Echocardiographic findings of congenital cardiopathies among fetuses of diabetic pregnant women and their relationship with plasma fructosamine levels

Objective.?To study the occurrence of congenital cardiopathies at echocardiography (CCE) in fetuses whose mothers had preexisting diabetes mellitus (PGDM) and to study the potential of using fructosamine level as a late marker (beyond the first trimester) for CCE.

Methods.?A register study covering 91 pregnant women that underwent routine fetal echocardiography ordered due to PGDM. The first dosage of plasma fructosamine found in 65 medical records was analyzed during prenatal care (20.4?±?8.0 weeks of gestation). The presence or absence of structural or functional CCE was associated with fructosamine levels by logistic regression. We assessed the effect modification odds ratio by maternal age and insulin usage.

Results.?Thirty-four fetuses (52.3% of 65 fetuses) presented CCE. Twenty of them had functional CCE and 14 presented structural CCE. The mean maternal plasma fructosamine level was higher among pregnant women whose fetuses presented CCE than in those whose fetuses did not (2.86?±?0.73?mmol/l, 2.22?±?0.54?mmol/l, respectively, p?<?0.0001). Crude OR for CCE and abnormal plasma fructosamine (>2.68?mmol/l) was 9.6 (2.8–33.7, 95% CI, p?<?0.0001). Adjusted OR by maternal age and insulin usage was 10.9 (2.7–45.2, 95% CI p?<?0.0001).

Conclusions.?An abnormal plasma fructosamine level increases the chances of CCE occurring among referral pregnant women with PGDM.     

The effect of a single course of antenatal corticosteroids on maternal adrenal function at term

Objective: To determine if one course of antenatal corticosteroids at 32 weeks produces maternal adrenal suppression at term.

Methods: The adrenocorticotropic hormone (ACTH) stimulation test was administered at 38 weeks to 11 pregnant women who had received a single course of antenatal betamethasone prior to 33 weeks and to six control subjects.

Results: There was no difference in basal cortisol levels (mean?±?standard deviation) between the two groups: 41.6?±?6.9?μg/dl for controls versus 36.0?±?7.8?μg/dl for the steroid group, p?=?0.16. Peak cortisol levels at 45?min following ACTH stimulation were not different: 61.6?±?3.5?μg/dl for controls versus 55.0?±?2.6?μg/dl for the steroid group, p?=?0.16. The power of the study to detect a statistical difference in the observed peak cortisol levels was greater than 95%. None of the study subjects had laboratory criteria or clinical signs of adrenal suppression.

Conclusions: A single course of betamethasone for women at risk for preterm delivery does not produce adrenal insufficiency at term and stress dose steroids are not recommended.     

Anti-Müllerian hormone as a possible predictor of fecundability in subfertile women over 38 years: a retrospective cohort study

Constitutional delay of puberty (CDP) in otherwise healthy girls is defined as failure to develop secondary sexual features past the age of 13 years (two standard deviations above the mean age at which secondary sexual features appear in the population of girls). The inhibitory action of neuropeptide Y (NPY) on the gonadotropic and somatotropic systems in experimental animals and stimulation by NPY of the hypothalamic–pituitary–adrenal axis have been reported, prompting us to study the levels of NPY, insulin-like growth factor-I (IGF-I) and cortisol in eight girls with CDP and normal weight (body mass index (BMI) 21.7?±?4.5?kg/m²). The results were compared with those from a group of 40 girls (BMI?=?20.0?±?3.1?kg/m²) who demonstrated a normal course of puberty (NP). All girls were studied at menarche (mean age at menarche, study vs. control: 16.4?±?0.7 vs. 12.6?±?0.9 years). To measure NPY and IGF-1 we used a radioimmunoassay method, whereas cortisol was measured with an enzyme immunoassay. Blood was collected between 08.00 and 09.00 following an overnight fast. NPY was higher in girls with CDP (181.6?±106.4?pg/ml) than in girls with NP (55.5?±?26.3?pg/ml; p?<?0.001). In the former group, cortisol was higher (397.3?±?241.6?nmol/l) than in NP girls (142.7?±98.0?nmol/l; p?<?0.01). Levels of IGF-I in CDP girls were lower than in NP girls (558.0?±?122.6 vs. 756.5?±?226.8?ng/ml; p?<?0.01). The results corroborate the involvement of NPY in sexual maturation and its role in delayed puberty.     

