Experimental Biology and Medicine >
Volume 227, Number 11 >
Pp. 969-980
MINIREVIEW |
University of Colorado Health Sciences Center, Department of Pathology and Program in Molecular Biology, Denver, Colorado 80262
The effects of progesterone on target tissues are mediated by progesterone receptors (PRs), which belong to a family of nuclear receptors and function as ligand-activated transcription factors to regulate the expression of specific sets of target genes. Progesterone antagonists repress the biological actions of progesterone by "actively" inhibiting PR activation. This work discusses the first clinically used progesterone antagonist RU486 and closely related compounds in terms of how these compounds inhibit progesterone action through heterodimerization and competition for DNA binding and by the recruitment of corepressors to promoters of target genes to repress transcription. We discuss cellular factors that may influence the activity of these compounds, such as the availability of coactivators and corepressors and the context of specific target promoters in any given cell type. We also discuss steroidal and nonsteroidal antagonist selectivity for PR versus other steroid hormone receptors and suggest that it may be possible to develop tissue/cell specific modulators of PR.
Keywords: progesterone, progesterone receptor, steroidal antagonists, RU486, nonsteroidal antagonists
This work was supported by National Institutes of Health grant DK49030 (DPE) and the Individual National Research Service Award DK09662 (SAL).
1 To whom requests for reprints should be addressed at Department of Pathology B216, School of Medicine, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Denver, Colorado 80262. E-mail: Dean.Edwards{at}uchsc.edu
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