Reduced 11beta-hydroxysteroid dehydrogenase type 2 activity is associated with decreased birth weight centile in pregnancies complicated by asthma

Pregnancies complicated by asthma are associated with an increased risk of low birth weight. Currently, the mechanisms causing this outcome are unknown. To investigate whether impaired placental function may be a determinant, we measured placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity, protein and mRNA, placental CRH mRNA, fetal cortisol, and fetal estriol concentrations at delivery. Asthmatic subjects were classified according to inhaled glucocorticoid intake during pregnancy and compared with a control nonasthmatic group. There was a 25% reduction in neonatal birth weight centile in asthmatic women who did not use inhaled glucocorticoid treatment. This was accompanied by significantly reduced placental 11beta-HSD2 activity, significantly increased fetal cortisol, and a trend toward increased placental CRH mRNA and reduced fetal estriol concentrations. The use of inhaled glucocorticoids for treatment was associated with birth weight centile, 11beta-HSD2 activity, CRH mRNA, fetal cortisol, and estriol concentrations similar to control levels. There was a significant inverse correlation between fetal cortisol and fetal estriol concentrations across all groups. These studies demonstrate that inhaled glucocorticoid intake for the treatment of asthma is associated with improved placental function and fetal outcome, suggesting that inflammatory factors associated with asthma may be detrimental to fetal growth and development in these pregnancies.     

Course of placental 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase mRNA expression during human gestation.

BACKGROUND: During human pregnancy, 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays an important role in protecting the fetus from high maternal glucocorticoid concentrations by converting cortisol to inactive cortisone. Furthermore, 11beta-HSD2 is indirectly involved in the regulation of the prostaglandin inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH), because cortisol reduces the gene expression and enzyme activity of PGDH in human placental cells. OBJECTIVE: To examine developmental changes in placental 11beta-HSD2 and PGDH gene expression during the 2nd and 3rd trimesters of human pregnancies. METHODS: In placental tissue taken from 20 healthy women with normal pregnancy and 20 placentas of 17 mothers giving birth to premature babies, 11beta-HSD2 and PGDH mRNA expression was determined using quantitative real-time PCR. RESULTS: Placental mRNA expression of 11beta-HSD2 and PGDH increased significantly with gestational age (r=0.55, P=0.0002 and r=0.42, P=0.007). In addition, there was a significant correlation between the two enzymes (r=0.58, P<0.0001). CONCLUSIONS: In the course of pregnancy there is an increase in 11beta-HSD2 and PGDH mRNA expression in human placental tissue. This adaptation of 11beta-HSD2 prevents increasing maternal cortisol concentrations from transplacental passage and is exerted at the gene level. 11beta-HSD2 up-regulation may also lead to an increase in PGDH mRNA concentrations that, until term, possibly delays myometrial contractions induced by prostaglandins.     

Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity in ovine placenta by fetal cortisol

The effect of fetal cortisol on the activity of the type 2 isoform of the enzyme, 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD2), was examined in ovine placenta and fetal kidney by measuring tissue 11 beta-HSD2 activity during late gestation when endogenous fetal cortisol levels rise and after exogenous cortisol administration to immature fetuses before the prepartum cortisol surge. Placental 11 beta-HSD2 activity decreased between 128-132 days and term (approximately 145 days of gestation) in association with the normal prepartum increase in fetal plasma cortisol. Raising fetal cortisol levels to prepartum values in the immature fetus at 128--132 days of gestation reduced placental 11 beta-HSD2 activity to term values. In contrast, 11 beta-HSD2 activity in the fetal renal cortex was unaffected by gestational age or cortisol infusion. When all the data were combined, there was an inverse correlation between the log fetal plasma cortisol level at delivery and placental 11 beta-HSD2 activity, expressed both on a weight-specific basis and per mg placental protein. Fetal cortisol therefore appears to be a physiological regulator of placental, but not renal, 11 beta-HSD2 activity in fetal sheep during late gestation. These findings have important implications, not only for glucocorticoid exposure in utero, but also for the local actions of cortisol within the placental tissues that are involved in initiating parturition in the sheep.     