Assessment of nitrite oxide and maternal–fetal Doppler parameters during pregnancy

Objective: The objective was to evaluate and compare the whole blood nitrite concentration in the three trimesters of pregnancy. Additionally, we investigate whether there is any relation between nitrite concentrations and Doppler ultrasound analysis of some maternal and fetal vessels.

Methods: Thirty-three healthy pregnant women were examined at the first (11–14 weeks), second (20–24 weeks) and third trimester (34–36 weeks) of pregnancy. In the three exams, we determined the maternal whole blood nitrite concentration and uterine arteries Doppler analysis to determine pulsatility index (PI), and resistance index (RI). In the second and third trimester we also performed fetal umbilical and middle cerebral arteries PI and RI. We compared the concentrations of nitrite in three trimesters and correlated with Doppler parameters.

Results: No difference was observed in the whole blood nitrite concentrations across trimesters: 151.70?±?77.90?nmol/ml, 142.10?±?73.50?nmol/ml and 147.10?±?87.30?nmol/ml; first, second and third trimesters, respectively. We found no difference in correlation between whole blood nitrite concentration and Doppler parameters from the evaluated vessels.

Conclusions: In healthy pregnant women, the nitrite concentrations did not change across gestational trimesters and there was also no strong correlation with Doppler impedance indices from maternal uterine arteries and fetal umbilical and middle cerebral arteries.     

Maternal cardiovascular profiling in the first trimester of pregnancies complicated with gestation-induced hypertension or fetal growth retardation: a pilot study

Abstract

Objective: In this study, we determine whether maternal cardiovascular (CV) profiling can detect first trimester differences between women with uncomplicated pregnancies (UP) and those who will develop gestational hypertensive disorders (GHD) or normotensive fetal growth retardation (FGR).

Methods: Cardiac, arterial, and venous function were evaluated in 242 pregnant women around 12 weeks of gestation, using impedance cardiography (ICG) and combined electrocardiogram – Doppler ultrasonography. After postnatal determination of gestational outcome, first trimester measurements were compared between groups using Mann–Whitney U test for continuous data or Fisher’s Exact test for categorical variables (SPSS 20.0).

Results: Compared to UP, first trimester aortic flow velocity index [71?±?0.96 versus 61?±?4.91 1/1000/s (p?=?0.016)], acceleration index [133?±?2.25 versus 106?±?11.26 1/100/s² (p?=?0.023)] and Heather index [23.1?±?0.35 versus 19.2?±?1.70?Ω/s² (p?=?0.019)] were lower in GHD pregnancies, and first trimester stroke volume [77?±?1.16 versus 67?±?3.97?ml (p?=?0.033)] and cardiac output [7.3?±?0.10 versus 6.2?±?0.31?l/min (p?=?0.025)] were lower in FGR pregnancies.

Conclusions: Maternal CV function in the first trimester of pregnancy differs between UP and those destined to develop GHD or FGR. This can be assessed with non-invasive maternal CV profiling, opening perspectives for the application of this technique in early gestational screening for GHD and FGR.     

Lower placental growth factor and higher free β-hCG and PAPP-A levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia

Background: An imbalance between anti- and angiogenic factors during early placentation is key for the development of preeclampsia. Nevertheless, the majority of studies addressing this issue relate to maternal blood and not the fetal circulation.

Objective: To measure placental growth factor (PlGF), free beta human chorionic gonadotropin (β-hCG), and pregnancy-associated plasma protein-A (PAPP-A) levels in the fetal circulation of near-term pregnancies complicated with severe preeclampsia (n?=?20), and their controls matched for parity, and maternal and gestational age.

Method: Upon delivery, a blood sample was withdrawn from the umbilical artery and vein of each case and its control in order to measure the proposed analytes using direct fluoroimmunoassay.

