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PubMed1976

Placental function and renal tract studies in pre-eclampsia with proteinuria and long-term maternal consequences.

A total of 99 patients with pre-eclampsia and proteinuria were managed conservatively between 30 and 37 weeks of gestation, based on serial urinary estriol, liquor amnii, and renal function studies. The over-all perinatal wastage was 14 per cent, but was 35 per cent in association with subnormal estriol excretion and oligohydramnios (less than 250 ml.). In severe pre-eclampsia (blood pressure greater than 170/110 mm. Hg with proteinuria greater than 5 Gm. per liter) the incidence of subnormal estriol was 73 per cent and, becuase of this and the associated maternal hazards, conservative treatment had little place. However, in less severe pre-eclampsia with proteinuria early in the third trimester, this prospective study, based on serial placental and renal function tests, showed that frequently the pregnancy could be prolonged and fetal losses due to prematurity avoided. It should be stressed that such conservative treatment should not be continued when there are strong clinical contraindications. Irrespective of the severity of the prior pre-eclampsia, it was unusual for patients to show residual hypertension, proteinuria, or abnormal pyelography at their postnatal examination. Postpartum renal biopsy showed either normal histology or regression of the classical glomerular lesion in 77 per cent of cases.

Amniotic Fluid↗
PubMed1977

Further investigation on the predictive value of human placental lactogen in high-risk pregnancies.

Blood samples were taken from 254 women with pregnancies with various complications and 119 completely normal pregnant women for measurement of serum human placental lactogen (hPL) during the third trimester. The value of this test in the management of these pregnancies was retrospectively evaluated through details of outcome. Serum hPL and urinary estriol were compared as tools for assessment of fetal condition. Serum hPL was found to be very efficient in the prenatal diagnosis of intrauterine growth retardation associated with maternal hypertension. Low hPL levels were recorded in all severely hypertensive patients who were delivered of small-for-dates infants (a 100 per cent prediction rate), while 30 per cent of these patients had normal estriol values. Prediction rate of postmature infants by serum hPL level was 70 per cent as compared to 50 per cent by urinary estriol level. The diagnostic significance of low hPL levels is emphasized, with stress upon its value in early detection of unfavorable intrauterine environment. The importance of preterm deliveries in pregnancies involving intrauterine growth retardation and low hPL levels is discussed and demonstration cases are presented.

Adult↗
PubMed1979

Corticosteroid-binding globulin and estrogens in maternal and cord blood.

Corticosteroid-binding globulin (CBG) is produced by the liver in small concentrations and binds steroids with high affinity. Its concentration in the blood is sensitive to endogenous or exogenous estrogens in a dose-response manner and serves as a biological assay for estrogens. CBG concentrations were measured in sera collected from maternal and umbilical vein blood during labor and delivery and at elective cesarean section and correlated with endogenous estradiol and estriol concentrations. CBG and estradiol concentrations of maternal blood were significantly exceeded those of maternal serum. A highly significant increase in cord blood estriol concentration was found following vaginal delivery compared to elective cesarean section, indicating an increase in adrenal activity due to the stress of labor. CBG levels correlated directly with maternal estradiol but not estriol cencentrations. Cord blood CBG concentration varied little despite a wide range of estrogen concentrations. The physiologic significance of CBG concentrations in maternal and fetal blood is discussed.

Cesarean Section↗
PubMed1986

Fetoplacental steroid metabolism in prolonged pregnancies.