Longitudinal study of serum placental GH in 455 normal pregnancies: correlation to gestational age,fetal gender,and weight

Placental GH is thought to be responsible for the rise in maternal IGF-I during pregnancy and is considered to be important for fetal growth. In this prospective longitudinal study of healthy pregnant women, we investigated determinants of placental GH in maternal serum. Serum was obtained from 455 women with normal singleton pregnancies at approximately 19 and 28 wk gestation. Serum placental GH concentrations were measured by a highly specific immunoradiometric assay, and fetal size was measured by ultrasound. Data on birth weight, gender, prepregnancy body mass index (BMI), parity, and smoking habits were obtained from medical records. Serum placental GH concentrations were detectable in serum from all women as early as 14 wk gestation and increased during pregnancy in all individuals (P < 0.001). Placental GH levels at second examination were found to be higher in women carrying female fetuses [median, 9.0 ng/ml; 95% confidence interval (CI), 4.7-23.0] compared with women carrying male fetuses (median, 8.2 ng/ml; 95% CI, 3.96-19.4; P = 0.004). Similarly, the increase in placental GH between 19 and 28 wk gestation was significantly larger in female fetus bearers than in male fetus bearers (P = 0.002). Placental GH at second examination was positively correlated with gestational age (P = 0.002) and negatively correlated with prepregnancy BMI (P = 0.039). Placental GH correlated with fetal weight at approximately 28 wk gestation (P = 0.002) but did not predict birth weight at term. Our study supports the role of maternal placental GH in the regulation of fetal growth. In conclusion, we found that 1) placental GH levels correlated significantly with fetal size at 28 wk gestation; 2) GH levels were measurable in serum from all women as early as 14 wk gestation; 3) maternal prepregnancy BMI and smoking were determinants of placental GH levels, although their specific effects on the serum maternal levels of placental GH remain to be seen; and 4) women carrying female fetuses have significantly higher placental GH levels compared with women carrying male fetuses at 28 wk gestation.     

Reduced placental 11beta-hydroxysteroid dehydrogenase type 2 mRNA levels in human pregnancies complicated by intrauterine growth restriction: an analysis of possible mechanisms

11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) inactivates cortisol to cortisone. In the placenta 11beta-HSD2 activity is thought to protect the fetus from the deleterious effects of maternal glucocorticoids. Patients with apparent mineralocorticoid excess owing to mutations in the 11beta-HSD2 gene invariably have reduced birth weight, and we have recently shown reduced placental 11beta-HSD2 activity in pregnancies complicated by intrauterine growth restriction. This is reflected in the literature by evidence of hypercortisolemia in the fetal circulation of small babies. In this study we have determined the levels of placental 11beta-HSD2 mRNA expression across normal gestation (n = 86 placentae) and in pregnancies complicated by intrauterine growth restriction (n = 19) and evaluated the underlying mechanism for any aberrant 11beta-HSD2 mRNA expression in intrauterine growth restriction. 11beta-HSD2 mRNA expression increased more than 50-fold across gestation, peaking at term. Placental 11beta-HSD2 mRNA levels were significantly decreased in intrauterine growth restriction pregnancies when compared with gestationally matched, appropriately grown placentae [e.g. at term DeltaCt (11beta-hydroxysteroid dehydrogenase type 2/18S) 12.8 +/- 0.8 (mean +/- SE) vs. 10.2 +/- 0.2, respectively, P < 0.001]. These differences were not attributable to changes in trophoblast mass in intrauterine growth restriction placentae, as assessed by parallel analyses of cytokeratin-8 mRNA expression. No mutations were found in the 11beta-HSD2 gene in the intrauterine growth restriction cohort, and imprinting analysis revealed that the 11beta-HSD2 gene was not imprinted. Although the underlying cause is unknown, 11beta-HSD2 gene expression is reduced in intrauterine growth restriction pregnancies. These data highlight the important role of 11beta-HSD2 in regulating fetal growth, a known factor in determining fetal morbidity but also the subsequent development of cardiovascular disease in adulthood.     

