Journal of the Society for Gynecologic Investigation

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

http://mc.manuscriptcentral.com/rsci

Click here to sign up for SAGE Journal Email Alerts today!

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text (PDF)
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Edwards, D. P.
Right arrow Articles by Gass-Handel, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Edwards, D. P.
Right arrow Articles by Leonhardt, S. A.
Right arrow Articles by Gass-Handel, E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Journal of the Society for Gynecologic Investigation, Vol. 7, No. 1 suppl, S22-S24 (2000)
DOI: 10.1177/107155760000700108

Novel Mechanisms of Progesterone Antagonists and Progesterone Receptor

Dean P. Edwards, PhD

Department of Pathology, University of Colorado Health Sciences Center, 4200 East 9 Avenue, Denver, CO 80262-0001

Susan A. Leonhardt, PhD

Elizabeth Gass-Handel, PhD

Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado

The progesterone receptor (PR), as a member of the nuclear receptor superfamily of ligand-dependent transcription factors, activates gene transcription through binding to specific palindromic progesterone response elements (PRE) in the promoter region of progestin-responsive genes. The progesterone antagonists ZK98299 (Onapristone) and RU 486 (Mifepristone) inhibit the transcriptional activity of PR by complex mechanisms at concentrations much lower than the progestins. Altered conformation is central to antagonist inhibition of the transcriptional activity of PR. Antagonists also promote inappropriate association of PR with corepressors. We speculate that the different PR conformations induced by agonist and antagonists results in an asymmetric agonist/antagonist heterodimer that binds inefficiently to palindromic PREs. PR, under the same cellular conditions but with different promotor contexts, can repress (ß-casein) or enhance (3ß-HSD) signal transducer and activator of transcription (Stat5)-mediated gene activation. The ß-casein promoter appears to contain a composite DNA-binding element for PR and Stat5 and that occupancy by PR in response to progestins or antagonists suppresses Stat5 transactivation function.

Key Words: Progesterone antagonist • progesterone receptor • corepressor • ß-casein • Stat5


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?