A proposed mechanism for progesterone regulation of trophoblast MMP2 transcription independent of classical progesterone response elements on its promoter
- 4.1k Downloads
Progesterone receptor act as ligand-inducible transcription factor in the respective target cells by binding to specific progesterone response elements in the promoter of the target genes. However, despite the lack of the classical progesterone response elements on matrix-metalloproteinase-2 promoter, progesterone has been shown to decrease the activity of this promoter
Presentation of the hypothesis
It has recently been suggested that in addition to interacting with their classical co-activators and co-repressors, progesterone receptor are capable of binding to several transcription factors. By interacting with other classes of transcription factors, progesterone receptor is capable of transcriptional activation through the transcription factors cognate DNA binding site.
Testing the hypothesis
Exploring transcription factors and transcription binding sites, interacting with the progesterone receptor in modulation of the matrix-metalloproteinase promoter.
Implications of the hypothesis
Identification of additional endogenous progesterone target genes makes it possible to further explore the signaling mechanisms by which the hormone regulates biological actions. Furthermore, the concepts of ligand-driven conformational diversity and selective tissue actions can be exploited in the future for drug development which selectively regulate orphan receptors from the nuclear receptor family.
- 14.Christian M, Pohnke Y, Kempf R, Gellersen B, Brosens JJ: 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. 2002, 16: 141-154. 10.1210/me.16.1.141.CrossRefPubMedGoogle Scholar
- 15.Zhang XL, Zhang D, Michel FJ, Blum JL, Simmen FA, Simmen RC: Selective interactions of Kruppel-like factor 9/basic transcription element-binding protein with progesterone receptor isoforms A and B determine transcriptional activity of progesterone-responsive genes in endometrial epithelial cells. J Biol Chem. 2003, 278: 21474-21482. 10.1074/jbc.M212098200.CrossRefPubMedGoogle Scholar
- 21.Goldman S, Shalev E: Difference in Progesterone Receptor Isoforms Ratio, Between Early and Late First Trimester Human Trophoblast, Is Associated with Differential Cell Invasion and Matrix Metalloproteinase2 (MMP2) Expression. Biol Reprod. 2006, 74: 13-22. 10.1095/biolreprod.105.044925.CrossRefPubMedGoogle Scholar
- 24.Website title. [http://www.cbil.upenn.edu/tess]
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.