The response to an intravenous load of 50 mg of dehydroepiandrosterone sulfate given to women with a pregnancy prolonged to more than 42 weeks was compared to the response in control pregnant women at 40 weeks. The half-life of dehydroepiandrosterone sulfate was longer in the prolonged pregnancy group than in the control group (mean +/- SEM, 3.64 +/- 0.24 hour versus 2.78 +/- 1.08 hour, p less than 0.05), and the rises of serum free estrone and free estradiol 4 hours after infusion were less in the prolonged pregnancy group than in the control group. Maternal venous and umbilical venous estrone, estradiol, free estriol, and dehydroepiandrosterone sulfate levels were compared in samples from control, postmature, and postterm groups. Umbilical estriol concentrations were significantly less in the postmature group (67.8 +/- 9.5 ng/ml, mean +/- SEM) than in the control group (136 +/- 22.8 ng/ml, mean +/- SEM, p less than 0.01), but there were no significant differences between dehydroepiandrosterone sulfate, estrone, and estradiol levels. Maternal venous estriol levels were lower in the postmature group (13.3 +/- 2.1, p less than 0.05) than in the control group (25.0 +/- 4.9). A reduction in overall placental estrogen production was indicated by the results of the dehydroepiandrosterone sulfate loads in the patients with prolonged pregnancy, yet the normal umbilical venous estrone and estradiol levels do not fit this conclusion. There is no explanation for the discrepancy at this time.

Dehydroepiandrosterone↗
PubMed1988

The effects of syphilis on endocrine function of the fetoplacental unit.

Several pregnancy complications that are thought to cause chronic intrauterine stress have been found to lead to inappropriate fetal development and reductions in estrogen production. In the current study we sought to evaluate the fetoplacental unit in pregnancies complicated by maternal syphilis (n = 37), with and without fetal infection. Maternal 17 beta-estradiol and estriol levels were reduced during the third trimester in women with syphilis when compared with those in women with uncomplicated pregnancies. Serum progesterone levels were within normal limits or else were increased in women with syphilis. When compared with data in age- and weight-matched control infants of women having no pregnancy complications, umbilical cord serum levels of dehydroepiandrosterone sulfate, the major fetal adrenal precursor of placental estrogens, were subnormal (897 +/- 597 ng/ml, mean +/- SD) in 12 newborn infants with congenital syphilis (33.9 +/- 4.2 weeks' gestation, birth weight 2020 +/- 719 gm); such infants also had excessive serum levels of cholesterol (103 +/- 37 mg/dl). Dehydroepiandrosterone sulfate (1883 +/- 907 ng/ml) and cholesterol (58.1 +/- 13.9 mg/dl) levels were within normal limits in 19 uninfected infants of women with syphilis (38.6 +/- 2.4 weeks' gestation, birth weight 2861 +/- 660 gm). Cortisol levels were increased and estriol levels were decreased in both groups of neonates of women with syphilis compared with those in control neonates. These findings are suggestive that estrogen production often is reduced in pregnancies complicated by syphilis; the reduction in estriol appears to be largely due to reduced fetal adrenal dehydroepiandrosterone sulfate production. The reduction in 17 beta-estradiol levels may be due to alterations in maternal precursor synthesis. Although placental progesterone formation appears to be normal in women with syphilis, a deficiency in placental aromatase activity also is possible.

Cholesterol↗
PubMed1985

Cell growth and cell proliferation may be dissociated in the mouse uterine luminal epithelium treated with female sex steroids.

The mouse uterine epithelium under various hormonal regimes is a good system to identify biochemical events associated with cell growth, DNA synthesis and cell division. This is because estradiol-17 beta stimulates the cells to undergo a synchronized wave of DNA synthesis and cell division. Estriol, on the other hand, also stimulates DNA synthesis but because of the rapid loss of this hormone from the tissue some of the cells abort, giving a constant epithelial cell number. Three days of progesterone pretreatment, however, completely suppresses the estradiol-17 beta-induced wave of DNA synthesis and cell proliferation. Using these hormonal treatments we have shown that both estradiol-17 beta and estriol stimulate protein and rRNA synthesis with the concomitant increase of protein and rRNA per mg of DNA. These macromolecules accumulated in direct proportion to the fraction of cell committed to DNA synthesis. Estriol, however, did not sustain the growth responses and at the peak of DNA synthesis both rRNA and protein synthesis had returned to control levels. Progesterone pretreatment, despite inhibiting the proliferative response, failed to inhibit any of the estradiol-17 beta-induced increases in protein and rRNA synthesis. Indeed 12 h after estradiol-17 beta injection the cells had identical protein and rRNA contents, regardless of whether they had been exposed to progesterone or not. The present data therefore suggests that in the uterine epithelium cell growth as defined by protein and rRNA accumulation and DNA synthesis represents two independently regulated pathways.

