Leonhardt Susan A, Edwards Dean P
University of Colorado Health Sciences Center, Department of Pathology, Denver, Colorado 80262, USA.
Exp Biol Med (Maywood). 2002 Dec;227(11):969-80. doi: 10.1177/153537020222701104.
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.
孕酮对靶组织的作用是由孕酮受体（PRs）介导的，孕酮受体属于核受体家族，作为配体激活的转录因子发挥作用，以调节特定靶基因集的表达。孕酮拮抗剂通过“主动”抑制PR激活来抑制孕酮的生物学作用。本文讨论了首个临床使用的孕酮拮抗剂RU486以及与之密切相关的化合物，涉及这些化合物如何通过异二聚化和竞争DNA结合，以及通过招募共抑制因子至靶基因启动子来抑制转录，从而抑制孕酮作用。我们讨论了可能影响这些化合物活性的细胞因子，如共激活因子和共抑制因子的可用性，以及任何给定细胞类型中特定靶启动子的背景。我们还讨论了PR与其他类固醇激素受体相比，甾体和非甾体拮抗剂的选择性，并表明有可能开发PR的组织/细胞特异性调节剂。
