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PubMed1984

Biological responses and histological studies of estriol and estriol sulfate in fetal and newborn uteri of guinea pig.

The biological responses of estriol (E3) and of estriol-3-sulfate (E3-S) in the fetal and newborn uteri of guinea pig were studied. After a treatment of E3 (1 mg/kg/day) or E3-S (1.4 mg/kg/day) to pregnant guinea pigs (49-60 days of gestation) for 6 days, both estrogens provoke a significant uterotrophic effect in the fetal uterus which increases in weight 1.8-2.5 times in relation to the non-treated animals. The stimulation of progesterone receptor (PR) is also very intense, 7-12 times in relation to the control animals. In another series of experiments newborn guinea pigs (2-day old) were treated with 100 micrograms/animal of E3 or 140 micrograms/animal of E3-S for a short (2 days) or a long (12 days) period. Concerning the uterotrophic effect, the weight of the uterus increases 1.8-2.5 times (in relation to the non-treated animals) after a 2-day treatment and the effect continues to increase up to 4-5 times in the 12-day treated animals. In opposition to the fetal uterus, the effect on PR provoked by E3 or E3-S is very limited (only an increase of 1 time in relation to the non-treated animals); the effect is even less intense after the 12-day treatment. Histological studies show an intense hypertrophic effect particularly in the epithelium of the endometrium in the fetal and newborn uteri for both E3 and E3-S. In the newborns the effect is also intense on the epithelium of the uterine gland. It is concluded that: (1) Estriol and estriol sulfate are very active and with similar intensity on the uterine weight before and after birth; (2) The stimulatory effect on PR decreases very significantly after birth and after a long treatment; (3) E3-S can act as a potent hormonal precursor.

Animals↗

PubMed1976

Effect of ampicillin administration on estradiol, estriol, and cortisol levels in meternal plasma and on estriol levels in urine.

Ampicillin treatment in the last trimester of pregnancy had no significant effect on the levels of estradiol, estriol, or cortisol in maternal plasma. Urinary estriol excretion was, however, notably decreased during or following ampicillin treatment in six out of 10 patients. These results suggest that the plasma estrogen assays have greater validity than the urinary estriol assay in assessing fetoplacental endocrine function during a period of ampicillin treatment of the mother.

Ampicillin↗

PubMed1993

The synthesis of estriol 16- and 17-monoglucuronide from estriol.

An efficient and convenient procedure for the synthesis of estriol 16- and 17-monoglucuronides from estriol is described. This is achieved by the selective protection and deprotection of the hydroxy groups in estriol, Koenigs-Knorr reactions with methyl 1-bromo-1-deoxy-2,3,4-tri-O-acetyl-alpha-D-glucopyranuronate and subsequent hydrolysis. The products have been characterized by proton nuclear magnetic resonance (1H NMR), two-dimensional 1H homonuclear shift-correlated spectra (2D-COSY) and mass spectra. The selective Koenigs-Knorr reaction of the alcoholic hydroxyl group in the presence of a phenolic hydroxyl group is also reported.

Estriol↗

PubMed1985

Screening in pregnancy with unconjugated estriol compared with total estriol.

An obstetric population was screened 'blind' by measuring unconjugated estriol (ucE3) and total estriol (tE3) in serum. The purpose was firstly to ascertain the predictive values of ucE3 for the prediction of low birth weight and distressed neonates (perinatal deaths included), and secondly to compare the predictive values of ucE3 and tE3. The main material consisted of 1018 singleton pregnancies with known term, who would not have undergone estriol (E3) measurement had it not been for this investigation. The study was carried out prospectively, and the obstetricians had no knowledge of the E3 values in the screened pregnancies. When at least one of the ucE3 values was low, the risk of having a small for gestational age (SGA) infant was 22%. Low tE3 implied a 27% risk. When both were low, the risk of a SGA infant was 54%. The percentages of SGA infants found were 18, 19, and 12%, when ucE3, tE3, or both respectively, were low. ucE3 does not appear to be superior to tE3. From the predictive values found in this study, screening of a total obstetric population with ucE3 and/or tE3 cannot be recommended.

Adult↗

PubMed1975

Direct radioimmunoassay for unconjugated estriol in pregnancy serum, with use of a radioiodinated derivative of estriol.

