrual cycle. Western blot analysis performed on proteins, extracted after up to 30 min culture with PRL, demonstrated rapid tyrosine and threonine phosphorylation of ERK 1 and 2 MAPKs. The phosphorylation of ERK, in response to PRL, was localized by immunohistochemistry to glandular epithelial cells and a subset of stromal cells. Using immunofluorescence histochemistry, PRL-induced phosphorylation of ERK in the stromal compartment was localized to the uterine-specific CD56⁺ natural killer (NK) cells. We have demonstrated that the PRL receptor is expressed in uterine CD56⁺ NK cells in situ by immunofluorescence and in purified decidual CD56⁺ NK cells by RT-PCR and Western blotting analysis. We have further demonstrated phosphorylation of ERK 1 and 2 in cultures of purified uterine CD56⁺ NK cells, in response to PRL. Our data demonstrate that PRL stimulates the ERK pathway in multiple cellular compartments of the human endometrium and identify uterine CD56⁺ NK cells as novel PRL target cells.

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