Maternal Corticotropin-releasing Hormone Research Articles

Psychosocial Stressors in Relation to Maternal Plasma Levels of Corticotrophin Releasing Hormone (CRH) During Pregnancy

Background: Psychosocial stress during pregnancy has been associated with a number of adverse birth outcomes, including preterm birth. However, we have a limited understanding of the biologic pathways that might link stress to adverse outcomes. Corticotrophin Releasing Hormone (CRH) may represent one possible mechanism, as elevated levels of CRH have been associated with preterm birth. The purpose of this study was to examine the relationships between maternal self-reported psychosocial stress and CRH during pregnancy. We hypothesized that women who experienced psychosocial stress would have elevated levels of CRH. Methods: Women were enrolled in the Chemicals in Our Bodies-2 cohort (N=496), a demographically diverse cohort of pregnant women in San Francisco. CRH (pg/mL) was measured in plasma obtained at the 2nd trimester visit. Psychosocial stress was assessed via self-reported questionnaire at the 2nd trimester and included dichotomous measures of neighborhood quality, stressful life events, caregiving, discrimination, financial strain, job strain, food insecurity, unplanned pregnancy, perceived stress, depression, and perceived community status. Linear regression was used to examine associations between psychosocial stressors and CRH. Results: Experiencing >2 stressful life events was associated with elevated levels of CRH after adjusting for gestational age at visit, maternal race/ethnicity, maternal education, and marital status (β=0.16, 95% confidence interval [CI]=0.02, 0.31). Women who experienced financial strain (β=0.13, 95% CI=-0.10, 0.36), caregiving for an ill family member (β=0.13, 95% CI=-0.06, 0.32), or who had elevated levels of perceived stress (β=0.20, 95% CI=-0.20, 0.41) also had moderately increased CRH levels. No associations were observed between other psychosocial stressor and CRH levels. Conclusions: We observed a positive association between stressful life events and elevated CRH levels in our study population. Future research should explore the combined effects of psychosocial stress and chemicals on birth outcomes and examine CRH as a mediator of the psychosocial stress and birth outcomes relationships.

Association between Maternal Serum Hormones along the Maternal–Fetal Hypothalamic–Pituitary–Adrenal Axis and Successful Vaginal Delivery Measured Prior to Labor Induction

This study aimed to evaluate if maternal serum hormones along the maternal-fetal hypothalamic-pituitary-adrenal (HPA) axis, when drawn prior to labor induction, differed between women who delivered vaginally and those who underwent cesarean. This was a prospective observational study at a single perinatal center performed from August 2017 to May 2018. Nulliparous women with uncomplicated singleton pregnancies ≥39 weeks had maternal serum collected prior to induction. Corticotrophin-releasing hormone (CRH) was measured by ELISA; dehydroepiandrosterone sulfate (DHEA-S), cortisol, estriol (E3) estradiol (E2), and progesterone (P4) were measured by chemiluminescent reaction. Mean analyte concentrations as well as three ratios (E2/P4, E3/P4, and E2/E3) were compared between women who had a vaginal versus cesarean delivery. Logistic regression was used to model the relationship between CRH and the odds of vaginal birth. We estimated that a sample size of 66 would have 90% power to detect a 25% difference in mean CRH levels assuming a vaginal:cesarean ratio of 2:1 with a baseline CRH concentration of 140 (standard deviation = 36) pg/mL. Of the 88 women who had their serum analyzed, 27 (31%) underwent cesarean. Mean maternal serum CRH levels were similar between the vaginal delivery and cesarean groups (122.6 ± 95.2 vs. 112.3 ± 142.4, p = 0.73). Similarly, there were no significant differences in any other maternal serum analytes or ratios. Logistic regression showed a nonsignificant odds ratio for successful vaginal birth (p = 0.69) even when evaluating only the 16 women who had a cesarean for an arrest disorder (p = 0.08). In low-risk nulliparous women undergoing full-term labor induction, there were no differences noted in a broad array of other maternal-fetal HPA-axis hormones between women who had a vaginal or cesarean delivery.