We describe a rapid and direct 125I-based radioimmunoassay for quantification of unconjugated (free) estriol in pregnancy serum. Estriol in serum is adsorbed onto a small column of Sephadex, thereby allowing its separation from proteins and interfering materials. A radioiodinated derivative of estriol (6-ketoestriol-6(o-carboxymethyl)oxime-[125I]tyrosine methyl ester) is added to the column, followed by a limiting amount of antiserum. After incubation, the antibody-bound hormone is separated by a buffer wash. The assay exhibits satisfactory recovery and parallelism, and the intra- and inter-assay coefficients of variation are less than 10%. The values obtained by using the assay correlate well (r = 0.97) with those from a comparison method in which solvent extraction and chromatographic purification are used.

Cross Reactions↗

PubMed1985

[Studies on changes in serum estrone, estradiol, estriol, DHA-S, and cortisol and urinary estriol excretion].

Radioimmunoassay was used in order to investigate changes in steroid hormone, serum estrone, estradiol, estriol, dehydroepiandrosterone-sulfate (DHA-S) and cortisol in 71 cases of twin pregnancies. Also, urinary estriol was measured by the Amberlite XAD-2 method. These results were compared with those in 90 cases of single pregnancies. In the third trimester, the increase in serum estrogen levels in twin pregnancies was significantly higher than that in single pregnancies. From 28 to 34 weeks of pregnancy, the DHA-S level in single pregnancies rapidly dropped and after that, gradually decreased to the base level. But in the other weeks of pregnancy, no change in DHA-S was observed. The serum cortisol level in twin pregnancies was slightly higher than in single pregnancies. There was no significant difference between them. The nse in the cortisol level in twin pregnancies was significantly greater than in single pregnancies after 38 weeks of pregnancy. The urinary estriol level in twin pregnancies was significantly higher than in single pregnancies and had values 1.8-3.0 times higher than in single pregnancies.

Adult↗

PubMed1984

Salivary estriol concentrations during normal pregnancies, and a comparison with plasma estriol.

Saliva would have advantages over plasma or urine for monitoring estriol during pregnancy. Specimen collection, after stimulation of flow by citric acid, is non-invasive and simple. We measured concentrations of unconjugated estriol in saliva and compared them with those in plasma in normal pregnancies, and found a good correlation (r = 0.79). In addition, trends of concentrations in saliva and plasma were statistically compared and found to be highly correlated. The variation among individuals in the saliva/plasma concentration ratio suggested that some inter-individual factor(s) may affect this relationship. The normal reference interval for unconjugated estriol concentration in saliva from 20 weeks of gestation to term was established.

Estriol↗

PubMed1999

Simultaneous determination of estriol and estriol 3-sulfate in serum by column-switching semi-micro high-performance liquid chromatography with ultraviolet and electrochemical detection.

A column-switching HPLC with semi-microcolumn enabled us a direct and simultaneous analysis of estriol (E3) and estriol 3-sulfate (E3 S) in human serum in combination with ultraviolet (for E3 S) and electrochemical (for E3) detectors. The mobile phases (phosphate buffer pH 7.0) contained 5 mM tetra-n-butylammonium ion (TBA) as a counter ion for E3 S. Serum samples were diluted with 200 mM phosphate buffer (pH 7.0) containing 100 mM TBA, then injected to the pre-column. After serum proteins had flowed out from the pre-column, E3 and E3 S were transferred to the enrichment column. Subsequently the analytes were eluted to the analytical column. Detection limits of E3 and E3 S in human serum were 2.5 ng/ml and 295 ng/ml. Serum E3 and E3 S levels (mean +/- SD) of umbilical artery from 18 full-term healthy neonates were 33+/-23 ng/ml and 1.26+/-0.69 microg/ml, respectively.

Calibration↗

PubMed1981

On the occurrence and transport of estriol-3-sulfate in human breast cyst fluid: the metabolic disposition of blood estriol-3-sulfate in normal women.