Animals↗
PubMed1991

Estrogens inhibit copper and cell-mediated modification of low density lipoprotein.

The effects of estrogens on LDL modification by copper ions, U 937 monocyte-like cells or endothelial cells was studied by determination of the lipid peroxidation product content and measurement of the relative electrophoretic mobility. The presence of estradiol, estriol and estrone inhibited LDL oxidation in a dose-dependent manner in the range of concentrations from 5 to 50 microM. In the case of oxidation by Cu2+, the decreasing order of efficiency was: estradiol, estriol, estrone. In monocyte-induced oxidation, the protective effect of estrogens was more marked, and the order of efficiency was the same, except that estrone was as active as estriol. Pretreatment of monocyte cells with estrogens also inhibited the subsequent modification of LDL by these cells, tested in the absence of the hormones. Testosterone had no effect in all the studied systems. Furthermore, the degradation by J774 macrophage like cells of LDL modified either by Cu2+ or monocytes was markedly reduced when modification has been performed in the presence of estrogens. Since oxidative modification of LDL is believed to be involved in the appearance of atherosclerotic plaques, this effect of estrogens might be related to their protective action against atherosclerosis.

Animals↗
PubMed1984

Effect of estrogens on DMBA induced breast tumors.

Evidence is presented for the anti-carcinogenic activity of estriol when this hormone is administered to 50-55 day old SD rats prior to treatment with DMBA. In control and estradiol treated animals, 85-100% of animals developed breast tumors regardless of dose of steroid. Low doses of estriol (1 microgram/day) offered some protection against tumorigenesis but at levels exceeding 10 micrograms/day only 20-35% of animals developed tumors even when observed for 180 days following DMBA ingestion. Furthermore, the mean time for tumor production is greatly increased in the presence of E3. Short term (2 weeks) administration offered no protection against tumor formation, suggesting that the effect of estriol probably relates to the promotion stage of tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Effect of ampicillin or amoxycillin administration on plasma and urinary estrogen levels during normal pregnancy.

Urinary estrogen excretion and plasma levels of conjugated and unconjugated 17 beta-estradiol and estriol were measured in 10 healthy, pregnant women before, during and after a 5-day course of orally administered ampicillin (2 g/day) or the same dose of amoxycillin. On the second and third day of ampicillin treatment the plasma level of conjugated estriol and the urinary estrogen level were lower than pretreatment values, but then returned to basal values despite continuing treatment. Plasma concentrations of conjugated and unconjugated 17 beta-estradiol and of unconjugated estriol did not show any significant change during treatment. Hormone changes in women on amoxycillin were qualitatively similar to but smaller and less consistent than those induced by ampicillin. The results indicate (1) that the use of amoxycillin instead of ampicillin in pregnancies that require estrogen monitoring of feto-placental function, has little clinical advantage, and (2) that the adverse effect of therapeutic doses of ampicillin (and amoxycillin) on estrogen levels during pregnancy may be less important than is commonly assumed.

Amoxicillin↗
PubMed1977

Hormone changes in relation to the time of fetal death after prostaglandin-induced abortion.

The changes in unconjugated estradiol-17beta and estriol, progesterone and chorionic somatomammotropin (HCS) in peripheral plasma have been studied in 18 women at 30-minute intervals following intra-uterine prostaglandin E2 administration for therapeutic termination of second trimester pregnancy. The hormonal changes were related to the time of fetal death detected by the disappearance of fetal heart pulsations. Prostaglandin E2 was given by the intra-amniotic route with urea (5 patients) or with intravenous oxytocin (5 patients), or by the extra-amniotic route with intravenous oxytocin (8 patients). Fetal death occurred rapidly with intra-amniotic PGE2, but usually at a late stage with extra-amniotic PGE2. Three fetuses in the extra-amniotic group died at or just before abortion. A variety of fetal heart changes were noted and the time of fetal death did not appear to influence the time of abortion within each treatment subgroup. Estradiol and estriol showed a sligh but persistent fall over 24 hours prior to induction of abortion. A more rapid fall usually occurred after induction, with a consistent fall around the time of fetal death. Progesterone and HCS usually fell much less before and immediately after fetal death. A marked rise in estradiol sometimes occurred before fetal death, particularly in the intraamniotic PGE2 and urea subgroup. Estriol levels declined more rapidly before than after fetal death, whereas fetal death had less consistent effects on the other hormones. All hormones had usually fallen considerably at the time of abortion, and in some individuals marked fluctuations in hormone levels were seen.

