METHODS: Myometrial strips were obtained from non-pregnant, pregnant, and postpartum rats, and the nongenomic effects of progesterone in the myometrium during pregnancy were examined. Additionally, the influence of actinomycin D and cycloheximide and the effects of Org OD-02-0 (a specific membrane progesterone receptor (mPR) agonist) in the myometrium were investigated. Moreover, DNA microarray and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to identify genes involved in progesterone-induced effects in the myometrium.
RESULTS: Progesterone did not cause rhythmic contractions in non-pregnant myometrium but induced rhythmic contractions in pregnant myometrium, with the effects peaking at 20 d + 8 h of pregnancy. However, myometrial contractions decreased after delivery and were restored to non-pregnant levels at 7 d postpartum. Additionally, progesterone stably inhibited high KCl-induced myometrial contractions during pregnancy. Moreover, the nongenomic effects of progesterone were unaffected by actinomycin D or cycloheximide, and Org OD-02-0 effectively mimicked these effects. DNA microarray analysis and qRT-PCR revealed a significant increase in mPRβ gene expression during pregnancy. However, mPRα, mPRγ, mPRδ, and mPRε expression levels remained unchanged.
CONCLUSIONS: The stimulatory nongenomic effect of progesterone, which was inducible and mPRβ-dependent during pregnancy, may be involved in parturition. The inhibitory effect, which was constitutive and depended on other mPRs, may be involved in pregnancy maintenance.
方法:子宫肌层条取自非孕妇,怀孕,产后老鼠,并检查了孕酮在妊娠期间子宫肌层的非基因组效应。此外,研究了放线菌素D和环己酰亚胺的影响以及OrgOD-02-0(一种特定的膜孕酮受体(mPR)激动剂)在子宫肌层中的作用。此外,进行DNA微阵列和定量实时聚合酶链反应(qRT-PCR)以鉴定参与孕酮诱导的子宫肌层作用的基因。
结果:孕酮不引起非妊娠子宫肌层的节律性收缩,但引起妊娠子宫肌层的节律性收缩,效果在怀孕20d+8h达到峰值。然而,分娩后子宫肌层收缩减少,产后7d恢复到非妊娠水平。此外,孕酮稳定抑制怀孕期间高KCl诱导的子宫肌层收缩。此外,黄体酮的非基因组效应不受放线菌素D或环己酰亚胺的影响,和OrgOD-02-0有效地模仿了这些效果。DNA微阵列分析和qRT-PCR显示,怀孕期间mPRβ基因表达显着增加。然而,mPRα,mPRγ,mPRδ,和mPRε表达水平保持不变。
结论:孕酮的刺激性非基因组效应,在怀孕期间是诱导型和mPRβ依赖性的,可能参与分娩。抑制作用,这是构成性的,并且依赖于其他mPRs,可能参与妊娠维持。