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PubMed1976

Toxemia of pregnancy: assessment of fetal distress by urinary estriol and circulating human placental lactogen and alpha-fetoprotein levels.

The efficacy of three biochemical methods for the detection of fetal distress was assessed in a prospective study of 224 singleton pregnancies complicated by toxemia. Fetal distress was diagnosed in 65 cases (29 per cent). Abnormally low urinary estriol (E3) excretion pointed out 63 per cent, low serum levels of human placental lactogen (HPL) 27 per cent, and elevated maternal serum alpha fetoprotein (AFP) 10 per cent of distressed fetuses. The efficacy of each test increased with the severity of maternal disease. The frequencies of false pathologic levels were: E3 19 per cent, HPL 0 per cent, and AFP 1 per cent of the cases with a normal fetal outcome. Although E3 was by far the most effective marker, abnormal levels of HPL and AFP provided supportive evidence for fetal distress by pointing out those cases in which E3 reading was not a false positive.

Eclampsia↗

PubMed1977

Unconjugated estriol and 15alpha-hydroxyestriol in complicated pregnancies.

Simultaneous determinations of unconjugated estriol and 15alpha-hydroxyestriol (E4) levels in maternal serum were studied serially to ascertain the relative usefulness of these estrogens as indicators of fetal welfare. Complicated pregnancies included 16 patients with pre-eclampsia and/or hypertension, six patients with severe Rh-isoimmunization, 12 patients with diabetes mellitus, of which four had vascular disease, three patients with fetal death in utero, and three twin pregnancies. Retrospective analysis failed to indicate a clinically useful role for serum E4 determinations in the evaluation of fetal welfare during high-risk pregnancies.

Antibody Formation↗

PubMed1978

Study of the kinetics of conversion of maternal plasma dehydroisoandrosterone sulfate to 16 alpha-hydroxydehydroisoandrosterone sulfate, estradiol, and estriol.

The transfer constants of conversion of maternal plasma dehydroisoandrosterone sulfate to estradiol ([rho]DS-E2BU) and to 16alphaOH-dehydroisoandrosterone sulfate ([rho]DS-160HDS BU) and of maternal plasma 16alphaOH-dehydroisoandrosterone sulfate to estriol ([rho]160HDS-E3 BU) were measured in women late in pregnancy. The mean [rho]160HDS-E3 BU, 0.17, was considerably less than the mean [rho]DS-E2 BU, 0.29. However, the extent of 16alpha-hydroxylation of maternal plasma dehydroisoandrosterone sulfate was great, the mean [rho]DS-160HDS BU being 0.36.

Dehydroepiandrosterone↗

PubMed1979

Circadian rhythms in maternal plasma cortisol, estrone, estradiol, and estriol at 34 to 35 weeks' gestation.

In order to examine the relationship between circadian rhythms in different steroids, cortisol (F), estrone E1), estradiol (E2), and estriol (E3) were measured by radioimmunoassay in maternal venous plasma taken at 30 to 60-minute intervals over 24 hours from 11 healthy women at 34 to 35 weeks' gestation. Maternal F was maximal at 0730 hours and fell significantly to its lowest concentration at 0230 hours. Maretnal E3 was lowest between 1000 and 1130 hours and rose significantly to maximal values between 2230 and 0030 hours. Maternal E1 was maximal between 1000 and 1130 hours and showed a significant decrease to reach its lowest concentration at 0430 to 0630 hours. No significant circadian change was measured in uncorrected concentrations of E2. We conclude that there is an inverse relationship between maternal F and E3, which would be consistent with a maternal effect on fetal adrenal function, and the existence of circadian rhythms in F, E1, E2, and E3 must be taken into account in clinical investigations of these hormones during pregnancy.

Circadian Rhythm↗

PubMed1979

Oxytocin challenge test results compared with simultaneously studied serum human placental lactogen and free estriol levels in high-risk pregnant women.

Three perinatal health indicators (serum human placental lactogen [hPL] levels, serum free estriol [E3] levels, and OCT) were simultaneously completed in 149 high-risk women who were more than 34 weeks pregnant. There was a significant correlation between the hPL and E3 results (r = 0.28, p less than 0.01). There was a 15.4% positive OCT result rate and the blood hormone values for the negative and positive OCT groups were compared. There was a significantly lower hPL value in the positive OCT group (4.7 +/- S.E.M. 0.4 vs. 6.2 +/- S.E.M. 0.2 micrograms/ml for positive and negative groups, respectively), whereas the free E3 levels were not different in these two OCT groups (14.8 +/- S.E.M. 1.5 vs. 16.3 +/- S.E.M. 0.7 ng/ml for positive and negative groups, respectively). The free E3 value did not help in predicting the OCT result as the low free E3 subgroup had the same frequency of positive OCT result as did the over-all group. There was a highly significant increase in the positive OCT results (42.9%) in women with a low hPL value (p less than 0.01). In those women with an hPL value of 6.0 microgram/ml or more there were only 8% positive OCT's. It is concluded that on hPL test at about 34 weeks of gestation could be used to screen pregnant women, and if the value were low (less than 4.0 microgram/ml) an OCT evaluation test would be indicated, for there is a very high frequency of positive results in that subgroup of women.