Abortion, Induced↗
PubMed1981

Progesterone as an immunologic blocking factor in human pregnancy serum.

The influence of estriol and progesterone on lymphocyte reactivity was examined by testing the cytotoxic effect on human embryonic fibroblast cells of non-pregnant women's lymphocytes incubated with different concentrations of estriol and progesterone and with complete and progesterone-depleted third trimester pregnancy sera. Progesterone, but not estriol, had a significant inhibitory effect on lymphocyte cytotoxicity at concentrations comparable to those present in pregnancy serum. 95% depletion of progesterone from pregnancy sera caused an 80% loss of inhibitory activity on lymphocyte cytotoxicity. These data suggest that the blood level of progesterone in pregnancy is sufficient to depress lymphocyte reactivity and that progesterone is responsible for the greater part of the serum inhibitory activity in at least the later stages of pregnancy.

Binding, Competitive↗
PubMed2006

Detection of endocrine disrupters: evaluation of a Fish Sexual Development Test (FSDT).

Managed by the Organisation for Economic Co-operation and Development (OECD), a comprehensive work is carried out in numerous laboratories to develop test guidelines for the detection of endocrine disrupting chemicals in humans, and various animal species. Development of tests to detect chemicals with endocrine disrupting properties in fish is a part of that work. A Fish Sexual Development Test (FSDT) (an extension of the existing OECD TG 210, fish early life stage toxicity test), proposed as an international test guideline for the detection of endocrine disrupting chemicals, was evaluated by water exposure of juvenile zebrafish to the three natural estrogens: estrone, 17beta-estradiol, and estriol and the synthetic androgen trenbolone (trenbolone acetate). As endpoints, vitellogenin induction and histological changes including changes in sex ratios were investigated. The sex ratio was significantly altered towards females from 49 ng/l estrone, 54 ng/l 17beta-estradiol and 22 microg/l estriol, respectively. An all male population was observed from exposure to 9.7 ng/l trenbolone and above. Significant vitellogenin induction in whole body homogenate was measured after exposure to 14 ng/l estrone, 54 ng/l 17beta-estradiol and 0.6 mug/l estriol, respectively. Significant vitellogenin reduction was measured after exposure to 193 ng/l trenbolone or higher. The present results provide strong evidence that the FSDT is a sensitive test toward estrogenic and especially androgenic exposure and the validation of the FSDT as an OECD test guideline should continue.

Animals↗
PubMed1992

Multiple-marker screening in pregnancies with hydropic and nonhydropic Turner syndrome.

OBJECTIVE: The combination of maternal serum alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin levels and maternal age has been used to increase the sensitivity of screening for fetal Down syndrome and trisomy 18 in early-second-trimester pregnancies. We hypothesized that a unique pattern of these analytes also may be characteristic of fetal Turner syndrome, with or without hydrops. STUDY DESIGN: We studied preamniocentesis, second-trimester maternal serum specimens from seven hydropic and eight nonhydropic cases of fetal Turner syndrome. Clinical and pathologic records were reviewed. Statistical analysis of the data was performed by the rank sum test. RESULTS: In both hydropic and nonhydropic cases, alpha-fetoprotein levels were slightly reduced, and unconjugated estriol levels were markedly reduced. In hydropic pregnancies human chorionic gonadotropin levels were elevated, and nonhydropic pregnancies had low human chorionic gonadotropin levels (p = 0.001). CONCLUSIONS: The results suggest that the morphologic defect of hydrops, rather than the aneuploidy itself, is responsible for the elevation in human chorionic gonadotropin. In conjunction with the low unconjugated estriol levels, the elevation in human chorionic gonadotropin levels will result in the prenatal identification of hydropic fetal Turner syndrome pregnancies as being at increased risk for fetal Down syndrome.

