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PubMed2001

Estriol improves membrane fluidity of erythrocytes by the nitric oxide-dependent mechanism: an electron paramagnetic resonance study.

The present in vitro study was performed to investigate the effects of estriol (E3) on membrane fluidity of erythrocytes by means of an electron paramagnetic resonance (EPR) and spin-labeling method. E3 was shown to significantly decrease the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS obtained from EPR spectra of erythrocyte membranes. This finding indicated that E3 might increase the membrane fluidity of erythrocytes. The effect of E3 was significantly potentiated by the nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP), and a cyclic guanosine 3',5'-monophosphate (cGMP) analog, 8-bromo-cGMP. In contrast, the change in the membrane fluidity induced by E3 was antagonized by the NO synthase inhibitor, L-NG-nitroarginine-methyl-ester (L-NAME), and asymmetric dimethyl-L-arginine (ADMA). The results of the present study showed that E3 significantly increased the membrane fluidity and improved the microviscosity of erythrocyte membranes, partially mediated by an NO- and cGMP-dependent pathway. Furthermore, the data might be consistent with the hypothesis that E3 could have a beneficial effect on the rheological behavior of erythrocytes and may play a crucial role in the regulation of microcirculation.

Arginine↗
PubMed1975

[Composite microassays of plasma progesterone, 17alpha-OH-progestrerone, estrone, 17beta-estradiol and estriol in normal adult women. I. Assay methods and steroid patterns in normal menstrual cycle (author's transl)].

Composite microassays for plasma progesterone (P), 17alpha-OH-progesterone (17P), estrone (E1), 17beta-estradiol (E2), and estriol (E3) were developed. Steroids were extracted from plasma samples with diethyl ether, and were separated from each other through two steps of sephadex LH-20 microcolumn chromatography (benzene:methanol 85:15, and n-hexane: benzene: methanol 80:10:10), prior to assays by radioimmunoassay (P, E1, E1, and E3) and competitive protein binding assay (17P). Steroids were recovered satisfactorily through these procedures (mean recovery; P:107.6%, 17P:102.3%, E1:88.2%, E2:84.1%. E3:78.5%). The detectable range for P, 17P, E1, E2, and E3 were 0.01-2 ng/tube, 0.1-10 ng/tube, 10-2000pg/tube, 10-2000 pg/tube, and 0.5-100 ng/tube. The interassay coefficient of variations were less than 10.7%, 15.2%, 17.8%, 11.4%, and 28.1%, respectively. These steroids were measured daily in 4 menstrual cycles from 4 normally menstruating women. Plasma FSH and LH were quantitated previously. The following results were obtained; 1) Plasma P elevated from around LH surge (Day O), and reached a peak on day +5 approximately +7 with the values of 12.74 +/- 2.34 ng/ml (Mean +/- S.D.). 2) Slight decrease in P levels was noted on day +8 approximately +9. 3) A peak in 17P was observed in the preovulatory phase (day -3 approximately -1) with the values of 0.6 approximately 1.3 ng/ml in three of four cases. 4) Changes of 17P during the luteal phase were paralleled to those of P with a peak of 1.16 +/- 0.31 ng/ml on day +5 approximately +7. 5) No remarkable patterns were found in E1 levels throughout the menstrual cycle. 6) A sharp peak in E2 was detected in the preovulatory phase (day -1 approximately 0) with the values of 709.2 +/- 95.9 pg/ml. 7) The second peak of E2 with 378.6 +/- 140.7 pg/ml was observed in the late luteal phase (day +8 approximately +12). 8)E3 was not detected in all samples. The interrelationship between steroids and the correlation with the morphological changes of the ovaries in the normal menstrual cycle are discussed. In the follicular phase, the theca interna cells around the maturing follicle may be growing under the influence of pitiutary gonadotropins to secrete large amounts of 17P and E2, which may possibly affect the pituitary for LH surge, followed by ovulation. In the luteal phase, both the granulosa cells and theca intera cells are luteinized, which may produce and secrete large amount of P, 17P, and E2.

Estradiol↗
PubMed1981

[The concentration of serum unconjugated estradiol, estriol and estetrol in pregnant women, and the significance of these hormones in pregnancy (author's transl)].

Simultaneous determinations of unconjugated estradiol (E2), estriol (E3) and 15 alpha-hydroxyestriol (E4) levels in maternal serum were studied serially to ascertain the significance of these estrogens in the feto-placental unit. The samples of serum were collected serially from 25 normal and 44 abnormal pregnancies. In normal pregnancy, these estrogen levels increased throughout pregnancy, especially E3 and E4 nearing the term. In 15 cases of IUGR pregnancy (including 4 cases of perinatal death), E2 levels were mostly low (less than M -- S.D.), E3 was within normal limits (M +/- S.D.) or low, and E4 was either high (greater than M + S.D.) or relatively low, and normal. In 9 cases of twin pregnancy, most E2 levels were within normal limits, while E3 and E4 were remarkedly high. The results signified that E2 indicated placental function, that E3 indicated placental and fetal function, and that E4 indicated fetal function.

Estetrol↗
PubMed1982

[Dynamics of estriol-16-glucosiduronate (E3-16-G) in early pregnancy -- its prognostic value in complicated pregnancy (author's transl)].