Transcriptional co-activator TAZ controls extravillous trophoblast formation and function in the developing human placenta

The most adverse perinatal outcome of intrahepatic cholestasis of pregnancy (ICP) is sudden fetal death related to acute fetoplacental hypoxia. Corticotrophin-releasing hormone (CRH), urocortin (UCN), and Wolfram syndrome 1 (WFS1) proteins may have a compensatory response to hypoxic stress.A total of 108 singleton pregnant women were divided into three groups: control, late-onset ICP, and early-onset ICP. Enzyme-linked immunosorbent assays were used to detected maternal serum CRH, UCN, and WFS1 levels. Western blotting and real-time polymerase chain reaction were conducted to quantify placental protein and mRNA levels of CRH, UCN, and WFS1. Pearson correlation scatterplots and Pearson correlation matrix were employed to testify the correlation.Placental WFS1 had a positive relation with placental UCN (r = 0.69, P < 0.05) and serum UCN (r = 0.36, P < 0.05). Placental CRH was positively correlated with maternal serum CRH (r = 0.53, P < 0.05). Maternal serum and placental levels of CRH, UCN, and WFS1 significantly increased in the early-onset ICP group compared with the control group (P < 0.05). Placental levels of UCN and WFS1 in the early-onset ICP group were significantly elevated and higher in comparison with the late-onset ICP group (P < 0.05). However, the transcriptional levels of CRH, UCN, and WFS1 were impaired in the early-onset ICP group.Our study revealed that transcription and translation of WFS1, CRH, and UCN were altered during pregnancies complicated by early-onset ICP. This disrupted compensatory response mediated by WFS1 and CRH family peptides in early-onset ICP may play a significant role in the pathogenesis of sudden fetal death in acute fetal hypoxia.

Pericytes mapping in bovine placenta

The most adverse perinatal outcome of intrahepatic cholestasis of pregnancy (ICP) is sudden fetal death related to acute fetoplacental hypoxia. Corticotrophin-releasing hormone (CRH), urocortin (UCN), and Wolfram syndrome 1 (WFS1) proteins may have a compensatory response to hypoxic stress.A total of 108 singleton pregnant women were divided into three groups: control, late-onset ICP, and early-onset ICP. Enzyme-linked immunosorbent assays were used to detected maternal serum CRH, UCN, and WFS1 levels. Western blotting and real-time polymerase chain reaction were conducted to quantify placental protein and mRNA levels of CRH, UCN, and WFS1. Pearson correlation scatterplots and Pearson correlation matrix were employed to testify the correlation.Placental WFS1 had a positive relation with placental UCN (r = 0.69, P < 0.05) and serum UCN (r = 0.36, P < 0.05). Placental CRH was positively correlated with maternal serum CRH (r = 0.53, P < 0.05). Maternal serum and placental levels of CRH, UCN, and WFS1 significantly increased in the early-onset ICP group compared with the control group (P < 0.05). Placental levels of UCN and WFS1 in the early-onset ICP group were significantly elevated and higher in comparison with the late-onset ICP group (P < 0.05). However, the transcriptional levels of CRH, UCN, and WFS1 were impaired in the early-onset ICP group.Our study revealed that transcription and translation of WFS1, CRH, and UCN were altered during pregnancies complicated by early-onset ICP. This disrupted compensatory response mediated by WFS1 and CRH family peptides in early-onset ICP may play a significant role in the pathogenesis of sudden fetal death in acute fetal hypoxia.

Disrupted compensatory response mediated by Wolfram syndrome 1 protein and corticotrophin-releasing hormone family peptides in early-onset intrahepatic cholestasis pregnancy

IntroductionThe most adverse perinatal outcome of intrahepatic cholestasis of pregnancy (ICP) is sudden fetal death related to acute fetoplacental hypoxia. Corticotrophin-releasing hormone (CRH), urocortin (UCN), and Wolfram syndrome 1 (WFS1) proteins may have a compensatory response to hypoxic stress. MethodsA total of 108 singleton pregnant women were divided into three groups: control, late-onset ICP, and early-onset ICP. Enzyme-linked immunosorbent assays were used to detected maternal serum CRH, UCN, and WFS1 levels. Western blotting and real-time polymerase chain reaction were conducted to quantify placental protein and mRNA levels of CRH, UCN, and WFS1. Pearson correlation scatterplots and Pearson correlation matrix were employed to testify the correlation. ResultsPlacental WFS1 had a positive relation with placental UCN (r = 0.69, P < 0.05) and serum UCN (r = 0.36, P < 0.05). Placental CRH was positively correlated with maternal serum CRH (r = 0.53, P < 0.05). Maternal serum and placental levels of CRH, UCN, and WFS1 significantly increased in the early-onset ICP group compared with the control group (P < 0.05). Placental levels of UCN and WFS1 in the early-onset ICP group were significantly elevated and higher in comparison with the late-onset ICP group (P < 0.05). However, the transcriptional levels of CRH, UCN, and WFS1 were impaired in the early-onset ICP group. DiscussionOur study revealed that transcription and translation of WFS1, CRH, and UCN were altered during pregnancies complicated by early-onset ICP. This disrupted compensatory response mediated by WFS1 and CRH family peptides in early-onset ICP may play a significant role in the pathogenesis of sudden fetal death in acute fetal hypoxia.

