Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
J Steroid Biochem Mol Biol. 2022 Nov;224:106160. doi: 10.1016/j.jsbmb.2022.106160. Epub 2022 Aug 3.
Myometrial contraction is stringently controlled throughout pregnancy and parturition. Progesterone signaling, effecting through the progesterone receptor (PR), is pivotal in modulating uterine activity. Evidence has shown that two major PR isoforms, PR-A and PR-B, have distinct activities on gene regulation, and the ratio between these isoforms determines the contractility of the myometrium at different gestational stages. Herein, we focus on the regulation of PR activity in the myometrium, especially the differential actions of the two PR isoforms, which maintain uterine quiescence during pregnancy and regulate the switch to a contractile state at the onset of labor. To demonstrate the PR regulatory network and its mechanisms of actions on myometrial activity, we summarized the findings into three parts: Regulation of PR Expression and Isoform Levels, Progesterone Receptor Interacting Factors, and Biological Processes Regulated by Myometrial Progesterone Receptor Isoforms. Recent genomic and epigenomic data, from human specimens and mouse models, are recruited to support the existing knowledge and offer new insights and future directions in myometrial biology.
子宫肌层收缩在整个妊娠和分娩过程中受到严格控制。孕激素信号通过孕激素受体(PR)发挥作用,对调节子宫活动至关重要。有证据表明,两种主要的 PR 异构体 PR-A 和 PR-B,对基因调控具有不同的活性,而这些异构体之间的比例决定了不同妊娠阶段子宫肌层的收缩性。本文重点关注 PR 在子宫肌层中的活性调节,特别是两种 PR 异构体的差异作用,它们在妊娠期间维持子宫静止,并在分娩开始时调节向收缩状态的转变。为了阐明 PR 调节网络及其对子宫肌层活动的作用机制,我们将研究结果总结为三个部分:PR 表达和异构体水平的调节、PR 相互作用因子以及受子宫孕激素受体异构体调节的生物学过程。最近从人类标本和小鼠模型中获得的基因组和表观基因组数据,支持了现有的知识,并为子宫生物学提供了新的见解和未来的方向。