Results: Preeclampsia cases showed significantly lower median PlGF levels in fetal circulation as compared to controls (25.2 versus 36.9 and 23.6 versus 33.9?pg/mL, artery and vein, respectively, p?0.05). Contrarily, cases displayed higher concentrations of PAPP-A (1024.0 versus 720.9 [median] and 1027.0?±?298.4 versus 690.3?±?401.9 mIU/L, artery and vein, respectively, p?<?0.05), and free β-hCG (mean: 33.9?±?4.3 versus 17.2?±?4.0 and 30.1?±?5.2 versus 13.7?±?3.3?ng/mL, artery, and vein respectively, p?<?0.05).

Conclusion: Lower PlGF and higher PAPP-A and free β-hCG levels were found in the fetal circulation of near-term severe preeclamptic pregnancies. There is a need for more research in this regard.     

Maternal second trimester blood levels of selected heavy metals in pregnancies complicated with neural tube defects

Purpose: Neural tube defects (NTDs) are the most common malformations of the central nervous system (CNS). There is continuing research for the identification of risk factors and interventions for prevention of NTDs. The aim of this study was to investigate the maternal second trimester blood levels of selected heavy metals namely, arsenic (As), cadmium (Cd), mercury (Hg), manganese (Mn), nickel (Ni), and lead (Pb) and their possible relation with the occurrence of NTDs.

Methods: Twenty-one healthy second trimester pregnant women with fetuses affected with NTD (cases) were matched with 21 healthy pregnant women with unaffected fetuses (controls) with respect to age, body mass index (BMI), and gestational age. Maternal blood levels of heavy metals were measured after an overnight fasting period.

Results: No significant differences were observed in terms of maternal blood levels of As, Cd, Hg, and Ni between NTD-affected and unaffected pregnancies. The blood Pb and Mn levels were found to be higher in pregnant women with a fetus affected with NTD when compared with pregnant women with unaffected fetuses (for Pb, in cases 12.3?±?5.5?µg/L, in controls 7.8?±?2.4?µg/L; for Mn in cases 3.6?±?1.4?µg/L, in controls 2.4?±?1.0?µg/L, p?Conclusions: High maternal second trimester blood levels of Pb and Mn during pregnancy are associated with NTDs in the newborn.     

Fibroblast growth factor 23 and 25(OH)D levels are related to abdominal obesity and cardiovascular risk in patients with polycystic ovarian syndrome

Abstract

Fibroblast growth factor 23 (FGF23) and Klotho are extensively studied in relation to bone metabolism and progression of chronic kidney disease. There is very limited information about their role in polycystic ovarian syndrome (PCOS). The aim of the present study was to investigate some bone markers in women with PCOS in relation to obesity and cardiovascular risk. In the study were included 80 patients, divided into three age-matched groups –Non-obese PCOS (n?=?40); Obese PCOS (n?=?20) and Obese control group (n?=?20). Bone marker levels were measured by an enzyme-linked immunosorbent assay. Obese PCOS patients had higher levels of FGF23 and sRANKL, lower levels of 25(OH)D and higher prevalence of vitamin D deficiency compared to non-obese subjects. Patients with abdominal obesity (waist circumference >80?cm) independently of PCOS status had significantly higher levels of FGF23 (112.5?±?86.5 vs. 73.4?±?37.9?pg/ml; p?=?.023) and lower of 25(OH)D (35.8?±?21.4 vs 47.8?±?26.5?nmol/l; p?=?.034). Patients with PCOS at risk of cardiovascular diseases according to AE-PCOS consensus also had increased levels of FGF23 (111.6?±?84.5 vs. 66.5?±?35.1?pg/ml; p?=?.031) and decreased levels of 25(OH)D (31.9?±?16.8 vs. 47.1 vs 28.4?nmol/l; p?=?.017) compared to those not at risk. There was no correlation between bone markers and blood glucose levels, insulin resistance or hormonal levels.     