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva.

Background:Corticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.Methods:We investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children’s blood cells collected at mid-childhood (N = 239, age: 6.7–10.3 years) additionally adjusting for the children’s age at blood drawn.Results:Maternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate < 0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).Conclusion:In our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood.

In pregnancy increased maternal STAI trait stress score shows decreased insulin sensitivity and increased stress hormones

IntroductionChronic or acute stressors influence maternal and fetal Hypothalamus-Pituitary-Adrenal Axes (HPA) during pregnancy. In this study, the effect of maternal stress into maternal insulin sensitivity was investigated during pregnancy. Materials and methodsEighty-two pregnant women [aged 27.1±2.5 (mean±SD) yrs; BMI=25±2.2kg/m2] had at the 2nd and 3rd trimesters anthropometry, fasting blood samples (cortisol, Corticotropin Releasing Hormone (CRH), active amylin, Interleukin (IL6)), Oral Glucose Tolerance Test (OGTT) for glucose and insulin, state-trait anxiety inventory (STAI) trait and state questionnaires (for stress assessment). ResultsMaternal cortisol, CRH and STAI state score increased significantly from 2nd to 3rd trimester. At these trimesters women with STAI trait scores ≥40 had greater serum cortisol and CRH concentrations and lower insulin sensitivity index (ISI) values than those with scores <40 while STAI trait score predicted negatively ISI. At the 2nd trimester maternal CRH concentrations correlated positively with maternal STAI state, Homeostatic Model Assessment Insulin Resistance (HOMAR), 1st and 2nd phase insulin secretion and negatively with ISI. STAI trait correlated negatively with ISI. STAI state correlated positively with maternal systolic blood pressure and HOMAR. At the 3rd trimester STAI trait correlated negatively and positively with ISI and STAI state, respectively, while STAI state correlated positively with HOMAR. In women with STAI state scores ≥40, these scores correlated positively with maternal CRH. ConclusionsIn normal pregnant women, enhanced long-term stress is associated with decreased insulin sensitivity. Both long- and short- term stress are associated with enhanced maternal HPA axis and increased placental CRH secretion.

Additive effects of maternal depressive symptoms during pregnancy and three years after childbirth on offspring psychiatric symptoms in early childhood

Introduction: Themechanisms underlying the effects ofmaternal prenatal stress on foetal development remain elusive. One hypothesis is that maternal stress leads to increased cortisol blood concentrations, which in turn may overstimulate the secretion of placental corticotropin releasing hormone (CRH) into the foetal circulation. However, whether acute stress-induced rises in maternal cortisol affect foeto-placental CRH levels is unknown. We therefore aimed at exploring the association between the acutematernal psychobiological stress response as well as chronic maternal stress perception and foeto-placental CRH levels. Methods: We examined thirty-four healthy pregnant women (37.4±4.0 years) undergoing second-trimester amniocentesis. The amniocentesis served as a naturalistic stress situationduringwhich we repeatedly obtained questionnaires on maternal acute stress perception and saliva samples for cortisol analysis. We furthermore monitored maternal cardiac activity continuously (i.e., heart rate, heart rate variability). Thewomen also responded to the social overload scale of the Trier Inventory of Chronic Stress (Schultz and Schlotz, 1999). CRH levels were analysed from an amniotic fluid aliquot. Results: The amniocentesis induced significant changes in maternal stress perception, salivary cortisol, and cardiac activity. No significant association between the acute psychobiological stress response and amniotic CRH was apparent (all p> .10). However, maternal chronic social overload was positively correlated with CRH levels (Kendall’s tau= .34, p= .02). Conclusions: The current findings provide evidence thatmaternal chronic stress affects placental CRH secretion. However, we cannot exclude that a different or longer timeframe might be required to detect an association between acute maternal stress and foeto-placental CRH. Further studies are called for.

