Immune Aspects and Myometrial Actions of Progesterone and CRH in Labor

Figure 1

Mechanisms of functional progesterone withdrawal for the initiation of parturition. Progesterone binds to its nuclear receptor PR and activates genomic pathways that maintain uterine quiescence. Functional progesterone withdrawal occurs through many mechanisms: (a) the expression of different PR isoforms (increased PR-A:PR-B ratio and the expression of PR-C), (b) the decreased expression of PR coactivators, such as CBP, SRC-2, SRC-3, (c) binding of progesterone to membrane progesterone receptors (mPR) which activate nongenomic pathways, and (d) immune factors such as cytokines and chemokines activating NF-κB, that in turn lead to functional progesterone withdrawal. NF-κB increases the expression of COX-2 and contractile genes. Progesterone withdrawal together with increased expression of COX-2 and contractile genes results in increased myometrial contractions, which is a vital component for the initiation of labor. PR: progesterone receptor, CBP: CREB-binding protein, SRC: steroid receptor coactivators, NF-κB: nuclear factor kappa-light-chain enhancer of activated B cells, mPRs: membrane progesterone receptors, COX-2: cyclooxygenase-2.