Human labour is associated with nuclear factor-kappa B activity which mediates cyclo-oxygenase-2 expression and is involved with the 'functional progesterone withdrawal'

Human labour is associated with the up-regulation of prostaglandins within the uterus, synthesized via the type-2 cyclo-oxygenase enzyme (COX-2), Thes e lead to remodelling of the fetal membranes and cervix and to stimulation of myometrial contractions. In the human, the principal source of prostagla ndins is the amnion, Progesterone acts to promote myometrial quiescence, an d in many species the onset of labour is preceded by withdrawal of progeste rone, Humans show no systemic progesterone withdrawal, although biochemical changes within the uterus are similar to those in other species. A mutual negative interaction between the transcription factor nuclear factor (NF)-k appaB and the progesterone receptor (PR) has been reported. Using transient transfections and assays for transcriptional activation and promoter bindi ng, we have shown that there is constitutive activity of NF-kappaB in amnio n cells at the time of labour, and that COX-2 expression depends upon NF-ka ppaB, In cells obtained before labour, in which NF-kappaB activity is low, increasing the concentration of PR represses NF-kappaB dependent transcript ion, while stimulation with IL-1 beta both increases NF-kappaB activity and represses PR activity. Our data suggest that human labour is associated wi th constitutive NF-kappaB activity within the amnion, which functions to in crease the expression of COX-2 and appears to contribute to the 'functional progesterone withdrawal'.