The high concentration of estriol-3-sulfate (E3-3S) in human breast cyst fluid has been confirmed in 14 women with multiple cysts. The concentrations of E3-3S found in individual cysts drained within a short time span from the same patient were variable, the ratios ranging from unity to 40. After the iv administration of [14C]estriol or [3H]E3-3S, only minor accumulation of either isotope was detected in the cyst fluids aspirated 6.5-30 h later. Since surprisingly small amounts of isotopes were found in blood, the metabolism of [3H]E3-3S was studied in 2 normal women. The test compound was injected iv, and blood samples were taken at intervals up to 7.5 h. In addition, total urine was collected for 3 days. The blood clearance of [3H]E3-3S was rapid, with the half-life ranging from 15-30 min. However, E3-3S was only a minor component of the urine, indicating rapid tissue extraction and metabolism rather than renal excretion for the compound. The studies indicate that E3-3S of human breast cyst fluid does not equilibrate rapidly with other body pools and that its uptake, if any, from the blood would be against a gradient.

Adult↗

PubMed1975

[Excretion of estriol, estetrol, 16-epi-estriol, 16-keto-estradiol and 16-hydroxyestrone in the 24-hour urine of pregnant women in the last trimester].

In this publication a method is given which allows simultaneous estimation of estriol, estetrol, 16-epiestriol, 16-ketoestradiol and 16-hydroxyestrone in urine of pregnant women. First conjugates are precipitated with ammoniumsulfate and hydrolyzed. Then the steroids are extracted and converted to azodyes by reacting with the diazonium salt dark blue r. After separation by thin layer chromatography the azodyes are measured by remission analysis with a chromatogramm spectrophotometer. From the data obtained from 66 cases norm groups were set up for the excretion of the steroids in the 3rd trimester of pregnancy. In the last month of pregnancy the average excretion, expressed in % of excreted estriol, is as follows: estetrol 5,7%, 16-epiestriol 3,1%, 16-ketoestradiol 7,0%, 16-hydroxyestrone 5,3%.

Adult↗

PubMed1979

Plasma levels of unconjugated estetrol and estriol and of total estriol in normal human pregnancy.

The course of normal pregnancy in 54 patients was monitored by weekly assays of Unconjugated Estriol (E3U), Total Estriol (E3T) and Unconjugated Estetrol (E4U). These subjects were divided into two groups: one of those patients who delivered a fetus with a weight above the 50th percentile and the other of those who delivered a fetus with a weight below the 50th percentile. No significant difference was found between these two groups and it is not therefore possible to have information regarding the weight of the fetus, starting from the weekly values of these hormones. Analogous variations of the three hormones were found as pregnancy progresses. However, the rate of increase for E4U was higher than for E3T and E3U.

Adolescent↗

PubMed1987

Ontogeny of unconjugated estriol in fetal blood and the relation of estriol levels at birth to the development of respiratory distress syndrome.

Unconjugated estriol (E3) was quantified in serum of umbilical cord blood of 533 newborn infants, 360 of whom were delivered between 23 and 37 wk of gestation. Serum E3 levels rose (F = 7.71, p less than 0.0001) as a function of gestational age; the mean concentration of E3 at 37.5-42 wk of gestation (105 ng/ml, n = 173) was significantly higher than that in serum of newborns delivered at 23-28 wk of gestation (63 ng/ml, n = 33). Umbilical cord serum levels of E3 were significantly higher among newborns delivered vaginally between 31.5 and 42 wk of gestation than among newborns delivered by cesarean section (p less than 0.005). Although serum E3 levels correlated highly (p less than 0.0001) to newborn weight throughout the entire period of gestation, there was no relationship of newborn weight to umbilical serum E3 levels within a given gestational period. Also, the umbilical serum levels of E3 in male infants were similar to those of female infants at each gestational age. Significant changes in umbilical serum levels of E3 as a function of gestational age were not observed among newborns (n = 90) who developed respiratory distress syndrome (RDS). The mean umbilical serum concentration of E3 in newborns delivered at 34.5-37 wk of gestation who developed RDS were significantly lower (p less than 0.01) than that in similar aged newborns whose lung function was normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗

PubMed1985

Interaction of estradiol and estriol with uterine estrogen receptor in vivo and in excised uteri or cell suspensions at 37 C: noncooperative estradiol binding and absence of estriol inhibition of estradiol-induced receptor activation and transformation.

