The Measurement of Maternal Plasma Corticotropin-Releasing Factor (CRF) and CRF-Binding Protein Improves the Early Prediction of Preeclampsia

Abstract

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.

Amniotic Fluid and Umbilical Cord Plasma Corticotropin-Releasing Factor (CRF), CRF-Binding Protein, Adrenocorticotropin, and Cortisol Concentrations in Intraamniotic Infection and Inflammation at Term

“…To date, this is the first study reporting increased concentrations of both CRF and CRF-BP at term gestation because levels of these proteins in amniotic fluid and maternal plasma have been found to be inversely correlated (11,13,22). A possible explanation for the elevated amniotic fluid and umbilical cord plasma CRF-BP concentrations may be found in the genomic characterization of CRF-BP, which has revealed acute phase response elements.…”

“…Whatever the role of CRF-BP, the source of its elevated concentrations in presence of IAI merits further discussion. Indeed, the findings that CRF-BP levels are higher in fetal (12) than maternal plasma (13,22), together with the evidence that stressful events of pregnancy, like parturition, are not associated with changes in placental CRF-BP mRNA expression (31) would suggest that the fetus is the main source of such a neuropeptide and that through its secretion the fetus may protect itself from an overactivation of the HPA axis hormones. …”

Serum markers for predicting pre-eclampsia

“…CRF serum levels were higher while CRF-BP serum levels were lower in pregnant women with hypertensive disorders compared to controls (Perkins et al, 1995;Petraglia et al, 1996). In a prospective, controlled study 58 pregnant women affected by pregnancy induced hypertension were enrolled at 28-29 weeks (Florio et al, 2004). CRF and CRF-BP serum levels were measured and the risk of the development of pre-eclampsia was assessed.…”

Increased expression of miR-325-3p by urocortin 2 and its involvement in stress-induced suppression of LH secretion in rat pituitary

“…CRFbinding protein (CRF-BP), which shows an intermediate affinity to Ucn2, would be proposed as one of factors (12). There has been no study that shows CRF-BP in rat plasma; however, CRF-BP is likely to exist in peripheral blood of rats, because it is synthesized by adrenomedullary chromaffin cells (5) and kupffer cells (4) of rats, and CRF-BP is detected in human peripheral blood (9,19). Therefore, Ucn2 administered intravenously may bind to CRF-BP during peripheral circulation before reaching the gonadotrophs of the pituitary and lose its inhibitory effect on gonadotrophs.…”