Estriol↗

PubMed1980

Serum progesterone, estradiol, and estriol before and during induced labor.

To investigate the association of serum levels of progesterone (P), estradiol (E2), and estriol (E3) with the initiation of regular contractions, venous blood samples were taken prior to and 3 hours after the successful induction of labor in 83 parturients by means of low amniotomy and intravenous oxytocin infusion. The serum P level and P/E2 ratio decreased and serum E2 level increased after induction in healthy primigravidas and in parturients with an initial P dominance (serum P/E2 ratio more than 5). There was also a decrease in the serum P level and P/E2 ratio in postterm patients and parturients with a ripe cervical state. Cholestasis of pregnancy was associated with a rise in the serum level of E2 and a decrease in the P/E2 ratio. In an unfavorable cervical state there was a rise in the serum E2 level; patients with an initial E2 dominance (serum P/E2 ratio 5 or less) showed a rise in the serum P level and P/E2 ratio. Healthy multigravidas and patients with pre-eclampsia did not show any hormonal changes. The onset of induced labor seems to be associated with a rise in serum E2 concentration and/or with a drop in P concentration. The increase in serum E2 level is thought to be due to the activation of the anterior pituitary--adrenal axis. The lower P level is supposedly a result of diminished uteroplacental circulation.

Cervix Uteri↗

PubMed1981

Loss of diurnal rhythm in plasma estrone, estradiol, and estriol in women treated with synthetic glucocorticoids at 34 to 35 weeks' gestation.

In order to examine the effect of endogenous rhythms in fetal and/or maternal adrenal activity on diurnal changes in plasma estrone (E1), estradiol (E2), estriol (E3), and progesterone (P) in women at 34 to 35 weeks' gestation, we measured these steroids in a group of six women in whom the endogenous circadian rhythm in cortisol was absent or had been suppressed by treatment with exogenous synthetic glucocorticoids. All steroids were suppressed, and no diurnal rhythms in E1, E2, E3 or P were found. Suppression of cortisol and estrogens was greater after dexamethasone (Dx) than after a glucocorticoid-equivalent dosage of prednisone (Pd). Loss of the maternal estrogen rhythms seen in normal patients is consistent with the suggestion that such rhythms may be attributable to diurnal changes in maternal and/or fetal adrenal output of potential precursors. The differences in cortisol and estrogen concentrations after Dx and Pd may indicate dissociation of the glucocorticoid (hyperglycemic) and adrenocorticotropic hormone-suppressing activities of these compounds.

Adrenal Glands↗

PubMed1993

Maternal serum screening for alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin between 11 and 15 weeks of pregnancy to detect fetal chromosome abnormalities.

OBJECTIVE: The purpose of this prospective study was to assess the value of maternal serum screening between 11 and 15 weeks of gestation to detect fetal Down syndrome. STUDY DESIGN: Blood samples were collected on 993 women between 11 and 15 weeks' gestation before amniocentesis. Ninety percent were > or = 35 years old. Samples were coded and assayed for alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin. Medians were established at each week between 11 and 15 from 836 normal, singleton pregnancies. RESULTS: We used a computer-generated cut-off risk for Down syndrome of one in 365 at term; nine of 11 (82%) Down syndrome pregnancies were identified. There were 23% false-positive results in women > or = 35 years old and 6% in those < 35 years. CONCLUSION: These results suggest that maternal serum screening between 11 and 15 weeks may provide an acceptable alternative to screening between 16 and 20 weeks.

Chorionic Gonadotropin↗

PubMed1995

A prenatal trisomy 21 screening program using alpha-fetoprotein, human chorionic gonadotropin, and free estriol assays on maternal dried blood.