Corticotropin-releasing hormone expression in patients with intrahepatic cholestasis of pregnancy after ursodeoxycholic acid treatment: an initial experience

Objective:Corticotropin-releasing hormone (CRH) is one of the most potent vasodilatory factors in the human feto-placental circulation. The expression of CRH was significantly down-regulated in patients with intrahepatic cholestasis of pregnancy (ICP).Methods:One hundred pregnant women diagnosed with ICP at 34–34+6 weeks of gestation agreed to participate in this prospective nested case–control study. Thirty ICP patients were finally recruited in this study, with 16 cases in the ursodeoxycholic acid (UDCA) group (UDCA 750 mg/d) and 14 cases in the control group (Transmetil 1000 mg/d or Essentiale 1368 mg/d). Maternal serum samples were obtained in diagnosis and at 37–37+6 weeks of gestation. Placental tissues were obtained from participants after delivery. ELISA, enzymatic colorimetric and Western blotting were used to evaluate the concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and CRH in maternal serum and expression of CRH in placenta tissues.Results:The UDCA group had greater reduction in maternal serum ALT, AST and TBA levels in ICP patients (all p < 0.01). Maternal serum CRH concentrations in the UDCA group after treatment (122.10 ± 44.20) pg/ml was significantly higher than pretreatment (95.45 ± 26.47) pg/ml (p < 0.01). After treatment, maternal serum CRH concentrations of the UDCA group (122.10 ± 44.20) pg/ml was significantly higher than in the control group (80.71 ± 41.10) pg/ml (p < 0.01). Placental CRH expression in the UDCA group (2.79 ± 1.72) was significantly higher than in the control group (0.69 ± 0.36) (p < 0.01).Conclusions:Maternal serum and placental CRH expression in ICP patients were up-regulated after treatment of UDCA. The up-regulation of CRH expression after UDCA treatment may play an important role in the therapeutic mechanism of ICP. All patients recruited in this study had severe cholestasis (TBA ≥ 40 µmol/L). Further studies are warranted in different gestational weeks and TBA levels to provide more evidence for the correlation between UDCA treatment and CRH expression in ICP patients.

Modulation of Free Corticotrophin-Releasing Hormone, Adrenal and Placental Steroid Hormone Levels Induced by Mifepristone during Pregnancy

Mifepristone is a progesterone receptor antagonist widely used in obstetrics. The aim of the study was to focus on free corticotrophin-releasing hormone (CRH) and also describe modulation of adrenal and placental steroid hormone concentrations induced by mifepristone. Methods: Twenty-six women were enrolled in the study. They received mifepristone for termination of pregnancy. Maternal blood samples were retrieved before administration of mifepristone (600 mg) and 48 h after, just before induction of labor. Bound and free CRH levels were determined in maternal blood concomitantly with cortisol, estriol, progesterone and SDHEA levels. Also paired fetal cord blood samples were collected. Results: Maternal plasmatic CRH level did not change after mifepristone absorption but free CRH increased significantly (0.500 ± 0.326 vs. 0.388 ± 0.303 ng/ml, p = 0.040). A significant decrease of progesterone was observed (83.6 ± 49.3 vs. 95.6 ± 54.9 ng/ml, p = 0.001) with a lower progesterone/estriol ratio (26.9 ± 15.7 vs. 40.7 ± 31.1, p = 0.004). There was a strong association between maternal and fetal free CRH (r² = 0.675, p = 0.001), cortisol (r² = 0.570, p = 0.019), and positive but modest correlation for progesterone (r² = 0.341, p = 0.046) and estriol (r² = 0.379, p = 0.025) levels. Conclusion: Mifepristone has an effect on free CRH level and changes the estriol-progesterone balance.