Decreased gene expression of 11beta-hydroxysteroid dehydrogenase type 2 and 15-hydroxyprostaglandin dehydrogenase in human placenta of patients with preeclampsia

Cortisol reduces the activity of the PG-inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) in human placental cells. The objective was to investigate a possible relation between 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), converting cortisol to cortisone, and PGDH gene expression in the placenta of patients with preeclampsia. In placental tissue taken from 20 healthy women with normal pregnancy, 20 premature babies born after labor before term, and 18 neonates after preeclamptic pregnancy, 11beta-HSD2 and PGDH messenger RNA (mRNA) expression was determined using quantitative TaqMan real-time PCR and quantitative competitive PCR. When comparing matched pairs, there were 3-fold lower 11beta-HSD2/glyceraldehyde-3-phosphate dehydrogenase (11beta-HSD2/GAPDH) mRNA levels in placentas of patients with preeclampsia than in controls [0.18 +/- 0.04 relative units (RU) and 0.61 +/- 0.10 RU, P = 0.0003]. We also found a 2-fold reduction in placental PGDH/GAPDH mRNA concentrations (0.28 +/- 0.15 RU and 0.50 +/- 0.18 RU, P = 0.0003). PGDH and 11beta-HSD2 mRNA levels correlated significantly (r = 0.66, P < 0.0001). In term placenta, 11beta-HSD2/GAPDH, but not PGDH, showed a significant correlation to birth weight (r = 0.43, P = 0.01) and to placental weight (r = 0.47, P = 0.01). Results could be confirmed by competitive PCR. We conclude that, in preeclampsia, 11beta-HSD2 mRNA expression is reduced, leading to the known decrease of 11beta-HSD2 activity. By means of an autocrine or paracrine mechanism, the diminished conversion of placental cortisol may lead to reduced PGDH mRNA expression as found in the present study.     

Altered placental function of 11beta-hydroxysteroid dehydrogenase 2 knockout mice

Fetal glucocorticoid exposure is a key mechanism proposed to underlie prenatal "programming" of adult cardiometabolic and neuropsychiatric disorders. Regulation of fetal glucocorticoid exposure is achieved by the placental glucocorticoid "barrier," which involves glucocorticoid inactivation within the labyrinth zone of the murine placenta by 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2). Thus, the absence of placental 11beta-HSD2 may impact on fetal and placental development. The current study investigated transport of amino acids and glucose, key factors required for fetal growth, and vascular development in placentas from 11beta-HSD2(+/+), (+/-), and (-/-) fetuses derived from 11beta-HSD2(+/-) matings. At embryonic d 15 (E15) (term = E19), 11beta-HSD2(-/-) fetal weight was maintained in comparison to 11beta-HSD2(+/+) fetuses. The maintenance of 11beta-HSD2(-/-) fetal weight occurred despite a reduction in placental weight, suggesting that compensatory changes occur in the placenta to maintain function. However, by E18, 11beta-HSD2(-/-) fetal and placental weights were both reduced. Transport studies revealed up-regulation of placental amino acid transport to 11beta-HSD2(-/-) offspring at E15, coinciding with an increase in the expression of the amino acid transporters. Furthermore, at E18, placental glucose transport to 11beta-HSD2(-/-) offspring was markedly reduced, correlating with lower fetal weight and a decrease in glucose transporter 3 expression. Stereological analyses of the labyrinth zone of the placenta revealed that the reduction in placental weight at E18 was associated with restriction of the normal increase in fetal vessel density over the final third of pregnancy. Our data suggest that restriction of fetal growth in 11beta-HSD2(-/-) mice is mediated, at least in part, via altered placental transport of nutrients and reduction in placental vascularization.     

Influence of placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD) inhibition on glucose metabolism and 11beta-HSD regulation in adult offspring of rats

Placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) converts glucocorticoids to 11-keto-products and is believed to play an important role in protecting fetuses from higher maternal glucocorticoid levels. Recent reports have speculated that prenatal glucocorticoid exposure leads to fetal growth retardation and adult offspring hypertension and hyperglycemia. To investigate the effects of placental 11beta-HSD2 inhibition on glucose metabolism and the 11beta-HSD system in adult offspring, pregnant rats were treated with daily injections of carbenoxolone (CBX), an inhibitor of 11beta-HSD. The offspring of the maternal CBX treatment group showed reduced birth weight (treated v control, 5.6 +/- 0.5 v 6.4 +/- 0.4 g, P < .0001). In adult offspring of the maternal CBX treatment group, plasma hemoglobin A1c was significantly increased (7.3% +/- 1.8% v 4.8% +/- 0.3%, P < .01) and glucose intolerance was shown on the oral glucose tolerance test. The gene expression of hepatic 11beta-HSD1 and renal 11beta-HSD2 was decreased 87.6% (P < .05) and 52.3% (P < .01) in adult offspring of the maternal CBX treatment group, whereas renal 11beta-HSD1 was not significantly altered. The change in 11beta-HSD activity corresponded to the change in the gene expression. These results suggest that inhibition of placental 11beta-HSD2 causes growth retardation, glucose intolerance, and partial suppression of the 11beta-HSD system in the offspring.     

