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A study of circadian rhythms of estriol secretion in the third trimester of gestation complicated by gestosis and intra-uterine growth retardation (IUGR).

The circadian changes in serum estriol concentration in the case of gestosis (at 30-36 weeks gestation) and intra-uterine growth retardation-IUGR (at 28-36 weeks) were examined. The control group consisted of pregnant patients without placental insufficiency at 26-34 weeks gestation. No circadian rhythms of estriol secretion was found in patients with gestosis and IUGR, whereas such a rhythm was confirmed in normal pregnancies. The evaluation of circadian changes in estriol concentration in the third trimester of gestation may be useful when diagnosing chronic placenta insufficiency.

Circadian Rhythm↗

Comparison of assay kits for unconjugated estriol shows that expressing results as multiples of the median causes unacceptable variation in calculated risk factors for Down syndrome.

We compared the performance of two methods for assaying unconjugated estriol in serum: the modified Amerlex third-trimester RIA kit, as used in seminal papers on unconjugated estriol in Down syndrome screening, and the new optimized Amerlex-M second-trimester kit. The significant difference between the results of each assay could cause unacceptable changes in the detection rate and false-positive rate of Down syndrome screening programs, especially if previously published values for estriol are used in the risk calculation. It is not possible to define new calculation parameters for every assay kit because new parameters will need to be defined every time kit changes occur, which would require a large collection of samples from Down syndrome pregnancies for standardization. Possible solutions to this problem are discussed.

Down Syndrome↗

The biosynthesis of D-ring fatty acid esters of estriol.

Biological esterification with fatty acids is a feature that is now known to be common to most steroids. The esterification of estradiol in the D-ring at the 17 beta-hydroxyl leads to a family of extremely active estrogens. Similarly, esterification of the weaker estrogen, estriol (E3), has an even greater impact on its hormonal potency. We have recently shown that synthetic long chain esters of E3 at either 16 alpha- or 17 beta- are highly potent estrogens. The estrogenic activity of the synthetic E3 esters led us to determine whether E3 is biologically esterified, and if so, to characterize the resulting esters. Incubation of E3 with rat lung, a tissue which is highly active in esterifying estradiol, produces a nonpolar metabolite which upon saponification is converted back into E3. There was no evidence for the formation of a diester. Purification by high performance liquid chromatography separates the non-polar metabolite into two peaks, one the C-16 alpha- (approximately 60%) and the other the C-17 beta-ester (approximately 40%). The two fractions were further purified and characterized; each is a mixture of fatty acid esters of E3. The composition of the C-16 alpha- and the C-17 beta-fatty acid esters of E3 is identical. The predominant fatty acids are arachidonate, 34%, palmitate, 26%, followed by oleate 14%, linoleate 13%, stearate 8%, and palmitoleate 5%. The similarity of the esters at C-16 and C-17 may indicate that the fatty acid precursor for the acyltransferase is the same for both hydroxyl groups. It may also suggest that the same enzyme esterifies both positions in the D-ring. Since synthetic estriol fatty acid esters are extremely potent and long-lived estrogens, the enzymatic esterification of estriol produces powerful estrogens with considerable physiological potential.

Animals↗

[Reference values for progesterone, beta-HCG, estriol and human placental lactogen in the 10th-16th weeks of pregnancy].

Progesterone, beta-hCG, estriol and hPL in sera from 745 pregnant women have been measured in weeks 10 to 16 of pregnancy. The determined reference intervalls included the 10th and 90th percentile. All confidence intervalls have been calculated for a probability level of 10 per cent. The following levels were determined during the concerning weeks of pregnancy: progesterone 32-165 nmol/l, beta-hCG 31.5-260 micrograms/l, estriol 0.04-4.94 nmol l, and hPL 0.03-2.65 mg/l. The levels of progesterone are increasing weakly with the rising weeks of pregnancy, but the levels of beta-hCG are going down continuously. The levels estriol and hPL are showing a marked growth.

Chorionic Gonadotropin↗

Evaluation of urinary estriol by latex agglutination inhibition reaction.

The urinary estriol values of a morning sample determined by a new semiquantitative method was correlated with the total 24 hour estriol excretion determined by colorimetric method on patients with normal and pathologic pregnancy. The correlation coefficient, calculated on 240 assays operated on urine samples obtained from 70 normal pregnant women, is highly significant statistically (P less than 0.001). The profiles of the serial assays, obtained by these two procedures on patients with pathologic pregnancy, show a very strong analogy. The Authors believe that such a method, just for its simple and rapid realization, may be applied alternatively to RIA assay or colorimetric method for the cases which are believed to be in need of rapid evaluation of estriol and/or when another method is unfeasible.

Colorimetry↗

[The follow-up of high risk pregnancies with the determination of estriol 16-glucuronid excretion. Second: Excretion in preeclampsia, post maturity, intrauterine growth retardation, diabetes, Rh incompatability and intrauterine fetal deaths (author's transl)].

