Whereas in most mammals the onset of labor is preceded by a rapid fall in the maternal progesterone levels, in humans and in higher primates, maternal, fetal and amniotic fluid concentrations of progesterone are sustained before the onset of labor. Therefore, the mechanism for parturition, which has been proposed for humans, is 'functional' progesterone withdrawal. This review is focused on the expression profile, activity and interaction of the progesterone receptor (PR) isoforms in the decidua and the fetal membrane during the initiation of labor. Binding of progesterone to PR induces a significant conformational change on the receptor proteins. These changes result in dimerization, increased receptor phosphorylation and binding of receptor dimers to specific hormone responsive DNA elements in the promoter of target genes. Interaction with specific co-activator proteins and general transcription factors are responsible for the formation of a productive transcription initiation complex.

The PR also mediates the activation of cytoplasmic signaling pathways, participating in the induction of signal transduction pathway in the cytoplasm. Balanced expression of the two major progesterone receptors isoforms is crucial for progesterone function as uterine muscle inhibitor. Change in PR isoforms profile seems to be responsible for decidual activation. Decidua without contractions shows consistent profile with PR-B being the dominant isoform. PR-A, PR-C and two additional truncated isoforms are also detected but in significantly smaller concentration. After initiation of contractions, a sharp decline in PR-B shifts the PR-A/PR-B ratio toward PR-A dominance. This shift in the decidua towards increase expression of progesterone receptor isoform A and decrease in PR isoform B is having a pivotal role in decidual activation and initiation of labor.