Effect of maternal asthma,inhaled glucocorticoids and cigarette use during pregnancy on the newborn insulin-like growth factor axis

BackgroundFetal growth varies in a sex-specific manner in response to maternal asthma during pregnancy, but the mechanisms are unclear.ObjectiveWe examined the influence of maternal asthma severity and associated exposures, inhaled glucocorticoid treatment, maternal cigarette use, and fetal sex on fetal growth and placental function during pregnancy and on the newborn insulin-like growth factor (IGF) axis.Study subjects and designFetal growth was assessed in a prospective cohort of asthmatic and non-asthmatic women (n = 145). At delivery, umbilical vein plasma was collected from male (n = 61, controls n = 16 and asthmatic n = 45) or female (n = 84, controls n = 22 and asthmatic n = 62) fetuses. Cord plasma insulin-like growth factor (IGF) binding protein (BP)-1, IGFBP-3, IGF-1 and IGF-2 were measured by radioimmunoassay and ELISA.ResultsCord plasma IGF-1 was the main component of the neonatal IGF axis altered by asthma and cigarette use. IGF-1 was increased in the presence of mild asthma and a male fetus and decreased in the presence of a female fetus and maternal asthma with cigarette use. IGFBP-3 was also decreased in the female fetuses of pregnancies complicated by asthma and cigarette use. Inhaled glucocorticoid use for the treatment of asthma did not affect the IGF axis. The strongest overall predictor of female birth weight after accounting for asthma severity, inhaled glucocorticoid treatment and cigarette use was IGF-1. For males, the strongest predictor of birth weight was IGFBP-3.ConclusionThe data suggest male and female fetuses institute different strategies in response to adverse pregnancy conditions such as asthma and cigarette use.     

Chronic maternal stress inhibits the capacity to up-regulate placental 11beta-hydroxysteroid dehydrogenase type 2 activity

This study investigated the effects of acute and chronic restraint stress during the third week of pregnancy on placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in rats. Acute exposure to stress on gestational day 20 immediately up-regulated placental 11beta-HSD2 activity by 160%, while chronic stress from day 14 to day 19 of pregnancy did not significantly alter basal 11beta-HSD2 activity. However, the latter reduced the capacity to up-regulate placental 11beta-HSD2 activity in the face of an acute stressor by 90%. Thus, immediate up-regulation of 11beta-HSD2, the feto-placental barrier to maternal corticosteroids, may protect the fetus against stress-induced high levels of maternal corticosteroids, but exposure to chronic stress greatly diminishes this protection.     

Normal female infants born of mothers with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, especially those patients with the salt-losing form, have decreased fertility rates. Pregnancy experience in this population is limited. We report the pregnancy outcomes and serial measurements of maternal serum steroid levels in four women with classic 21-hydroxylase deficiency, three of whom were female pseudohermaphrodites with the salt-losing form. These glucocorticoid-treated women gave birth to four healthy female newborns with normal female external genitalia, none of whom were affected with 21-hydroxylase deficiency. In three women, circulating androgen levels increased during gestation, but remained within the normal range for pregnancy during glucocorticoid therapy. In the fourth patient, androgen levels were strikingly elevated during gestation despite increasing the dose of oral prednisone from 5 to 15 mg/day (two divided doses). Notwithstanding the high maternal serum concentration of androgens, however, placental aromatase activity was sufficient to prevent masculinization of the external genitalia of the female fetus and quite likely the fetal brain, consistent with the idea that placental aromatization of androgens to estrogens is the principal mechanism that protects the female fetus from the masculinizing effects of maternal hyperandrogenism. These four patients highlight key issues in the management of pregnancy in women with 21-hydroxylase deficiency, particularly the use of endocrine monitoring to assess adrenal androgen suppression in the mother, especially when the fetus is female. Recommendations for the management of pregnancy and delivery in these patients are discussed.     