Unopposed appetite (orexigenic) mechanisms in the near-term ovine fetus: central leptin does not inhibit sucrose ingestion

Objective: Leptin is produced in adipocytes and is present in the term fetus. In the adult, leptin acts centrally to inhibit neuropeptide Y-induced carbohydrate intake. We sought to examine if central leptin alters fetal ingestion of oral sucrose in the near-term ovine fetus.

Methods: Five pregnant ewes and fetuses were prepared with fetal vascular, sublingual and intracerebroventricular (ICV) catheters and esophageal electromyogram electrodes, and studied at 132?±?1 days' gestation (term 145–150 days). Following a 2-h baseline period, 10% sucrose was infused sublingually (0.25?ml/min) for the duration of the study. At time 4?h, leptin (0.075?mg/kg) was administered ICV and fetal swallowing was monitored for an additional 6?h.

Results: During the basal period, fetal swallowing averaged 0.7?±?0.1 swallows/min. Fetal swallowing increased significantly in response to 10% sucrose (1.2?±?0.1 swallows/min; p?<?0.05). In response to ICV leptin, fetal swallowing remained significantly elevated at 2, 4 and 6?h (1.3?±?0.4, 1.4?±?0.3 and 1.5 ±?0.2 swallows/min, respectively; p?<?0.05 vs. control).

Conclusions: These results indicate that central leptin inhibition of sucrose ingestion is not functional in the near-term fetus. We speculate that a leptin-mediated anorexigenic response is not present at birth, such that unopposed appetite stimulatory mechanisms in the newborn may facilitate rapid newborn weight gain despite high body fat levels.     

Low-dose vaginal misoprostol in the management of intrauterine fetal death

Objectives.?To assess the effectiveness and side effects of vaginal misoprostol (Vagiprost® tablet) termination of second and third trimester pregnancy complicated with intrauterine fetal death (IUFD).

Design.?A prospective observational cohort study.

Setting.?Tanta University Hospital.

Patients.?The study carried out on 324 women with fetal demise in the second and third trimesters, from January 2008 to December 2009.

Intervention.?All patients were subjected to history taking, physical examination, and the Bishop Scoring. Application of 25?μg misoprostol in the posterior fornix of the vagina, this was repeated every 4 h over 24 h. We assessed the adverse effects, progress, and outcomes.

Results.?The success rate was 90% and 45% in women in the third and second trimesters, respectively. The mean induction-termination interval was 8.95?±?2.63 and 15.3?±?5.37 h for women in the third and second trimesters, respectively. The induction termination interval correlated negatively with the duration of gestation. Approximately, 90% of second trimester and 55% of third trimester women required oxytocin augmentation. The mean value of total required dose of misoprostol was 166.3?±?7.5 and 120?±?28.79?μg for women in the second and third trimesters, respectively.

Conclusion.?Vagiprost appears to be a safe, effective, practical, and inexpensive method for termination of third trimester pregnancy complicated with of IUFD.     

Assessment of free fetal DNA concentration in maternal plasma during the first trimester of pregnancy: comparative study between EDTA and PPT tubes – pilot study

Objective: To compare ethylenediamine tetraacetic acid (EDTA) tubes and plasma preparation tubes (PPT) for evaluating maternal plasma during the first trimester of pregnancy.

Methods: A cross-sectional study was conducted on 24 male fetuses in women between 6 and 14 weeks of pregnancy. Blood samples (10?mL) were collected and stored in EDTA and PPT tubes. Subsequently, the samples were centrifuged and sent for free fetal DNA extraction by means of the polymerase chain reaction (PCR) technique. The reactions were performed in a real time PCR machine for detecting the amplification products. The genome region chosen for performing the PCR reactions was a target specific for the Y chromosome, in which the DYS-14 marker was amplified only when the DNA was of male sex. The free fetal DNA concentration was given by the threshold cycle (TC). To compare the tubes, the paired Student t-test was used.

Results: The mean gestational age was 11.08?±?2.30 weeks (range: 6–14). The mean TC for PPT was 30.08?±?1.05 (range: 27.08–32.61) and for EDTA, 30.23?±?0.96 (range: 28.01–32.09), but without statistical significance (p?=?0.357).