The estriol 16-glucuronid excretion was determined in 186 urine samples in cases with preeclampsia, post maturity, pregnancies past the expected date of confinement, intra-uterine fetal deaths, congenital anomalies, Rhesus incompatability and diabetes mellitus. In groups with mild dystrophy, severe dystrophy, and intra-uterine fetal death, three zones of estriol 16-glucuronid excretion were determined. Zone 1 is suggestive of a possible fetal impairment. Zone 2 shows a high probability of fetal impairment and Zone 3 was considered as lethal zone suggestive of imminent intra-uterine fetal death. The degree of rhesus incompatability, disease of the fetus or of diabetogenic fetopathy was not recognizable by the estriol 16-glucuronid excretion.

Abnormalities, Multiple↗

Plasma estradiol window and urinary estriol glucuronide determinations for monitoring menotropin induction of ovulation.

The plasma estradiol response is maximal 8--10 hours following mentropin injection. To obtain closer control, a menotropin protocol using 5 PM--8 PM injections and 8 AM blood sampling with a plasma estradiol window of 1000--2000 pg/ml was evaluated with simultaneous calibration of a urinary estriol glucuronide radioimmunoassay. One hundred twenty-eight paired urine and plasma samples were assayed in 48 cycles. In 26 cycles with paired samples on the day of human chorionic gonadotropin (hCG) injection, there were no cases of severe hyperstimulation, 2 cases of moderate hyperstimulation, and 11 pregnancies (42% of cycles given hCG). A window of between 40 and 100 micrograms/day of urinary estriol glucuronide corresponded to the 1000--2000 pg/ml plasma estradiol window by regression analysis. The pregnancy and hyperstimulation rates were compared with those observed in protocols previously published. Radioimmunoassay of urinary estriol glucuronide is faster and simpler than radioimmunoassay of plasma estradiol.

Abortion, Spontaneous↗

Congenital malformations, abnormal glucose tolerance, and estriol excretion in pregnancy.

Study of 10,454 consecutive newborn infants showed that 4.1% had a major malformation and 6.5% had a minor malformation. The incidence of major fetal malformations was increased in stillborn infants (14.1%), neonatal deaths (36.7%), and dysmature infants (8.6%), and when there was maternal hypoglycemia (5.8%, hyperglycemia (5.8%), or subnormal urinary estriol excretion (9.8%). Minor malformations were associated with fetal dysmaturity (9.7%) and subnormal estriol excretion (8.8%). Abnormalities of maternal glucose tolerance and urinary estriol excretion were associated with specific types of major malformations. These data showed that hypoglycemia was as important as hyperglycemia in the etiology of fetal malformations.

Australia↗

Urinary estriol estimations in normal and abnormal pregnancies.

Urinary estriol estimations from 24-hour urine specimens were studied in 65 women in the course of normal pregnancies and compared to 18 analyses in women in whom fetal death had occurred. There is a significant difference in the levels of estriol excretion between these two categories. Serial studies were carried out on patients whose pregnancies ended in normal delivery and in patients whose pregnancies were complicated by eclampsia and by hypertension of various degrees of severity. A definite correlation between urinary estriol excretion and the health of the fetus in utero was found. The information that these estimations provide can be of assistance to the clinician in the management of selected patients where the fetus is in danger prior to delivery.

Eclampsia↗

[Concentration of serum globulins, pregnancy globulins, immunoglobulins and estriol in retroplacental blood].

Retroplacental blood samples were received after vaginal deliveries from 22 healthy primi- and multiparae aged between 20 and 30 years. Simultaneously venous blood samples were taken immediately after delivery. Pregnancy specific beta 1-glycoprotein (SP1), pregnancy associated alpha 2-glycoprotein (PZ), immunoglobulins G, M, A, secretory immunoglobulin A (S-IgA), alpha 2-macroglobulin (AMG) and unconjugated estriol were estimated quantitatively in venous as well as in retroplacental blood samples. The concentrations of SP1 in retroplacental blood were significantly lower compared with concentrations in venous blood, whereas estriol concentrations were significantly higher in retroplacental blood. All other factors differed not significantly. Only the IgM concentrations correlated in venous and retroplacental blood samples. The percentages of estimated proteins related to total protein content showed similar proportions in venous as well as in retroplacental blood. The relative protein content of SP1 was significantly lower in retroplacental blood than venous blood samples. The percentage of PZ was significantly higher in retroplacental blood. Among other things these increased concentrations of estriol and PZ in retroplacental blood be able to prevent the rejection of the trophoblast by the maternal endometrium.

Adult↗

Improvement of progressive systemic sclerosis (PSS) with estriol treatment.

Two female patients suffering from progressive systemic sclerosis (PSS) of generalized type were treated with estriol for 10 months. Although complete cure was not achieved, considerable beneficial effects were observed in these patients, but no serious side effects. Thus, skin softening was observed on all involved parts of these patients, which was accompanied by increased mobility of large or medium-sized joints and improved pigmentation and cyanotic redness on fingers and extremities. However, no apparent improvement of internal organ involvement could be detected. Histopathologically, a drastic reduction of homogenization of collagen bundles in the dermis of affected forearms was seen in these patients following estriol treatment. To our knowledge this is the first report of estriol therapy for PSS.