Glucocorticoid-induced apoptosis in human decidua: a novel role for 11beta-hydroxysteroid dehydrogenase in late gestation

Glucocorticoids play a fundamental role in the endocrinology of pregnancy but excess glucocorticoids in utero may lead to abnormalities of fetal growth. Protection against fetal exposure to cortisol is provided by the enzyme 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) located in the human placental trophoblast. By contrast, relatively little is known concerning the function of glucocorticoid-activating 11beta-HSD1, which is strongly expressed within human maternal decidua. To address this we have assessed: i) changes in decidual 11beta-HSD1 expression across gestation and ii) the functional role of glucocorticoids in decidua. Human decidua was collected from women undergoing surgical termination of pregnancy in first (n = 32) and second (n = 10) trimesters, and elective caesarean sections in the third trimester (n = 9). Analysis of mRNA for 11beta-HSD1 by real-time RT-PCR showed increased expression in second (9.3-fold, P < 0.01) and third (210-fold, P < 0.001) trimesters. Studies using primary cultures of decidual cells also revealed higher levels of cortisol generation in the third trimester. Changes in decidual 11beta-HSD1 with gestation were paralleled by increased expression of the apoptosis markers caspase-3 and annexin-V, particularly in cluster designation (CD)10(-VE) non-stromal cells (20-fold in third trimester relative to first trimester). Apoptosis was also readily induced in primary cultures of third trimester decidual cells when treated with cortisol, cortisone, or dexamethasone (all 100 nM for 24 h). The effect of cortisone but not cortisol or dexamethasone was blocked by an 11beta-HSD inhibitor confirming the functional significance of endogenous cortisol generation. These data show that autocrine metabolism of glucocorticoids is an important facet of the feto-placental unit in late gestation and we propose that a possible effect of this is to stimulate programmed cell death in human decidua.     

A longitudinal study of intrauterine growth and the placental growth hormone (GH)-insulin-like growth factor I axis in maternal circulation: association between placental GH and fetal growth

The aim of the study was 1) to evaluate the association of maternal serum levels of placental GH and IGF-I with fetal growth, and 2) to establish reference data for placental GH, IGF-I, and IGF-binding protein-3 (IGFBP-3) in normal pregnancies based on longitudinal measurements. A prospective longitudinal study of 89 normal pregnant women was conducted. The women had, on the average, seven blood samples taken and three ultrasound examinations performed. All had normal umbilical artery pulsatility indexes during pregnancy and gave birth to singletons between 37 and 42 wk gestation with birth weights above -2 SD. Placental GH levels were detectable in all samples from as early as 5 wk gestation and increased significantly throughout pregnancy to approximately 37 wk when peak levels of 22 ng/ml (range, 4.64-69.22 ng/ml) were reached. Subsequently, placental GH levels decreased until birth. The change in placental GH during 24.5-37.5 wk gestation was positively associated with fetal growth rate (P = 0.027) and birth weight (P = 0.027). Gestational age at peak placental GH values (P = 0.007) was associated with pregnancy length. A positive association between the change in placental GH and the change in IGF-I levels throughout gestation was found in a multivariate analysis (r(2) = 0.42; P < 0.001). There was no association between placental GH and IGFBP-3 levels. The change in IGF-I throughout gestation (P = 0.039), but not placental GH, was significantly positively associated with placental weight at birth. We found a significant association between placental GH and fetal growth. In addition, we found a highly significant association between the increase in placental GH and the increase in IGF-I. The gestational age at peak placental GH levels was associated with pregnancy length.     

Effects of cortisol and oestradiol on hepatic 11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor proteins in late-gestation sheep fetus

