Abstract
BackgroundProgesterone 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 promoterPresentation of the hypothesisIt 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 hypothesisExploring transcription factors and transcription binding sites, interacting with the progesterone receptor in modulation of the matrix-metalloproteinase promoter.Implications of the hypothesisIdentification 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.
Highlights
progesterone receptor (PR) acts as ligand-inducible transcription factor in the respective target cell by binding to specific progesterone response elements (PRE) in the promoter of target genes
The presence of the AF-3 domain in the PR-B, and its lack in other isoforms is likely to be responsible for the differential transactivation properties that contribute to the complete repertoire of physiological responses to progesterone [6,7,8]
We suggest that in such cases progesterone serves as co-activator or co-repressor
Summary
The physiological effects of progesterone are classically mediated by interaction of the hormone with the two classical intracellular progesterone receptor (PR) isoforms PRA and PR-B [1]. Binding to consensus PRE may not necessarily be required for P-responsiveness of target genes These dual mechanisms enable the differential role of each receptor in the transcriptional regulation of specific gene either by direct binding or by interaction with specific transcription factors to specific binding regions in the promoter. Specific aim 2: Identification of transcription binding sites and transcription factors involved in progesterone modulation: relative roles of progesterone receptor isoforms Specific Aim 1 will provide a physical determination of the site(s) present in the MMP promoter that regulate the transcriptional response to progesterone. We will screen these sites for potential transcription factors with the TransFac/TESS databases (24). The concepts of ligand-driven conformational diversity and selective tissue actions can be exploited in the future for drug development that will selectively regulate orphan receptors from the nuclear receptor family
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of Experimental & Clinical Assisted Reproduction
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
