The role of CRH receptors and their agonists in myometrial contractility and quiescence during pregnancy and labour

Abstract

The mechanism of human labor remains a scientific enigma. Corticotropin-releasing hormone (CRH), a hypothalamic peptide that controls the response of the body to stress and which is also produced by the placenta and intrauterine tissues during pregnancy is potentially involved in the onset of labor. CRH is part of a family of mammalian peptides that includes the urocortins (UCNs), which are also expressed by the placenta and intrauterine tissues. During human pregnancy, CRH appears to target multiple feto-maternal tissues, including the myometrium, implicating CRH in the regulation of the transition from relaxation to active uterine contractions. The myometrial actions of CRH are mediated via a wide network of specific G-protein coupled membrane-bound receptors. These receptors have various functional properties, depending on the receptor subtype, the ability of agonists to activate specific signalling cascades and the stage of pregnancy. In addition, their function is dependant upon other intracellular signals via communication between signalling cascades, suggesting potential multiple roles of CRH and other CRH-like peptides during pregnancy and labor. This review will provide the current concepts about the role of CRH and UCNs and their myometrial receptors during pregnancy, labor and delivery.