In the late-gestation sheep, increased fetal plasma cortisol concentration and placental oestradiol (E(2)) output contribute to fetal organ maturation, in addition to the onset of parturition. Both cortisol and E(2) are believed to regulate the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which interconverts bioactive 11-hydroxy glucocorticoids and their inactive 11-keto metabolites. 11beta-HSD1, abundantly expressed in fetal liver, operates primarily as a reductase enzyme to produce bioactive cortisol and thus regulates local hepatic glucocorticoid concentrations. Cortisol acts through the glucocorticoid receptor (GR) present in the liver. In this study, we examined the effects of cortisol and E(2) on hepatic 11beta-HSD1 and GR in the liver of chronically catheterized sheep fetuses treated with saline (n=5), cortisol (1.35 mg/h; n=5), saline+4-hydroxyandrostendione, a P450 aromatase inhibitor (4-OHA; 1.44 mg/h; n=5), or cortisol+4-OHA (n=5). Cortisol infusion resulted in increased plasma concentrations of fetal cortisol and E(2); concurrent administration of 4-OHA attenuated the increase in plasma E(2) concentrations. Using immunohistochemistry, we showed that fetal hepatocytes expressed both 11beta-HSD1 and GR proteins. Cortisol treatment increased GR in both cytosol and nuclei of hepatocytes; concurrent administration of 4-OHA was associated with distinct nuclear GR staining. Western blot revealed that cortisol, in the absence of increased E(2) concentrations, significantly increased concentrations of 11beta-HSD1 (34 kDa) and GR (95 kDa) proteins. 11beta-HSD1 enzyme activity was measured in the liver microsomal fraction in the presence of [(3)H]cortisone (10(-)(6) M) or [(3)H]cortisol (10(-)(6) M) and NADPH (reductase activity) or NADP(+) (dehydrogenase activity) respectively. 11beta-HSD1 reductase activity was significantly greater in the presence of cortisol. In summary, we found that, in sheep during late gestation, cortisol increased both 11beta-HSD1 and GR in the fetal liver, and these effects were accentuated in the absence of increased E(2).     

Prenatal glucocorticoid exposure leads to offspring hyperglycaemia in the rat: studies with the 11 b -hydroxysteroid dehydrogenase inhibitor carbenoxolone

Summary Recent human epidemiological studies have linked low birth weight with a substantially increased risk of non-insulin-dependent diabetes mellitus in later life. These data suggest that the intrauterine environment plays a crucial role in determining later glucose homeostasis, but the mechanism is unknown. We have proposed that exposure of the fetus to excess maternal glucocorticoids may underpin the epidemiological findings. Normally placental 11 β -hydroxysteroid dehydrogenase type 2 (11 β -HSD-2) protects the fetus from the normally higher maternal levels of glucocorticoids by inactivating corticosterone and cortisol to inert 11-keto products. Here we show that administration of carbenoxolone, an inhibitor of placental 11 β -HSD 2, to pregnant rats, leads to a significant reduction in average birth weight (20 % fall). At 6 months of age, the male offspring of carbenoxolone-treated pregnancies had similar weights to controls, but showed significantly higher fasting plasma glucose (6.0 ± 0.3 vs 4.8 ± 0.2 mmol/l; p < 0.01) and exhibited significantly greater plasma glucose (10 % higher) and insulin (38 % higher) responses to an oral glucose load. These effects of carbenoxolone require intact maternal adrenal glands suggesting that inhibition of feto-placental 11 β -HSD 2 is key. These data support the notion that defiency of placental 11 β -HSD, by exposing the fetus to excess maternal glucocorticoids, reduces growth and predisposes to hyperglycaemia in later life. [Diabetologia (1996) 39: 1299–1305] Received: 7 May 1996 and in revised form: 26 July 1996     

CORTISOL BINDING CAPACITY AND OESTROGEN CONCENTRATIONS IN MATERNAL AND CORD PLASMA IN PREGNANCIES WITH NORMAL AND ANENCEPHALIC FETUSES

The cortisol binding capacity of maternal and cord plasma samples obtained at delivery from fifteen women and their normal infants and from seven women and their anencephalic infants was measured at 4°C by a gel filtration technique. The concentration of oestrogen in these samples was measured by radioimmunoassay. There was no significant difference (t test) between the cortisol binding capacity of peripheral plasma from women with normal infants (1.5±0.24 μmol/l, mean ± SD) and from those who delivered anencephalic infants (1.35 ± 0.30μmol/l), nor between the cortisol binding capacity of cord plasma from anencephalic infants (0.47 ± 0.04 μmol/l) and that of normal infants (0.37 ± 0.10 μmol/l). However, mean oestrogen concentrations in maternal and cord plasma from the pregnancies with an anencephalic fetus were significantly lower (P<0.01) than in the corresponding samples from normal pregnancy. It is concluded that oestrogen concentrations in maternal and cord plasma in normal pregnancy at delivery are much greater than those required to account for the increase in plasma cortisol binding capacity. Since plasma cortisol binding capacity in pregnancy with an anencephalic fetus is not diminished, the reduced excretion of corticosteroids relative to normal pregnancy in this condition is unlikely to be due to alterations in cortisol metabolism associated with a lower plasma cortisol binding capacity.