Biomarkers↗
PubMed1996

Maternal serum analyte levels after first-trimester multifetal pregnancy reduction.

OBJECTIVE: Our purpose was to assess the effect of multifetal pregnancy reduction on maternal serum levels of analytes used for screening low-risk women for fetal chromosome abnormalities and neural tube defects. STUDY DESIGN: Peripheral blood samples were obtained between 15.09 and 20.9 weeks' gestation from 10 consecutive women who had undergone first-trimester multifetal pregnancy reduction. The samples were assayed for levels of alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol. Analyte concentrations were interpreted within our maternal serum screening program. RESULTS: Levels of alpha-fetoprotein were significantly elevated in all samples. In each pregnancy levels of human chorionic gonadotropin and unconjugated estriol were consistent with the number of continuing gestations. CONCLUSIONS: First-trimester multifetal reduction does not alter second-trimester levels of human chorionic gonadotropin and unconjugated estriol. Further study is needed to determine whether these analytes could be used to screen pregnancies for fetal chromosome abnormalities after first-trimester multifetal reduction.

Chorionic Gonadotropin↗
PubMed1996

The effect of ovulation induction on the concentration of maternal serum relaxin in twin pregnancies.

OBJECTIVE: Our purpose was to determine the effects of fetal number, various ovulation induction treatments, and placental hormones on the concentration of maternal serum relaxin. STUDY DESIGN: The concentrations of relaxin, human chorionic gonadotropin, estriol, and alpha-fetoprotein were determined in blood samples drawn at 16 to 18 weeks for prenatal diagnosis in 72 singleton and 115 twin pregnancies and analyzed by one-way analysis of variance, correlation analysis, and stepwise multiple linear regression of the log-transformed data. RESULTS: The maternal serum concentrations of each of the four measured hormones were significantly higher in the twin pregnancies than in the singleton pregnancies: 1.4-fold for relaxin, 1.9-fold for human chorionic gonadotropin, 1.9-fold for estriol, and 2.2-fold for alpha-fetoprotein (all p < 0.01). The concentrations of each of the four hormones were significantly correlated with each of the others and with the number of fetuses (p < 0.01), except that estriol was not significantly correlated with human chorionic gonadotropin. The serum relaxin concentration in twin pregnancies after treatment with follicle-stimulating hormone and luteinizing hormone (menotropins) (n = 10) was 3.3-fold that in twins resulting from spontaneous ovulation (n = 89, p < 0.01). In twins resulting from in vitro fertilization or gamete intrafallopian transfer (n = 9) the serum relaxin concentration was 2.6-fold higher than in twins resulting from spontaneous ovulation (p < 0.01). The effect of clomiphene citrate (1.2-fold, n = 7) failed to reach statistical significance. CONCLUSIONS: The second fetus causes a 1.4-fold increase in the concentration of maternal serum relaxin in twin pregnancies. Induction of ovulation with menotropins causes an additional 3.3-fold increase, whereas in vitro fertilization or gamete intrafallopian transfer treatment causes an additional 2.6-fold increase over that seen in twin pregnancies that followed spontaneous ovulation.

Chorionic Gonadotropin↗
PubMed1999

A high-sensitivity alternative to "routine" genetic amniocentesis: multiple urinary analytes, nuchal thickness, and age.