Conclusion: We did not observe any statistically significant difference in free fetal DNA concentration between the EDTA and PPT tubes.     

Does preeclampsia have any adverse effect on fetal heart?

Objective: To determine whether preeclampsia causes fetal cardiac cell damage by assessing umbilical artery NT-proBNP, cardiac troponin I and homocysteine.

Methods: A cross-sectional study with 73 fetuses between 26 and 40 weeks of gestation was performed. Thirty-three healthy mothers’ fetuses were control group (Group I). While 12 mildly pre-eclamptic mothers’ fetuses constituted Group II, 28 fetuses of severe pre-eclamptic mothers were Group III.

Results: Umbilical cord mean NT-proBNP levels of Group I, II and III are 520.8?±?404.5 pg/ml; 664.2?±?215.9 pg/ml; and 1932.8?±?2979.5 pg/ml, respectively (p?=?0.0001). The number of neonates with NT-proBNP?>?500 pg/mL that indicates severe cardiac damage is higher in Group III (p?=?0.001). The mean homocysteine levels are also statistically significantly higher in Group III. Cardiac troponin I levels are not different between the groups (p?=?0.46).

Conclusion: Increased NT-proBNP and homocysteine might not only indicate some degree of in-utero cardiac cell damage but also feto–placental endothelial injury in the fetuses of severe pre-eclamptic mothers. Our finding that shows no evidence of correlation between cardiac troponin I levels with cell damage and endothelial injury requires further research.     

Severe pre-eclampsia is associated with abnormal trace elements concentrations in maternal and fetal blood

Objective: The study was aimed to compare trace elements concentrations in women with and without severe pre-eclampsia (PE). Methods: A prospective case-control study was conducted comparing 43 parturients with severe PE (who received magnesium sulfate [MgSO4]) and 80 healthy parturients and their newborns, matched for gestational age and mode of delivery. Inductively coupled plasma mass spectrometry (ICPMS) was used for the determination of zinc (Zn), copper (Cu), selenium (Se) and magnesium (Mg) levels in maternal as well as arterial and venous umbilical cord serum. Results: Zn levels (µg/L) were significantly higher in fetal arterial and venous blood of the PE group (947.3?±?42.5 vs. 543.1?±?226, 911.1?±?220.2 vs. 422.4?±?145, p?<?0.001; respectively). Se levels (µg/L) were significantly lower in maternal and fetal arterial and venous cord blood of the PE group (98.6?±?24.2, 110.7?±?19.4, 82?±?17.8 vs. 111.6?±?17.6, 82.1?±?17.4 vs. 107.1?±?25.7, p?<?0.001; respectively). Cu levels (µg/L) were significantly lower in fetal arterial and venous cord blood (581.6?±?367.4 vs. 949?±?788.8, p?=?0.022, 608.3?±?418.1 vs. 866.9?±?812.6, p?=?0.001 respectively) but higher in maternal blood (2264.6?±?751.7 vs. 1048?±?851.1, p?<?0.001). These differences remained significant while controlling for the mode of delivery. Mg levels were significantly higher in the PE group as compared with the control group. Conclusions: Severe PE is associated with abnormal concentrations of Zn, Cu and Se. Therefore, trace elements may have a crucial role in the pathogenesis of severe PE.     

Association between maternal serum 25-hydroxyvitamin D level and pre-eclampsia

Objectives: The objective of the study was to evaluate the association of maternal plasma levels of 25-hydroxyvitamin D (25(OH)D) at late second and third trimester and the risk of pre-eclampsia.

Methods: In this prospective cohort study, maternal plasma 25(OH)D levels were measured at late second and third trimester in 77 women who later developed pre-eclampsia (31 non-severe and 46 severe cases) and 180 women without pre-eclampsia.

