Endocrine Abstracts

In most species progesterone acts to inhibit cervical ripening and myometrial contractility throughout pregnancy and labour is heralded by prostaglandin stimulated withdrawal of progesterone. Human labour is associated with increased prostaglandin synthesis, via COX-2 but there is no clear systemic withdrawal of progesterone at the time of labour. There is upregulation of genes which are normally repressed by progesterone leading to the concept that human labour is associated with 'functional progesterone withdrawal'. Several, not mutually exclusive, mechanisms may explain this. There is a change in the expression pattern of progesterone receptors at the time of labour, with an increase in expression of PR-A in myometrium. In myometrium PR-A represses the transcriptional activity of PR-B. In the amnion labour there is increased activity of the NF-kappa B transcription factor system involving the classical proteins p50 and p65. This appears to be permanent and is mediated, not through the usual degradation of the inhibitory IkBalpha protein, but through increased expression of the related IkBbeta protein which acts to protect NF-kappa B from inhibition by newly synthesized IkBalpha. Increased NF-kappa B activity leads to an increase in expression of COX-2, of inflammatory cytokines such as IL-8 and IL1b which cause ripening of the cervix and of the oxytocin receptor. There is a mutually negative interaction between NF-kappa B (p65) and PR which functions in amnion, such that, as p65 expression increases PR is repressed. There also appears to be an increase in NF-kappa B activity in myometrium with labour. Therefore, although at first sight the biochemistry of labour in humans appears to be very different to that in other species, in fact, there is a common template. Increased prostaglandin synthesis through COX-2 and changes in progesterone function are linked leading to similar changes in the expression of a series of 'labour associated proteins'.