Non-stress-related factors associated with maternal corticotrophin-releasing hormone (CRH) concentration

During pregnancy, most maternal corticotrophin-releasing hormone (CRH) is secreted by the placenta, not the hypothalamus. Second trimester maternal CRH concentration is robustly associated with the subsequent risk of preterm birth, and it is often assumed that physiological and/or psychological stress stimulates placental CRH release. Evidence supporting the latter assumption is weak, however, and other factors affecting maternal CRH have received little attention from investigators. We carried out a case-control study nested within a large, multicentre prospective cohort of pregnant women to examine potential 'upstream' factors associated with maternal CRH concentration measured at 24-26 weeks of gestation. The predictors studied included maternal age, parity, birthplace (as a proxy for ethnic origin), pre-pregnancy body mass index, height, smoking, bacterial vaginosis and vaginal fetal fibronectin (FFN) concentration. Women with high (above the median) plasma CRH concentration were significantly less likely to have been born in Sub-Saharan Africa or the Caribbean, less likely to be overweight or obese, and more likely to be smokers. Associations with maternal birthplace and BMI persisted in logistic regression analyses controlling for potential confounding variables and when restricted to term controls. A strong (but imprecise and statistically non-significant) association was also observed with high vaginal FFN concentration. Further studies are indicated both in animal models and human populations to better understand the biochemical and physiological pathways to CRH secretion and their aetiological role, if any, in preterm birth.

Levels of maternal serum corticotropin-releasing hormone (CRH) at midpregnancy in relation to maternal characteristics

Corticotropin-releasing hormone (CRH) in maternal blood originates primarily from gestational tissues and elevated levels in midpregnancy have been linked to adverse pregnancy outcomes. Investigators have hypothesized that high levels of maternal stress might lead to elevated CRH levels in pregnancy. Yet a few studies have measured maternal CRH levels among subgroups of women who experience disproportionate socioeconomic disadvantage, such as African-American and Hispanic women, and found that these groups have lower CRH levels in pregnancy. Our goal was to identify maternal characteristics related to CRH levels in midpregnancy and examine which if any of these factors help to explain race differences in CRH levels. The Pregnancy Outcomes and Community Health (POUCH) Study prospectively enrolled women at 15-27 weeks' gestation from 52 clinics in five Michigan communities (1998-2004). Data from the POUCH Study were used to examine maternal demographics, anthropometrics, health behaviors, and psychosocial factors (independent variables) in relation to midpregnancy blood CRH levels modeled as logCRHpg/ml (dependent variable). Analyses were conducted within a sub-cohort from the POUCH Study (671 non-Hispanic Whites, 545 African-Americans) and repeated in the sub-cohort subset with uncomplicated pregnancies (n=746). Blood levels of CRH and independent variables were ascertained at the time of enrollment. All regression models included week of enrollment as a covariate. In addition, final multivariate regression models alternately incorporated different psychosocial measures along with maternal demographics and weight. Psychosocial variables included measures of current depressive symptoms, perceived stress, coping style, hostility, mastery, anomie, and a chronic stressor (history of abuse as a child and adult). In sub-cohort models, the adjusted mean log CRH level was significantly lower in African-Americans vs. non-Hispanic Whites; the difference was -0.48pg/ml (P<0.01). This difference was reduced by 21% (-0.38pg/ml, P<0.01) after inclusion of other relevant covariates. Adjusted mean log CRH levels were also lower among women with <12 years vs. >or=12 years of education (minimal difference=-0.19pg/ml, P<0.05), and among women with high levels of depressive symptoms who did not use antidepressants vs. women with lower levels of depressive symptoms and no antidepressant use (minimal difference=-0.13pg/ml, P<0.01). Log CRH levels were inversely associated with maternal weight (-0.03pg/ml per 10 pound increase, P<.05) but unrelated to smoking and all other psychosocial measures. Results were similar in the subset of women with uncomplicated pregnancies, except that lower CRH levels were also linked to higher perceived stress. African-American women have lower blood CRH levels at midpregnancy and the race difference in CRH levels is reduced modestly after adjustment for other maternal characteristics. CRH levels were not elevated among women with high levels of perceived stress or more chronic stressors. The inverse association between CRH levels and maternal weight is likely due to a hemodilution effect. Relations among maternal CRH levels and maternal race, educational level, and depressive symptoms are difficult to explain and invite further investigation. Our results highlight a group of covariates that merit consideration in studies that address CRH in the context of pregnancy and/or post-partum complications.