Results: The mean gestational age of the timing of the blood sampling was 31.1?±?4.4 at control group, 32.6?±?5.7 at non-severe pre-eclamptic group and 32.3?±?5.4 at severe pre-eclamptic group. The mean 25(OH)D concentration was significantly low in severe pre-eclampsia group (5.8?±?4.5?ng/ml) than non-severe pre-eclampsia (11.8?±?7.3?ng/ml, p?=?0.039) and control groups (14.9?±?12.0?ng/ml, p?<?0.0001). There was no statistically significant difference in 25(OH)D concentration between non-severe pre-eclamptic and control groups (p?=?0.404). In women with 25(OH)D concentration <20?ng/ml, a 12.45-fold increase in the odds of severe pre-eclampsia were detected.

Conclusion: Women with severe pre-eclampsia had low serum 25(OH)D levels. The correlation between maternal 25(OH)D levels and aspartate aminotransferase, alanine transaminase, serum creatinine levels, platelet count were not determined. 25(OH)D levels may be used as an independent predictive marker of severe pre-eclampsia.     

Levels of antibodies against protein C and protein S in pregnancy and in preeclampsia

Objectives.?The clinical relevance of antibodies anti-protein C and anti-protein S in pregnancy remains controversial. We evaluate whether, in the absence of thrombophilic diseases, maternal plasma levels of antibodies (IgM and IgG) change during pregnancy and in preeclampsia (PE), with and without superimposed fetal growth restriction (FGR).

Methods.?A retrospective cohort of 50 women with PE (n = 30) and PE + FGR (n = 20) and 70 controls [first trimester (n = 20); second trimester (n = 20); third trimester (n = 30)] were enrolled in the study.

Results.?In healthy pregnant women, plasma levels of anti-protein C antibodies decreased from first to third trimester and were below the range of positivity. IgM anti-protein-C and anti-protein-S were significantly higher (P < 0.001) in both PE (23.88 ± 10.65 MoM and 43.90 ± 20.45 MoM, respectively) and PE + FGR group (15.95 ± 12.62 MoM and 36.02 ± 27.43 MoM, respectively) than in control group (2.23 ± 3.23 MoM and 1.68 ± 4.075 MoM, respectively), in the presence of unchanged levels of IgG isotype.

Conclusions.?In this study, we first found that the production of anti-protein C and anti-protein S antibodies decreases throughout healthy pregnancies, while they circulate in high levels in women with PE and PE/FGR.     

Cortisol intermediates and hydrocortisone responsiveness in critical neonatal disease

Objective: Therapy-resistant hypotension complicates diseases in neonates. Our objective was to investigate whether lack of therapeutic response to plasma expanders and inotropes associates with serum levels of cortisol and its precursors.

Methods: We investigated 96 infants with hypotension and critical neonatal disease for cortisol metabolism and are divided into responders and non-responders to plasma expanders and inotropes. Serum concentrations of steroids were analysed soon after the onset of volume expansion and inotrope treatment for shock. The 48 non-responders were treated with intravenous hydrocortisone (HC) and serum cortisol concentrations were monitored a week later.

Results: The mean cortisol concentrations did not differ between the responders and non-responders: 13.6?±?2.5 and 12.5?±?4.5?μg/dL, respectively. Dehydroepiandrosterone (37.3?±?19.5 versus 324.0?±?106.3; p < 0.0001) and 17-hydroxy-pregnenolone concentrations were lower in responders than in non-responders. Dehydroepiandrosterone levels in non-responders were inversely associated with postnatal age (r?=?0.50, p < 0.0001). There were no differences in 17-hydroxy-progesterone, 11-deoxy-cortisol and cortisone between the responders and non-responders. Hydrocortisone administration acutely increased blood pressure. Six non-responders who died despite HC administration had low levels of cortisol. The responders had normal serum cortisol after HC treatment.

Conclusion: Precursors of cortisol, proximal to the 3β-hydroxysteroid dehydrogenase activity, accumulated in neonates with hypotension, responding to HC treatment.     

The effects of probiotic supplementation on biomarkers of inflammation,oxidative stress and pregnancy outcomes in gestational diabetes

Objective: This study was designed to evaluate the effects of probiotic supplementation on biomarkers of inflammation, oxidative stress and pregnancy outcomes among subjects with gestational diabetes (GDM).