The partial agonist and antagonist properties of estriol (E3) have been related to the brief nuclear retention of receptor-E3 complexes and to the lower affinity of E3 for the receptor compared to estradiol (E2). More recently, it was proposed that the partial agonist/antagonist activity of E3 may be due to its ability to eliminate positive cooperative binding of [3H]E2 to cytosolic estrogen receptor. In this model, positive cooperativity is related to receptor activation and transformation. We first examined the long term effects of E3 on E2 action in vivo. Mature ovariectomized rats were treated for 16 days with E2, E3, or mixtures of these two substances delivered through Alzet pumps at a constant hourly rate (E2, 0.04 microgram; E3, 0.4 and 0.04 microgram; E2 and E3, 0.04 and 0.4 microgram). The effects of E3 on uterine growth, induction of progesterone receptor synthesis, and activation (nuclear binding) of estrogen receptor suggest that when given continuously, E3 acts as a full agonist and does not inhibit E2 action. Furthermore, incubation of uteri at 37 C with [3H]E2 in the presence of a 1- to 20-fold molar excess of nonradioactive E3 did not alter the subcellular distribution of receptor-[3H]E2 complexes (80% nuclear and 20% cytosolic), demonstrating that E3 does not inhibit E2-induced receptor activation (i.e. the increased nuclear binding of receptor). Similarly, 4S to 5S transformation of [3H]E2-labeled estrogen receptor in intact uteri was not inhibited by E3. Equilibrium binding of [3H]E2 to uterine cell suspensions at physiological temperature (37 C) was noncooperative; nonradioactive E3 did not alter the affinity of the estrogen receptor for [3H]E2; Dixon plot analysis indicates that E3 is a purely competitive inhibitor of [3H]E2 binding. This, in conjunction with the lower affinity of the receptor for E3 than for E2, adequately explains the agonistic-antagonistic properties of E3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Saliva estriol measurements: an alternative to the assay of serum unconjugated estriol in assessing feto-placental function.

We have investigated the possibility of replacing measurements of maternal serum estriol (E3) with maternal saliva E3. Saliva and serum E3 concentrations were measured by RIA in samples obtained from normal subjects in late pregnancy. The saliva E3 was found to accurately reflect the serum unbound unconjugated E3 and was directly proportional to total serum unconjugated E3. The variability in saliva E3, as assessed by the coefficient of variation for samples collected at intervals of 1 day, 1 h, or 10 min (16.5%, 22.7%, and 13.1% respectively) was not significantly different from published data on the variability in serum E3. No diurnal variation was apparent in samples collected every hour throughout the waking period of a normal day (n = 23). The increase in saliva E3 with gestational age was consistent with the well established pattern for serum E3, with the median value exhibiting a small but significant rise between 32 and 33 weeks and a larger rise between 36 and 37 weeks. The ease with which saliva samples may be collected procedure together with the high correlation between saliva and serum unconjugated E3 levels suggest that assay of saliva E3 should replace serum E3 measurement for assessing feto-placental wellbeing.

Animals↗

PubMed1983

Unconjugated estradiol, estriol and total estriol in maternal peripheral vein, cord vein, and cord artery serum at delivery in pregnancies with intrauterine growth retardation.

The levels of unconjugated estradiol (E2), estriol (E3) and total (conjugated plus unconjugated) E3 in maternal vein serum during labor, cord vein serum, and cord artery serum were measured in normal singleton and twin pregnancies with appropriate for dates babies (AFD) and with light for dates babies (LFD). The mean level of total E3 in the maternal vein serum in singleton pregnancy was significantly lower in the LFD group than in the AFD group, but no differences were seen in the mean levels of unconjugated E2 or E3 between the groups. The concentration of unconjugated E2 in the maternal vein serum was significantly higher in the twin group with a large placenta than in the singleton group with a smaller placenta, while the concentration of total E3 in the case of twin pregnancy with LFD was lower than that in singleton pregnancy with AFD but not significantly. No difference in the concentration of total E3 was observed between the cord vein serum and cord artery serum. The present data suggest that the total E3 level in maternal vein serum may be used in evaluating fetal states such as intrauterine growth retardation.