Abnormal Progesterone and Corticotropin Releasing Hormone Levels are Associated with Preterm Labour

This study examined whether maternal plasma progesterone and corticotropin releasing hormone (CRH) concentrations can predict the likelihood of preterm labour. Maternal plasma progesterone and CRH concentrations were examined in a total of 51 women. The subject cohort included 20 women who were followed from the beginning of the third trimester (28 to 34 weeks gestation), half of whom delivered early preterm and half of whom were not in labour and subsequently delivered at full term (n = 10 per group). In a follow-up experiment, 31 women who were admitted during labour for delivery were examined, 15 of whom delivered preterm and 16 of whom delivered at full term. Comparisons between women who delivered preterm and those who delivered at full term were made by t-tests. Mean progesterone concentration was approximately 30% lower at 28 to 34 weeks gestation in women who delivered prematurely than in women who delivered at term (P < 0.001). Meanwhile, mean CRH concentration was 6-fold higher at 28 to 34 weeks gestation in women who experienced spontaneous preterm labour than in those who went into labour at term (P < 0.001). Preterm mothers had lower progesterone (P < 0.05) and CRH (P < 0.01) levels during active labour than full-term mothers. Progesterone levels normalised within 24 hours of delivery in preterm mothers, while CRH levels remained slightly elevated (P < 0.01). Maternal progesterone and CRH measurements taken early in the third trimester may be of use as biochemical markers of pregnancies at high risk of premature labour.

Bioassay Research Methodology: Measuring CRH in Pregnancy

There are documented associations between elevated maternal corticotropin-releasing hormone (CRH) levels and adverse pregnancy outcomes. However, reports of these findings often lack sufficient detail and rationale regarding the bioassay methodology. This shortcoming can be problematic for researchers who do not possess in-depth laboratory sciences knowledge but who want to include bioassays in their investigations or to evaluate published reports. The quality and reliability of CRH measurement results can be significantly affected by variables encountered during sample collection, processing, storage, and bioassay. Thus, it is important to establish research laboratory protocols that are based on well-informed rationales and to carefully consider and control for relevant variables. A synthesis of laboratory sciences literature regarding variables affecting CRH measurement in pregnancy is presented. Additionally, consultation with experienced researchers provided an in-depth understanding of CRH measurement. From these sources, a laboratory protocol for clinical research was developed. Multiple variables that are specific to the reliability of CRH measurement in pregnancy have been identified. These include sample collection methods, sample processing, sample integrity, sample storage, and the actual assay selected. The reliability of CRH measurements can be significantly improved by identifying and controlling for variables encountered during sample collection, processing, storage, and bioassay. Adequate methodological details are difficult to glean solely from the published literature, thus consultation with well-informed researchers is necessary. A protocol for CRH bioassay in clinical research is proposed.

Schizophrenia Risk May Rise After Certain Pregnancy Stressor

Schizophrenia Risk May Rise After Certain Pregnancy Stressor

Fetal sex differences in maternal corticotrophin releasing hormone levels during pregnancy for term and preterm deliveries

Fetal sex differences in maternal corticotrophin releasing hormone levels during pregnancy for term and preterm deliveries

Maternal corticotropin-releasing hormone levels during pregnancy and offspring adiposity.

Animal models suggest that fetal exposure to glucocorticoids can program adiposity, especially central adiposity, later in life. We examined associations of maternal corticotropin-releasing hormone (CRH) levels in the late 2nd trimester of pregnancy, a marker of fetal glucocorticoid exposure, with child adiposity at age 3 years. We analyzed data from 199 participants in Project Viva, a prospective cohort study of pregnant women and their children, At age 3 years, the main outcomes were age-sex-specific BMI z score and the sum of subscapular (SS) and triceps (TR) skinfold thicknesses to represent overall adiposity, and ratio of SS to TR (SS:TR) to represent central adiposity. Mean (standard deviation) maternal 2nd trimester log CRH was 4.94 (0.56) pg/mL. At age 3, mean (standard deviation) for BMI z score was 0.52 (1.02); for SS + TR, 16.51 (3.94) mm; and for SS:TR, 0.67 (0.17). Log CRH was mildly inversely correlated with birth weight (r = -0.08), chiefly because of its association with length of gestation (r = -0.21) rather than fetal growth (r = -0.004). After adjustment for sociodemographic factors, maternal smoking, BMI, and gestational weight gain, fetal growth, length of gestation, breastfeeding duration, and (for SS:TR only) child's 3-year BMI, each increment of 1 unit of log CRH was associated with a reduction in BMI z score [-0.43; 95% confidence interval (CI), -0.73, -0.14; p = 0.004] and possible reduction in SS + TR (-1.10; 95% CI, -2.33, 0.14; p = 0.08). In contrast, log CRH was associated with higher SS:TR (0.07; 95% CI, 0.02, 0.13; p = 0.007). Fetal exposure to glucocorticoids, although associated with an overall decrease in body size, may cause an increase in central adiposity.

