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Original Studies |
Westmead Institute for Cancer Research, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia
Address all correspondence and requests for reprints to: Patricia A. Mote, Westmead Institute for Cancer Research, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia. e-mail: patm@westgate.wh.usyd.edu.au.
The human progesterone receptor (PR) is expressed as two isoforms, PRA and PRB, that function as ligand-activated transcription factors. In vitro studies suggest that the isoforms differ functionally and that the relative levels in a target cell may determine the nature and magnitude of response to progesterone. However, it is not known whether the two isoforms are normally coexpressed in vivo. To understand the functional significance of relative PR isoform expression in normal physiology, it is essential to determine whether PRA and PRB are coexpressed in the same cell. This study reports the development of a dual immunofluorescent staining technique to demonstrate PRA and PRB proteins by single cell analysis in the same tissue section of human endometrium during the menstrual cycle. PRA and PRB are coexpressed in target cells of the human uterus. In the glands, PRA and PRB were expressed before subnuclear vacuole formation and glycogenolysis, implicating both isoforms in this process, whereas persistence of PRB during the midsecretory phase suggested its significance in glandular secretion. In the stroma, the predominance of PRA throughout the cycle implicates this isoform in postovulatory progesterone-mediated events. These results support the view that PRA and PRB mediate distinct pathways of progesterone action in the glandular epithelium and stroma of the human uterus throughout the menstrual cycle.
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J. K. Richer, B. M. Jacobsen, N. G. Manning, M. G. Abel, D. M. Wolf, and K. B. Horwitz Differential Gene Regulation by the Two Progesterone Receptor Isoforms in Human Breast Cancer Cells J. Biol. Chem., February 8, 2002; 277(7): 5209 - 5218. [Abstract] [Full Text] [PDF] |
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M. Christian, Y. Pohnke, R. Kempf, B. Gellersen, and J. J. Brosens Functional Association of PR and CCAAT/Enhancer-Binding Protein {beta} Isoforms: Promoter-Dependent Cooperation between PR-B and Liver-Enriched Inhibitory Protein, or Liver-Enriched Activatory Protein and PR-A in Human Endometrial Stromal Cells Mol. Endocrinol., January 1, 2002; 16(1): 141 - 154. [Abstract] [Full Text] [PDF] |
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L. Tung, T. Shen, M. G. Abel, R. L. Powell, G. S. Takimoto, C. A. Sartorius, and K. B. Horwitz Mapping the Unique Activation Function 3 in the Progesterone B-receptor Upstream Segment. TWO LXXLL MOTIFS AND A TRYPTOPHAN RESIDUE ARE REQUIRED FOR ACTIVITY J. Biol. Chem., October 19, 2001; 276(43): 39843 - 39851. [Abstract] [Full Text] [PDF] |
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K. B. C. Apparao, M. J. Murray, M. A. Fritz, W. R. Meyer, A. F. Chambers, P. R. Truong, and B. A. Lessey Osteopontin and Its Receptor {alpha}v{beta}3 Integrin Are Coexpressed in the Human Endometrium during the Menstrual Cycle But Regulated Differentially J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4991 - 5000. [Abstract] [Full Text] [PDF] |
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P A Mote, J F Johnston, T Manninen, P Tuohimaa, and C L Clarke Detection of progesterone receptor forms A and B by immunohistochemical analysis J. Clin. Pathol., August 1, 2001; 54(8): 624 - 630. [Abstract] [Full Text] [PDF] |
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R. L. Arnett-Mansfield, A. deFazio, G. V. Wain, R. C. Jaworski, K. Byth, P. A. Mote, and C. L. Clarke Relative Expression of Progesterone Receptors A and B in Endometrioid Cancers of the Endometrium Cancer Res., June 1, 2001; 61(11): 4576 - 4582. [Abstract] [Full Text] [PDF] |
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T. Suzuki, A. D. Darnel, J.-I. Akahira, N. Ariga, S. Ogawa, C. Kaneko, J. Takeyama, T. Moriya, and H. Sasano 5{{alpha}}-Reductases in Human Breast Carcinoma: Possible Modulator of in Situ Androgenic Actions J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2250 - 2257. [Abstract] [Full Text] |
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M. Sasaki, A. Dharia, B. R. Oh, Y. Tanaka, S.-i. Fujimoto, and R. Dahiya Progesterone Receptor B Gene Inactivation and CpG Hypermethylation in Human Uterine Endometrial Cancer Cancer Res., January 1, 2001; 61(1): 97 - 102. [Abstract] [Full Text] |
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J. Gao, J. Mazella, M. Tang, and L. Tseng Ligand-Activated Progesterone Receptor Isoform hPR-A Is a Stronger Transactivator Than hPR-B for the Expression of IGFBP-1 (Insulin-Like Growth Factor Binding Protein-1) in Human Endometrial Stromal Cells Mol. Endocrinol., December 1, 2000; 14(12): 1954 - 1961. [Abstract] [Full Text] |
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J. Kitawaki, H. Koshiba, H. Ishihara, I. Kusuki, K. Tsukamoto, and H. Honjo Progesterone Induction of 17{beta}-Hydroxysteroid Dehydrogenase Type 2 during the Secretory Phase Occurs in the Endometrium of Estrogen-Dependent Benign Diseases But Not in Normal Endometrium J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3292 - 3296. [Abstract] [Full Text] |
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G. R. ATTIA, K. ZEITOUN, D. EDWARDS, A. JOHNS, B. R. CARR, and S. E. BULUN Progesterone Receptor Isoform A But Not B Is Expressed in Endometriosis J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2897 - 2902. [Abstract] [Full Text] |
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