Placental corticotrophin-releasing hormone and its receptors in human pregnancy and labour: still a scientific enigma.

It is now accepted that, in humans, placental corticotrophin-releasing hormone (CRH) is involved in the mechanisms controlling the onset of labour; however, the precise biological role in foeto-maternal tissues remain enigmatic. Maternal plasma levels of CRH rise exponentially as pregnancy progresses towards term and peak during labour; however, evidence to link this with an active role in the onset and progression of labour, is still inconclusive. Certainly, one of the tissues targeted by CRH is the myometrial smooth muscle, which expresses a plethora of specific CRH receptors. This finding implicates CRH in the mechanisms preparing the myometrial microenvironment for the onset of labour and possibly in the regulation of active contractility during labour. Other gestational tissues also targeted by CRH include the placenta, foetal membranes and foetal adrenals, where CRH might regulate distinct physiological functions, ranging from control of vascular tone to adrenal steroidogenesis and prostaglandin synthesis and activity. Given the unique, among mammals, pattern of human placental CRH secretion and CRH receptor expression and signalling during pregnancy and labour, there are only limited biological tools available to delineate the actions of CRH in foeto-maternal tissues, primarily based on in vitro characterisation of the signalling and molecular events driven by CRH. This review will set in context the current concepts about the role of CRH and its receptors during pregnancy and labour, focusing on the unresolved questions and paradoxes that currently exist.