OBJECTIVE: The feasibility of large-scale Down syndrome maternal screening with dried blood samples and nonradioactive methods was examined. STUDY DESIGN: A prospective observation study was performed on a nonselected population of 11,241 pregnant women sampled between January 1991 and September 1992, between 14 and 24 weeks' gestation (ultrasonographic scanning available for 91.6%), through a multicenter collaborative network. Enzyme-linked immunosorbent assays for alpha-fetoprotein, human chorionic gonadotropin, and free estriol were performed on dried blood samples. Risk determination was made with an in-house software implementing the multivariate gaussian log likelihood method. RESULTS: A total of 10,450 samples were eligible for the study. Mean age at term was 27.9 years. A total of 6.84% of the patients were > or = 35 years old with a prior risk of trisomy 21 > 1:350. The general positive rate of our sample was 8.15%. After calculation 31.7% with prior risk > 1:350 were still in the high-risk group; 6.36% of the low-risk group were found to be at high risk for Down syndrome. Fifteen trisomic pregnancies were observed, of which 11 had a calculated risk higher than the selected cutoff value (1:350). The overall detection rate was 73%, specificity was 92%, and positive predictive power was 1.2%. CONCLUSION: Our pilot study has shown performances within the range of conventional serum screening programs. Dried blood assays are a handy alternative to serum assays. Blot paper cards represent a simple method of sampling, well fitted for large population screening. Combined with nonradioactive methods, this method appears to be both low cost and effective. The current work apparently is the first large-scale Down screening program performed with dried blood.

Adult↗

PubMed1995

Triple marker (alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin) versus alpha-fetoprotein plus free-beta subunit in second-trimester maternal serum screening for fetal Down syndrome: a prospective comparison study.

OBJECTIVE: Our purpose was to compare the efficacy of triple-marker screening (alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin) with alpha-fetoprotein plus free beta-human chorionic gonadotropin. STUDY DESIGN: Free beta-human chorionic gonadotropin was concurrently assayed in 2349 maternal serum samples. Trivariate and bivariate algorithms were used to calculate the risk for fetal Down syndrome by the two protocols. Free beta-human chorionic gonadotropin from 12 cases of fetal Down syndrome previously screened with the triple marker was retrospectively assayed. RESULTS: Mean maternal age of our study was 29.8 years (range 14 to 51 years). The initial screen-positive rate with the triple marker was 8.0% compared with 12.8% for alpha-fetoprotein plus free beta-human chorionic gonadotropin. All three cases of fetal Down syndrome ascertained in our prospective study were detected by the triple marker; in contrast, one of three was detected by alpha-fetoprotein plus free beta-human chorionic gonadotropin. By adding 12 additional cases of fetal Down syndrome, 12 of 15 (80%) were screen positive with triple marker and nine of 15 (60%) were screen positive with alpha-fetoprotein plus free beta-human chorionic gonadotropin. CONCLUSION: The detection rate of fetal Down syndrome was greater by use of a triple marker screen than when using alpha-fetoprotein plus free beta-human chorionic gonadotropin. Our data do not support the claims of other studies that suggest that alpha-fetoprotein plus free beta-human chorionic gonadotropin is superior to triple markers.

Adolescent↗

PubMed1976

Rapid determination of urine estriol by an on-column derivatization procedure.

Estriol in pregnancy urine is determined by acid hydrolysis of steroid conjugates, followed by ether and aqueous sodium hydroxide extraction and gas chromatography. Derivatives are formed within the injection port of the gas chromatograph using tetramethylammonium hydroxide. Several samples may be processed simultaneously. Hydrolysis and extraction of a specimen are done in a single culture tube; for larger numbers of specimens, a Paton-Brown extractor may be used. With a two-column gas chromatograph, results on two specimens are available within one hour; twelve analyses may be completed within two hours.

Chromatography, Gas↗

PubMed1982

Ovulation prediction: changes in the concentrations of urinary estrone-3-glucuronide, estradiol-17 beta-glucuronide and estriol-16 alpha-glucuronide during conceptional cycles.

The concentrations of estrone-3-glucuronide (E1-3-G), estradiol-17 beta-glucuronide (E2-17 beta-G), estriol-16 alpha-glucuronide (E3-16 alpha-G) and LH/hCG have been measured in daily samples of early morning urine from six women who conceived during the period study. The specimens were collected from the second day of menstruation until the values for hCG were greater than 200 U/l. The aim of the study was to assess which of the metabolites should be measured preferentially to predict ovulation by 72 h and hence identify the probable start of the fertile period. The peak of LH was used as a reference point for ovulation and defined as Day 0. A defined rise (50% increase over the mean of three preceding values) in the concentration of each steroid metabolite occurred on the following days (mean and range): E1-3-G Day LH-4.7 (-3 to -6), E2-17 beta-G Day LH-3.7 (-3 to -6) and E3-16 alpha-G Day LH-4.5 (-3 to -6). The concentration (nmol/l; mean and range) of each metabolite on the day of the rise was: E1-3-G (106; 78-137), E2-17 beta-G (19; 5 to 27) and E3-16 alpha-G (28; 18-40). It is concluded that the measurement of each estrogen glucuronide provides similar information and quantitatively E1-3-G is the most important.