Methods: This randomized, double-blind, placebo-controlled clinical trial was done among 60 subjects with GDM who were not on oral hypoglycemic agents. Patients were randomly allocated to intake either probiotic capsule containing Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum (2?×?10⁹ CFU/g each) (n?=?30) or placebo (n?=?30) for six?weeks.

Results: Compared with the placebo, probiotic supplementation resulted in significant decreases in fasting plasma glucose (FPG) (?5.3?±?6.7 vs.?+0.03?±?9.0?mg/dL, p?=?.01), serum high-sensitivity C-reactive protein (hs-CRP) (?2.2?±?2.7 vs.?+0.5?±?2.4?μg/mL, p?p?=?.03) and MDA/TAC ratio (?0.0003?±?0.0008 vs.?+0.0009?±?0.002, p?=?.004), and a significant increase in total antioxidant capacity (TAC) levels (+65.4?±?103.3 vs. ?37.2?±?143.7?mmol/L, p?=?.002). Probiotic supplementation did not affect pregnancy outcomes.

Conclusions: Overall, probiotic supplementation among women with GDM for six?weeks had beneficial effects on FPG, serum hs-CRP, plasma TAC, MDA and oxidative stress index, but did not affect pregnancy outcomes.     

Morning plasma cortisol is low among obese women with polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is the most common cause for androgen excess in women. It is associated with wide variety of metabolic disorders. The present study assessed morning plasma cortisol in women with PCOS. One hundred and ninety seven cases and 55 controls were enrolled for this study. The mean age of patients and controls were 23?±?5.6 years and 25?±?4.3 years. One hundred twelve (56%) women with PCOS had BMI >25. Serum cortisol levels were significantly higher in lean PCOS women compared to controls (13.4?±?5.1 versus 11.3?±?4.5, p?<?0.01) and over-weight PCOS women group (13.4?±?5.1 versus 9.3?±?3.2, p?<?0.01). There was a trend for less acne and hirsutism with increase in BMI. Morning plasma cortisol was lower among obese women with PCOS. Morning plasma cortisol correlated negatively with BMI in PCOS women with normal glucose tolerance.     

Leptin Alters Adrenal Responsiveness by Decreasing Expression of ACTH-R, StAR, and P450c21 in Hypoxemic Fetal Sheep

The late gestation increase in adrenal responsiveness to adrenocorticotropin (ACTH) is dependent upon the upregulation of the ACTH receptor (ACTH-R), steroidogenic acute regulatory protein (StAR), and steroidogenic enzymes in the fetal adrenal. Long-term hypoxia decreases the expression of these and adrenal responsiveness to ACTH in vivo. Leptin, an adipocyte-derived hormone which attenuates the peripartum increase in fetal plasma cortisol is elevated in hypoxic fetuses. Therefore, we hypothesized that increases in plasma leptin will inhibit the expression of the ACTH-R, StAR, and steroidogenic enzymes and attenuate adrenal responsiveness in hypoxic fetuses. Spontaneously hypoxemic fetal sheep (132 days of gestation, PO(2) ～15?mm Hg) were infused with recombinant human leptin (n = 8) or saline (n = 7) for 96?hours. An ACTH challenge was performed at 72?hours of infusion to assess adrenal responsiveness. Plasma cortisol and ACTH were measured daily and adrenals were collected after 96?hours infusion for messenger RNA (mRNA) and protein expression measurement. Plasma cortisol concentrations were lower in leptin- compared with saline-infused fetuses (14.8 ± 3.2 vs 42.3 ± 9.6 ng/mL, P < .05), as was the cortisol:ACTH ratio (0.9 ± 0.074 vs 46 ± 1.49, P < .05). Increases in cortisol concentrations were blunted in the leptin-treated group after ACTH(1-24) challenge (F = 12.2, P < .0001). Adrenal ACTH-R, StAR, and P450c21 expression levels were reduced in leptin-treated fetuses (P < .05), whereas the expression of Ob-Ra and Ob-Rb leptin receptor isoforms remained unchanged. Our results indicate that leptin blunts adrenal responsiveness in the late gestation hypoxemic fetus, and this effect appears mediated by decreased adrenal ACTH-R, StAR, and P450c21 expression.