The complex mechanisms controlling human parturition involves mother, fetus, and placenta, and stress is a key element activating a series of physiological adaptive responses. Preterm birth is a clinical syndrome that shares several characteristics with term birth. A major role for the neuroendocrine mechanisms has been proposed, and placenta/membranes are sources for neurohormones and peptides. Oxytocin (OT) is the neurohormone whose major target is uterine contractility and placenta represents a novel source that contributes to the mechanisms of parturition. The CRH/urocortin (Ucn) family is another important neuroendocrine pathway involved in term and preterm birth. The CRH/Ucn family consists of four ligands: CRH, Ucn, Ucn2, and Ucn3. These peptides have a pleyotropic function and are expressed by human placenta and fetal membranes. Uterine contractility, blood vessel tone, and immune function are influenced by CRH/Ucns during pregnancy and undergo major changes at parturition. Among the others, neurohormones, relaxin, parathyroid hormone-related protein, opioids, neurosteroids, and monoamines are expressed and secreted from placental tissues at parturition. Preterm birth is the consequence of a premature and sustained activation of endocrine and immune responses. A preterm birth evidence for a premature activation of OT secretion as well as increased maternal plasma CRH levels suggests a pathogenic role of these neurohormones. A decrease of maternal serum CRH-binding protein is a concurrent event. At midgestation, placental hypersecretion of CRH or Ucn has been proposed as a predictive marker of subsequent preterm delivery. While placenta represents the major source for CRH, fetus abundantly secretes Ucn and adrenal dehydroepiandrosterone in women with preterm birth. The relevant role of neuroendocrine mechanisms in preterm birth is sustained by basic and clinic implications.
Urocortin stimulates IL-4 and IL-10 secretion and reverses LPS-induced TNF-alpha release from trophoblast cells through action on CRH-R2 receptors, suggesting that this peptide may play a possible role as an anti-inflammatory agent.
Maternal plasma urocortin concentration is increased in patients with TPTL who have PTD, and its measurement may be a promising new biochemical marker of PTD.
In the present study we measured maternal plasma concentrations of two placental neurohormones, corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP), in 58 at-risk pregnant women consecutively enrolled between 28 and 29 wk of pregnancy to evaluate whether their evaluation may predict third trimester-onset preeclampsia (PE). The statistical significance was assessed by t test. The cut-off points for defining altered CRF and CRF-BP levels for prediction of PE were chosen by receiving operator characteristics curve analysis, and the probability of developing PE was calculated for several combinations of hormone testing results. CRF and CRF-BP levels were significantly (both P < 0.0001) higher and lower, respectively, in the patients (n = 20) who later developed PE than in those who did not present PE at follow-up. CRF at the cut-off 425.95 pmol/liter achieved a sensitivity of 94.8% and a specificity of 96.9%, whereas CRF-BP at the cut-off 125.8 nmol/liter combined a sensitivity of 92.5% and a specificity of 82.5% as single markers for prediction of PE. The probability of PE was 34.5% in the whole study population, 93.75% when both CRF and CRF-BP levels were changed, and 0% if both hormone markers were unaltered. The measurement of CRF and CRF-BP levels may add significant prognostic information for predicting PE in at-risk pregnant women.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.