Collagen↗

[Extraction of urinary pregnanediol and estriol by the Bio-Rad column].

In the present study, we have evaluated the quality control parameters of a new method for the determination of the urinary Pregnandiol and Estriol using a small column AG 1X2 proposed by Bio-Rad Laboratories. The principle of this method is based on a single extraction of steroids by ion exchange and methanol elution under different pH conditions. Compared to the "classical" methods using solvent extraction, the present method has some advantages mainly the elimination of the use of large volumes of solvents and the reduction of the sample volume to be analyzed. The preliminary results showed a recovery of 89,0% - 98,9% (C.V. = 5%) for Estriol and 83,8% - 93, 2% C.V = 5%) for Pregnandiol . The precision of the method evaluated by its repeatability and between-assay reproductibility showed 4% and 6% variation for Estriol and Pregnandiol . The Comparison of the present method with a classical one using Ether/Ethanol (4/1) for extraction gave us a very good correlation.

Chromatography, Ion Exchange↗

[Placental morphometric parameters correlated with serum estriol].

In 50 pregnancies morphometric parameters of the placenta and the serum estriol values in the third trimester were correlated. The results show that there is no correlation between the placental parameters as determined by a semi-automatic method and the estriol values in maternal serum in late pregnancy. The placental parameters probably do not reflect the biochemical activity of the trophoblast. A sufficient capacity of the placenta for estriol synthesis must be taken into account independently of its morphological substrate.

Adolescent↗

[Progesterone and unconjugated estriol in amniotic fluid and serum in diabetic patients during induction of labor].

Progesterone and unconjugated estriol are radioimmunologically estimated in 42 diabetic patients in amniotic fluid and serum during last weeks of pregnancy and in the course of oxytocin-induced parturition. As unconjugated estriol rises in progressing weeks of pregnancy progesterone remains unchanged in both investigated fluids. The quotient progesterone unconjugated estriol correlates with affection to labour. There is no statistically significant change in both steroid hormones during induced labour.

Adult↗

Unconjugated estriol in serum as measured by liquid chromatography with electrochemical detection, compared with radioimmunoassay.

Concentrations of unconjugated estriol in maternal serum or plasma increase throughout pregnancy, particularly during the third trimester. We present and discuss the results of a comparative study of unconjugated estriol as measured by a new "high-performance" liquid-chromatographic assay and by a conventional semiautomated radioimmunoassay procedure. In the new method, serum is extracted and chromatographed on a reversed-phase mu Bondapak-C8 column under radial compression. The estriol peak is detected with a glassy-carbon electrochemical detector. The chromatographic results (y) correlated well with the RIA results (x) for 105 samples from 45 pregnant women in their third trimester (y = 1.07x - 0.55 micrograms/L, r = 0.933), with no significant difference between the means of the two methods.

Adult↗

[A study on the relation among oxytocin challenge test, maternal serum estriol level and placental change (author's transl)].

FHR oxytocin challenge test (OCT), maternal serum estriol level, neonatal birth weight and placental findings were studied in 206 cases. 1) Maternal serum estriol levels were not always related to the results of OCTs. 2) In the cases of positive and equivocal OCTs, the birth weight and the placental weight were smaller than those in negative OCT cases. 3) Positive and equivocal OCTs were frequently related with calcification and infarction of the placentae. 4) Neonatal birth weight showed close relation to the placental weight, though insignificant relation to maternal serum estriol level was observed. 5) The frequency of positive and equivocal OCTs was high in the cases of right-posterior position of placenta, and low in the cases of left-anterior.

Adult↗

Radioimmunoassay for salivary estriol, with use of an 125I radioligand and a solid-phase separation technique.

This simple, rapid radioimmunoassay for salivary unconjugated estriol in the third trimester of pregnancy is based on use of a Sepharose-coupled antiserum and a radioiodinated tracer, and requires only a 15-min incubation. Estriol conjugates are shown not to be present in saliva in significant concentrations; therefore a preliminary extraction is unnecessary. Determinations of unconjugated estriol in matched specimens of plasma and saliva correlate well (r = 0.95). A provisional normal range for 30 weeks to term agrees closely with those reported by others. This assay can give results quickly for the large numbers of specimens generated by weekly or daily sampling regimes.

Cross Reactions↗

Total and unconjugated plasma estriol. A comparison.

Total and unconjugated plasma estriol levels from the 24th to the 40th gestational week in 161 normal and 44 pathological pregnancies were studied. A lack of correlation between the two fractions was observed at the different gestational ages, probably due to the different rates of the several metabolic steps which condition the levels of the hormone fractions also in quite physiological conditions. The onset of pregnancy complications further modifies the ratio between the two fractions, as they differently affect the single metabolic processes which are essential for estriol to be produced, conjugated, recovered and excreted. E.P.H. gestosis and poor intrauterine fetal growth can be better diagnosed by the assay of total than unconjugated estriol: the total fraction proved to have the higher sensitivity, predictive value and relative risk and should therefore be preferred for pregnancy monitoring, as it better corresponds to the clinical situation.

Estriol↗