Adult↗

PubMed1983

Algorithmic analysis of estriol time concentration curves as a guide to timing of amniocentesis for fetal lung maturity.

Utilizing a computerized algorithm which estimates gestational age (GA) by analyses of third trimester plasma estriol (E3) concentration curves, we predicted L/S ratios at the time of 64 amniocentesis indicated for assessment of fetal maturity. In the identification of immature fetuses, both methodologies concur in 95% of cases if an L/S ratio of less than or equal to 2.3 and projected GA of less than or equal to 36 weeks are accepted as cut-off points. In the identification of mature fetuses there is agreement in only 54% of cases if an L/S ratio of greater than or equal to 2.3 and projected GA of greater than or equal to 37 weeks are accepted as cut-off points. The data show that the E3 algorithm is of value in the postponing of premature and therefore unnecessary amniocenteses for fetal maturity. However the poor correlation between the E3 algorithm, a method previously shown to be accurate in GA prediction, and mature L/S ratios demonstrates the need to utilize more accurate indicators of mature amniotic fluid surfactant activity in future investigations.

Amniocentesis↗

PubMed1984

Relative distribution of estrone, estradiol and estriol between fetal and maternal perfusates during perfusions of human term placentas with labelled C19 precursors.

Published results from in vivo experiments carried out in Rhesus monkeys and from in vitro perfusions of human term placentas have indicated that placental estradiol (E2) is preferentially released towards the mother whereas estrone (E1) is about evenly distributed between fetal and maternal circulation. In order to examine the distribution of estriol, relative to that of E1 and E2, we have now prepared [3H]16-hydroxyandrostenedione by incubation of [6,7-3H]androstenedione with Streptomyces roseochromogenus and perfused placental cotyledons with mixtures of these two labeled precursors. Measurement of the concentrations of tritiated E1, E2 and E3 in the maternal and fetal perfusates, flowing at approx 10 and 5 ml/min, respectively, indicated that the distribution of E3 is different from that of E2 and resembles the distribution of E1. The simple perfusion system being used shows differences in the distribution of various estrogens between fetal and maternal perfusates which may reflect the in vivo situation and offers the opportunity for experimental examination of various explanations for these differences, e.g. existence of specific carrier systems in the syncytial membranes, specific binding of the estrogens to secreted placental proteins, and actions of placental and decidual 17 beta-hydroxysteroid dehydrogenases.

Androstenedione↗

PubMed1984

RU 16117, an orally active estriol-like weak estrogen.

RU 16117, the 11 alpha-methoxy derivative of ethynyl estradiol, is an orally active weak estrogen potentially effective in the treatment of estrogen-deficiency in postmenopausal women (climacteric symptoms and severe osteoporosis). Biochemical studies have shown that RU 16117, like estriol, possesses the properties characteristic of a partial estrogen agonist/antagonist. RU 16117 binds to the cytosol estrogen receptor (ER) to form a complex which dissociates much faster than the estradiol complex. This explains its lower nuclear uptake. Furthermore, the nuclear RU 16117 complex also dissociates faster than the estradiol complex. Consequently, although low doses of RU 16117 can induce the majority of the effects of estradiol (increased polymerase A and B activities, cytosol ER replenishment, progestin receptor induction, increased uterine weight), these effects are long-lived only if the dose is considerably increased or if the compound is administered repeatedly or continuously. Since RU 16117 transiently occupies available estrogen binding sites, it can prevent the full response of estradiol. Thus, under appropriate kinetic conditions, it acts as an estrogen antagonist on the above parameters and also on DMBA-induced mammary tumors in the rat. At a daily dose of 24 micrograms for a period of 4 weeks RU 16117 led to 65% reduction in the number of already-established tumors. RU 16117 inhibits basal gonadotropin secretion and decreases the LH response to LHRH. Injection of 5 micrograms s.c. to the rat in estrus markedly inhibited the spontaneous peaks of LH, FSH and PRL measured on the afternoon of expected proestrus. Low doses which block ovulation by 100% had no detectable effect on vaginal cornification, thus suggesting a greater sensitivity at the hypothalamo-pituitary level.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1984

Estriol and estradiol interactions with the estrogen receptor in vivo and in vitro.

