Progesterone receptors in the human pregnancy uterus: do they hold the key to birth timing?

The process and timing of human parturition involves a complex hormonal dialogue between maternal and fetal systems that transforms the uterine muscle into the laboring state. Progesterone, through specific progesterone receptors (PRs) in uterine tissues, is key player in this process. For most of pregnancy, progesterone promotes myometrial relaxation and its withdrawal initiates parturition. In women, a functional progesterone withdrawal occurs by changes in PR isoform expression and/or function in myometrial cells. Research in the last 10 to 20 years has shown that progesterone actions are mediated by a variety of PRs including the classic nuclear PRs, PR-A and PR-B that mediate genomic actions, and a family of membrane-bound PRs that mediate non-genomic actions. Herein, we review current understanding of the PRs expressed in the human pregnancy uterus, the pathways through which they mediate progesterone actions, and their roles in controlling myometrial contractility and the parturition process.