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Corticotrophin-releasing hormone and CRH-binding protein. Differences between patients at risk for preterm birth and
C J Hobel1, C P Arora, L M Korst
1Department of Obstetrics and Gynecology, Cedars Sinai Medical Center, Burns and Allen Research Institute, Los Angeles, California 90048, USA. HobelC@CSHS.org
Insights
Elevated corticotropin-releasing hormone (CRH) and lower CRH-binding protein (CRH-BP) are linked to preterm birth (PTB). These hormonal differences suggest excessive CRH may contribute to the timing of delivery in at-risk pregnancies.
Area of Science:
- Reproductive endocrinology
- Maternal-fetal medicine
- Biochemistry
Background:
- Plasma corticotropin-releasing hormone (CRH) rises during pregnancy, primarily from the placenta.
- CRH-binding protein (CRH-BP) inactivates CRH, potentially limiting its peripheral effects.
- Decreased CRH-BP in late pregnancy increases free CRH, possibly initiating parturition.
Purpose of the Study:
- To investigate if CRH, CRH-BP, or CRH/CRH-BP complexes differ in patients at risk for preterm birth (PTB) or hypertension (HYP).
- To determine if these hormonal differences explain variations in parturition timing.
Main Methods:
- Maternal plasma samples were collected from 18 PTB, 23 HYP, and control patients at 18-20, 28-30, and 35-36 weeks of gestation.
- CRH and CRH-BP levels were quantified using radioimmunoassay and immunoradiometric techniques, respectively.
- A CRH-BP/CRH dimer complex index was calculated, and data analyzed using the Kruskal-Wallis test.
Main Results:
- Significantly elevated maternal CRH levels were observed in PTB cases compared to HYP and control groups at all time points.
- Maternal CRH-BP levels were significantly lower in PTB cases versus HYP and control groups throughout gestation.
- The CRH-BP/CRH dimer complex index was significantly reduced in PTB cases, indicating excessive free CRH.
Conclusions:
- Patients at risk for PTB exhibit elevated CRH and reduced CRH-BP levels.
- A lower CRH-BP/CRH dimer complex index in PTB patients suggests an imbalance favoring free CRH.
- These hormonal profiles may be critical factors in the onset of preterm labor.
Background:
During pregnancy in the second and third trimester there is a progressive rise in plasma CRH thought to be secreted by the placenta. Plasma CRH-BP inactivates CRH, which may prevent its peripheral action on the maternal pituitary and myometrium. In the last few weeks of pregnancy CRH-BP decreases, thereby causing an increase in free CRH or a CRH/CRH-BP complex available to play a role in the onset of parturition.
Objective:
We tested the hypothesis that differences in CRH, CRH-BP, or a CRH/CRH-BP complex in patients at risk for preterm birth (PTB) and hypertension (HYP) account for the differences in the timing of parturition.
Methods:
From a Behavior in Pregnancy Study database, we identified 18 patients who had spontaneous PTB and 23 patients who developed HYP. Both groups were case controlled and matched with patients who delivered at term (Normal). Maternal plasma samples had been appropriately collected from these patients at 18-20, 28-30, and 35-36 weeks gestational age. CRH levels were measured by double antibody RIA kit and the CRH-BP by a immunoradiometric technique. A CRH-BP/CRH dimer complex index was calculated. Statistical analysis was done using Kruskal-Wallis test for two cases.
Results:
Maternal CRH (pg/ml) in the PTB cases compared to the HYP cases was significantly elevated at all three time periods. Maternal CRH-BP (pg/ml) in the PTB versus HYP cases was significantly lower at all three time periods in the PTB cases compared to the HYP cases. Maternal CRH-BP/CRH dimer complex index was significantly lower in the PTB cases at all three time periods than either the controls or the HYP cases, suggesting excessive CRH. The mean GA at delivery for the PTB cases was significantly lower than the control or HYP cases.
Conclusions:
These results suggest that those patients at risk for PTB have significantly elevated CRH, lower CRH-BP, and a reduced CRH-BP/CRH dimer complex index at all three time periods of assessment.