The cytosolic estrogen receptor (calf uterus) bound to estradiol (E2) at 0 degrees C changes from a state with fast into a state with slow E2 dissociation rates when placed at 28 degrees C. This temperature accelerated transition in receptor affinity for its ligand takes place within 10 min at 28 degrees C. Similarly, receptor bound to estriol (E3) at 0 degrees C changes, when heated, from a state with fast into a state with slow E3 dissociation. The main difference between RE2 and RE3 was that E3 dissociates from unheated 8S RE3 and heat-transformed 5S RE3 at a much faster rate than E2 from RE2 . In the mature ovariectomized rat a slow dissociating 5S receptor estrogen complex is found in nuclei 1 h after injection of [3H]E2 or [3H]E3. In vitro dissociation of these 2 estrogens from this nuclear bound receptor formed in vivo takes place at rates similar to those from heat-transformed cytosolic RE2 or RE3 complexes. Addition of pyridoxal 5'-phosphate (PLP) to the slow-dissociating heat-transformed 5S estrogen receptor complexes causes rapid dissociation of E2 or E3; this effect is dose-dependent and is not due to disruption of 5S dimers, since after PLP addition RE2 and RE3 sediment unchanged as 5S dimers. The presence of a large excess of non-radioactive 4S RE3 does not interfere with the temperature induced rapid transition of 4S R[3H]E2 complexes from the state with fast into a state with slow E2 dissociation kinetics. A model is presented to explain the temperature induced biphasic estrogen dissociation from the receptor. It is proposed that the low affinity 4S RE2 monomer undergoes a temperature and estrogen dependent conformation change, such that the ligand is "locked" into the receptor's binding site. This conformational change results in the formation of a high affinity 4S monomer from which estrogen dissociates at a slower rate. This reaction is independent from subsequent 4S to 5S dimerization (transformation). The different rates of ligand dissociation from the low and high affinity 4S receptors reflect the different interactions (hydrophobic and hydrogen bonding) of E2 and E3 with the estrogen binding domain.

Animals↗

PubMed1984

Estriol in human breast cyst fluid.

Although cystic lesions of the breast are not precancerous per se, statistical studies have indicated that this condition predisposes a 2- to 4-fold greater risk for breast cancer. Seeking a hormonal etiology to this correlation, investigators have analyzed breast cyst fluid ( BCF ) for steroids and have compared the levels to those in the blood. The 17-ketosteroids-androsterone, dehydroisoandrosterone and their sulfates are elevated in BCF . The same is true for estrone sulfate and estradiol-3-sulfate. We have found the most dramatic differences with estriol-3-sulfate (E3-3S), the concentration of which ranged from 187-6134 pg/ml in over 40 specimens analyzed, whereas in 12 serum specimens from normal women, E3-3S was barely detectable. The origin of E3-3S is not known. [3H]E3-3S is not concentrated in BCF following its injection into an arm vein. The blood half-life of [3H]E3-3S is much lower than that of estrone sulfate. Samples of breast nipple aspirates from normal women were also analyzed for E3-3S. None could be detected. The best explanation of the data accumulated thus far is that E3-3S is synthesized at the epithelial lining of the cyst and released into the BCF , from which its efflux is inefficient.

Adult↗

PubMed1984

Binding of estradiol-17 beta and estriol in cytosolic and nuclear fractions from urogenital tissues.

This report describes the measurement and partial characterization of the specific binding of estradiol (E2) and estriol (E3) in the cytosols and nuclear fractions from uterus, vagina, urethra and urinary bladder of the rabbit. Fractions from uterine and vaginal tissues showed the highest binding with both E2 and E3 approx 300 fmol/mg protein. The levels of specifically bound E3 were about 70% of the corresponding values for E2. In the sedimentation analysis the cytosolic receptors for both E2 and E3 exhibited 2 major forms, 3 S and 8 S, in addition to the heavy aggregates. Sephacryl S-200 chromatography showed major and minor components corresponding to mol. wt of 250.000 and 20.000-40.000 respectively. No noteworthy differences in the cytosolic receptors from different tissues could be observed in the above analyses. Whereas the uterine nuclear E2 receptor sedimented at 4.3 S the vaginal receptor distributed in two peaks, 2.5 S and 4.3 S. The receptor from both urethra and urinary bladder sedimented at 2.5 S. Nuclear E3 receptor, however, showed a major peak at 3.5 S in all cases. Some differences in tissue nuclear receptor were also observed in their chromatographic behaviour. The results confirm the existence of estrogen receptor in both urethra and urinary bladder, and the data of the limited physiochemical analysis indicate that the receptors in these tissues are essentially similar to those in the uterus or vagina.

Animals↗