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Institute of Reproductive and Developmental Biology, Wolfson & Weston Research Centre for Family Health, Imperial College London, Hammersmith Hospital, London W12 0NN, UK
1 Inpharmatica Ltd, London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UK
2 Biomedical Research Institute, Department of Biological Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
3 Cancer Research-UK Labs and Section of Cancer Cell Biology, Department of Cancer Medicine, Imperial College London, Hammersmith Hospital, London W12 0NN, UK
4 Endokrinologikum Hamburg, Falkenried 88, 20251 Hamburg, Germany
(Requests for offprints should be addressed to J Brosens; Email: j.brosens{at}imperial.ac.uk)
Rapid non-genomic actions of progesterone are implicated in many aspects of female reproduction. Recently, three human homologues of the fish membrane progestin receptor (mPR) have been identified. We combined bioinformatic analysis with expression profiling to define further the role of these mPRs in human reproductive tissues. Sequence analysis confirmed that the mPRs belong to a larger, highly conserved family of proteins, termed ‘progestin and adiponectin receptors’ (PAQRs). A comparison of the expression of mPR transcripts with that of two related PAQR family members, PAQRIII and PAQRIX, in cycling endometrium and pregnancy tissues revealed markedly divergent expression levels and profiles. For instance, endometrial expression of mPR
and 
and PAQRIX was cycle-dependent whereas the onset of parturition was associated with a marked reduction in myometrial mPR and ß transcripts. Interestingly, mPR and PAQRIX were most highly expressed in the placenta, and the tissue expression levels of both genes correlated inversely with that of the nuclear PR. Phylogenetic analysis demonstrated that PAQRIX belongs to the mPR subgroup of proteins. We also validated a polyclonal antibody raised against the carboxy-terminus of human mPR. Immunohistochemical analysis demonstrated more intense immunoreactivity in placental syncytiotrophoblasts than in endometrial glands or stroma. The data suggest important functional roles for mPR, and possibly PAQRIX, in specific reproductive tissues, particularly those that express low levels of nuclear PR.
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