OBJECTIVE: Our purpose was to evaluate the Down syndrome screening efficiency of a new algorithm consisting of multiple urinary biochemical and ultrasound markers for use in high-risk groups such as women of advanced maternal age. STUDY DESIGN: The urinary beta-core fragment of human chorionic gonadotropin (beta-core fragment) and total urinary estriol, along with fetal nuchal thickness, were measured prospectively in pregnant women who were undergoing genetic amniocentesis at midtrimester (15 to 24 weeks). The most common indication for amniocentesis was advanced maternal age (90.2%). An analyte ratio (beta-core fragment/total estriol ratio) was developed. The values were expressed as multiples of the normal median. An increase in the observed nuchal thickness (delta nuchal thickness) above that expected on the basis of the biparietal diameter was calculated. On the basis of the mean and standard deviations of the urinary analyte ratio in normal fetuses and also Down syndrome, we calculated individual Down syndrome likelihood ratios for each of the two parameters, using gaussian analysis. The product of the likelihood ratios, based on delta nuchal thickness and urinary beta-core fragment-total estriol values times the maternal age-related risk, gave the overall Down syndrome risk. The screening efficiency of our algorithm at various risk thresholds was determined. RESULTS: There were 13 (2.8%) cases of Down syndrome in a total study population of 457. At a risk threshold of >1 in 70, the sensitivity was 92.3% for a false-positive rate of 4.5%. Corresponding values at a risk threshold of >1 in 78 were a sensitivity of 100% with a false-positive rate of 5.2%. CONCLUSION: By combining urinary analyte, nuchal thickness, and maternal age data, we achieved a high Down syndrome detection rate with a low false-positive rate. This algorithm would be attractive as an alternative to "routine" amniocentesis based solely on advanced maternal age. The potential benefits of this protocol could include a significant reduction in the rate of amniocentesis, along with substantial savings in medical expenditures.

Adult↗
PubMed2003

Nausea and vomiting in pregnancy in relation to prolactin, estrogens, and progesterone: a prospective study.

OBJECTIVE: To assess pregnancy hormone levels in relation to nausea with or without vomiting. METHODS: In the context of a prospective cohort study, 262 white pregnant women in Boston were observed through delivery. Maternal blood was collected at 16 and 27 weeks' gestation and serum levels of estradiol, estriol, progesterone, prolactin, and sex hormone-binding globulin were determined. Information on sociodemographic and medical variables was collected through an interviewer-administered questionnaire and review of medical records. At the 27th gestational week, nausea with or without vomiting at any time during the index pregnancy was ascertained. RESULTS: By the 27th gestational week, 209 women (79.8%) had experienced nausea with or without vomiting. There was a substantial and statistically significant (P <.01) inverse association of prolactin with nausea with or without vomiting at both the first and the second samplings, with or without adjustment for the other measured compounds. Estradiol was positively associated with nausea with or without vomiting risk, but the association was evident only after adjustment for the other measured compounds (P values of.06 and.07 at the first and second samplings, respectively). We found no evidence that estriol, progesterone, or sex hormone-binding globulin was related to nausea with or without vomiting at either the 16th or the 27th week of pregnancy. CONCLUSION: Our results point to lower levels of prolactin and, perhaps, higher levels of estradiol as contributing to or correlating with the occurrence of nausea with or without vomiting at any time during the pregnancy until the 27th gestational week. We found no evidence that estriol, progesterone, or sex hormone-binding globulin is associated with this condition.

Adult↗
PubMed2000

Female sex steroids: effects upon microglial cell activation.

Multiple sclerosis occurs more commonly in females than males. However, the mechanisms resulting in gender differences in multiple sclerosis are unknown. Activated microglia are believed to contribute to multiple sclerosis pathology, perhaps in part due to production of nitric oxide (NO) and TNF-alpha, molecules which can be toxic to cells including oligodendrocytes. The current study demonstrates that the female sex steroids estriol, beta-estradiol and progesterone inhibit lipopolysaccharide (LPS) induction of nitric oxide (NO) production by primary rat microglia and by the mouse N9 microglial cell line. These hormones act by inhibiting the production of inducible nitric oxide synthase (iNOS) which catalyses the synthesis of NO. Estriol likely inhibits iNOS gene expression since the hormone blocks LPS induction of iNOS RNA levels. The pro-inflammatory cytokines IFN-gamma and TNF-alpha are believed to be important modulators of multiple sclerosis. Here, we demonstrate that estrogens and progesterone also inhibit NO production by microglial cells activated in response to these cytokines. Activated microglia elicit TNF-alpha in addition to NO and we further demonstrate that estrogens and progesterone repress TNF-alpha production by these cells. Finally, estriol and progesterone, at concentrations consistent with late pregnancy, inhibit NO and TNF-alpha production by activated microglia, suggesting that hormone inhibition of microglial cell activation may contribute to the decreased severity of multiple sclerosis symptoms commonly associated with pregnancy.

Animals↗