Dehydroepiandrosterone↗

PubMed1983

Estriol screening in pregnancy. Prognostic value of total estriol in serum (E3) in an obstetrical population.

One thousand six hundred and sixty pregnancies were recorded in this investigation. In 1 042 women with singleton pregnancies and known term, measurements of the total serum estriol (E3) were made exclusively for the present study. The study was prospective, and the clinicians had no knowledge of the E3 values. Within the screened group a low E3 value entailed a 42% risk of delivering an infant with perinatal complications and a 27% risk of an infant small for gestational age (SGA). 7% of the infants with perinatal complications and 19% of the SGA infants were detected at the screening. In a sub-group of 800 pregnancies considered normal according to given criteria, a low E3 level involved a 27% risk of perinatal complications and a 15% risk of an SGA infant. Of these cases 4% and 14% respectively had been detected at the screening. It is concluded that the E3 level should be measured on wide indications, but that this test is of little value in pregnancies that are clinically quite normal. Thus, the benefit of screening all apparently normal pregnancies depends upon the extent and thoroughness of the clinical antenatal care.

Estriol↗

PubMed1981

Estriol in pregnancy. VII. Unconjugated plasma estriol in prolonged gestation.

This study was undertaken to determine the course of unconjugated plasma estriol (E3) concentrations after 40 weeks' gestation and to assess whether the latter may be used as a first-line test in the management of term pregnancies with poor dates and prolonged gestation. Plasma E3 was measured twice weekly in 134 women with well-dated pregnancies of 40 weeks or more and in 213 women with pregnancies of unverified age but believed to be in excess of 40 weeks from the last menstrual period. The obstetric management was based upon twice weekly determinations of urinary E3 and antepartum heart rate testing, but not all patients complied. Plasma E3 levels were not availabe for management of the patients. The results indicate that unconjugated plasma E3 levels are highest at 40 weeks' gestation and decline thereafter by 12% each week. Because of this slow decline, biweekly assays suffice. Increasing and plateauing serial plasma E3 levels reveal that a patient approaches term or has reached 39 to 41 weeks' gestation, respectively, whereas decreasing E3 concentrations indicate that the patient is well beyond 40 weeks, and that her fetus may be about to or has become postmature. Only seven of the 347 patients studied were delivered of a postmature infant. Their last plasma E3 levels ranged from 3.8 to 8.0 ng/ml, i.e., were below the 95% confidence limits established for normal term pregnancies. It was found that 73% of the 347 patients had plasma E3 levels of 12 ng/ml or more, and that all their pregnancies ended normally, except for three instances of presumed intrapartum fetal distress. However, in 19 (20%) of the other 27% of the 347 patients who had plasma E2 levels of less than 12 ng/ml, abnormal outcome was encountered: postmaturity (seven), fetal death (four), intrauterine growth retardation (three), malformations (two), or intrapartum fetal distress (three). These results allow the conclusion that twice weekly assays of unconjugated plasma E2 may be used as a first-line test in the management of prolonged gestation.

Congenital Abnormalities↗

PubMed1976

Estriol in pregnancy. IV. Normal concentrations, diurnal and/or episodic variations, and day-to-day changes of unconjugated and total estriol in late pregnancy plasma.

Normal values of unconjugated, total, and immunoreactive (measured without extraction) plasma estriol (E3) have been determined from radioimmunoassay data obtained in 217 uncomplicated third-trimester pregnancies. Small but significant diurnal variations in unconjugated and total plasma E3 have been observed in a study comprising 12 women who were hospitalized during late pregnancy for diabetes, toxemia, or placenta previa. The late morning decreases in unconjugated and the afternoon/evening decreases in total plasma E3 concentrations, averaging some 10 to 15 per cent, were overshadowed by considerable episodic fluctuations and may thus be clinically irrelevant. Day-to day changes of unconjugated and total plasma E3 concentrations in late pregnancy were similar and smaller than changes in urinary E3 measurements. The urinary E3/creatinine ratio, however, reducing inadequacies of 24 hour urine collections, varied less than unconjugated or total plasma E3. The data suggest that a decrease in unconjugated or total plasma E3 must exceed 40 to 45 per cent of the mean of the three preceeding determinations if it is to be considered a signal of fetal distress.

Activity Cycles↗