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Mechanism of action of progesterone antagonists Leonhardt SA; Edwards DPExp Biol Med (Maywood) 2002[Dec]; 227 (11): 969-80The 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.|Animals[MESH]|Hormone Antagonists/chemistry/*pharmacology[MESH]|Humans[MESH]|Mifepristone/pharmacology[MESH]|Progesterone/*antagonists & inhibitors/metabolism[MESH]|Receptors, Progesterone/*antagonists & inhibitors/chemistry/metabolism[MESH]|Signal Transduction[MESH]|Structure-Activity Relationship[MESH] |