Corticotropin-Releasing Hormone Stimulates Estrogen Biosynthesis in Cultured Human Placental Trophoblasts1

Estrogens and corticotrophin-releasing hormone (CRH) produced by the placenta play pivotal roles in the control of parturition in human and other primates. There is a strong correlation between maternal CRH and estrogen concentrations throughout gestation. To investigate whether CRH produced locally in the placenta could modulate estrogen production, we obtained human placental trophoblasts from uncomplicated term pregnancies and cultured them for 72 h. Cells were then treated with CRH and with a CRH receptor antagonist, alpha-helical CRH9-41. The results showed that CRH stimulated, but alpha-helical CRH9-41 inhibited, the production of estradiol in a time- and dose-dependent manner. Consistent with this thesis, CRH increased whereas alpha-helical CRH decreased the mRNA levels of STS, CYP19A1, and HSD17B1, the key enzymes for estrogen synthesis. These results suggest that, in the placenta, endogenously produced CRH exhibits a tonic stimulatory effect on estrogen production.

Pattern of maternal serum corticotropin‐releasing hormone concentration during pregnancy in the common marmoset (Callithrix jacchus)

Corticotropin-releasing hormone (CRH), a potent neuropeptide, is produced by the placenta of anthropoid primates. No other mammals, including prosimian primates, are known to produce placental CRH. In humans, placental CRH appears to play an important role in the progression of pregnancy to parturition. Maternal circulating CRH begins to rise early in pregnancy and increases until parturition. Gorillas and chimpanzees share this pattern of increasing maternal CRH during pregnancy with humans. In humans, chimpanzees, and gorillas, maternal CRH and estradiol concentrations are correlated, consistent with the hypothesis that CRH is involved in the biosynthetic pathway for placental estrogen production. In contrast, in baboons, maternal circulating CRH rises precipitously early in pregnancy and then declines, though CRH is detectable until birth. This research was designed to investigate the pattern of maternal circulating CRH in the common marmoset during pregnancy. Blood samples were taken across gestation from nine subjects over 11 pregnancies, and the plasma was assayed for CRH. The pattern of maternal circulating CRH in the common marmoset was similar to that of the baboon, with a rapid rise starting at about 50 days postconception and a peak at approximately 70 days postconception. By 110 days postconception, CRH concentration had plateaued at a significantly lower value. The peak and mean values for CRH were associated with fetal number (e.g., females gestating triplets had higher values than females gestating twins). Urinary estradiol showed no association with plasma CRH concentration. Marmosets appear to differ from the great apes in this regard, and to share a pattern of maternal CRH during pregnancy with the baboon, indicating that the baboon and marmoset pattern may be ancestral. The function of the early rapid rise of CRH in baboons and marmosets, and the significance of this difference between monkeys and apes, are not known.

Maternal prenatal anxiety and corticotropin-releasing hormone associated with timing of delivery.

The high rate of preterm births is an imposing public health issue in the United States. Past research has suggested that prenatal stress, anxiety, and elevated levels of maternal plasma corticotropin-releasing hormone (CRH) are associated with preterm delivery in humans and animals. Studies to date have not examined all three variables together; that is the objective of this paper. Data from 282 pregnant women were analyzed to investigate the effect of maternal prenatal anxiety and CRH on the length of gestation. It was hypothesized that at both 18 to 20 weeks (Time 1) and 28 to 30 weeks gestation (Time 2), CRH and maternal prenatal anxiety would be negatively associated with gestational age at delivery. CRH was also expected to mediate the relationship between maternal prenatal anxiety and gestational age at delivery. Findings supported the mediation hypothesis at Time 2, indicating that women with high CRH levels and high maternal prenatal anxiety at 28 to 30 weeks gestation delivered earlier than women with lower CRH levels and maternal prenatal anxiety. Women who delivered preterm had significantly higher rates of CRH at both 18 to 20 weeks gestation and 28 to 30 weeks gestation (p <.001) compared with women who delivered term. These findings are the first to link both psychosocial and neuroendocrine factors to birth outcomes in a prospective design.