Urinary estriol-16-glucosiduronate (E3-16-G) in early pregnancy was measured by a direct radioimmunoassay which was highly specific for the compound and did not require hydrolysis or chromatography. The level of E3-16-G in normal pregnant women increased as pregnancy progressed and was over the level in non-pregnant women after 6 weeks gestation. The levels were lower in complicated pregnancies, namely threatened abortion, intra uterine fetal death, ectopic pregnancy, anencephalus and so on. Decreases of urinary E3-16-G in threatened abortion were more rapid than those of urinary hCG, which was used as a useful prognostic indicator in those cases. These results suggested the possibility that the fetus played some role in the production of E3-16-G in early pregnancy. In order to clarify the role of the fetus in the formation of E3-16-G, it was measured in the maternal peripheral vein, uterine artery and vein, and in the fetal tissue at hysterectomy in complicated pregnancies (three cases). These results also suggested the possibility that E3-16-G was produced by the fetus. In the in vitro experiments where 14C-E3 was incubated with various tissues in early pregnancy, it was demonstrated that 14C-E3 was conjugated to be E3-16-G by homogenate of the fetal tissue in 8 weeks gestation, and by the liver and by the kidney in 13 weeks gestation but not by chorionic tissue. These results indicated that the conjugation process of E3, though perhaps not entirely, proceeds in the fetus and the urinary determination of E3-16-G might give us good information about the fetus in pregnant women.

Abortion, Threatened↗
PubMed1984

Simultaneous and serial measurement of serum levels of human placental lactogen, beta-human chorionic gonadotropin and unconjugated estriol levels in pregnant women.

Serum levels of human placental lactogen (hPL), beta-human chorionic gonadotropin (beta-hCG) and unconjugated estriol (E3) were measured simultaneously and serially in regular menstrual late pregnant women (155 samples) by radioimmunoassay. The peak of beta-hCG level was shown at 37 weeks' gestation. After that, there was a moderate decline of the beta-hCG level. Serum hPL showed the peak at 30 weeks' gestation. The level of unconjugated E3 rose toward 41 weeks' gestation. In the 155 samples, there were significant positive correlations among these hormone levels. Also, there were highly significant positive correlations between placental weight and these three hormone levels. Only unconjugated E3 level which was obtained within a week before the onset of labor had a significant positive correlation with birth weight. These data suggest that even in late pregnancy, maternal beta-hCG makes a peak and may change parallel with hPL and unconjugated E3. Only the unconjugated E3 level may be affected by fetal growth.

Birth Weight↗
PubMed1989

Different responses of albumin-containing and alpha-fetoprotein-containing cells to estriol in the adult mouse liver.

A single intraperitoneal injection of 10 mg estriol (E3) rapidly induced a transient decrease in the serum albumin (ALB) level in 3 to 5 days in adult mice. At a dose of 5 mg, E3 showed a remarkable threshold effect on the decline of serum ALB. By immunohistochemistry, two types of ALB-positive cells were found in the liver. Type 1 cells were stained intensely and almost homogeneously throughout all or nearly all their entire cytoplasm, and type 2 cells showed only granular or vesicular cytoplasmic deposits. After administration of 10 mg E3, the type 1 cells diminished rapidly and markedly in direct proportion to the fall in serum ALB from the centro- and mediolobular zones, where they had been normally localized either singly or in small groups. Simultaneously, the granular or vesicular deposits that had been normally stained very weakly in the type 2 cells in the centro- and mediolobular zones became intensely stained along with cells in the perilobular zone. Alpha-fetoprotein (AFP)-containing cells in the liver appeared in maximal numbers at 5 to 7 days after E3 administration. These serological and cytological changes after E3 administration are here discussed on the basis of a possible inverse relationship between ALB and AFP gene expression.

Albumins↗
PubMed1995

Promotion by estriol of the development of grafted fetal livers in mice.

Mouse fetal livers of 12 days gestation were transplanted beneath the kidney capsule of syngeneic castrated male hosts. Recipients received a single intraperitoneal injection of 5 mg estriol (E3) immediately after transplantation and were sacrificed 4, 7 and 14 days later. Control mice received injections of solvent only. The fetal liver grafts of the E3 groups showed remarkable growth compared with the control grafts at each corresponding time. In the grafted fetal livers of the E3 groups, many more basophilic hepatocytes appeared for much longer periods, and the early formation of wide sinusoids was noted. Although hemopoietic activity had almost ceased a short time after transplantation in the control grafts, many prominent extrasinusoidal erythroid, granulocytic and megakaryocytic hemopoietic foci developed and persisted to the end of the experiments in the grafted fetal livers of the E3 groups. In the next experiment, the recipients received three injections of 0.5-5 mg E3 at 5-day intervals, and were sacrificed 21 days after transplantation. Control animals received solvent only in the same manner. The fetal liver grafts of the E3 groups also showed remarkable, dose dependent growth. The growth was particularly striking at doses of 3-5 mg E3. In the grafts of these groups, basophilic hepatocytes were predominant, and hepatic cords and sinusoids were well formed. Moreover, sinusoidal erythropoiesis was intense. These results provide evidence for the possible role of E3, secreted from the placenta into the fetal circulation, in the development of the fetal liver.

Animals↗
PubMed1979

Estradiol, estriol and human placental lactogen in serum in threatened abortion.

In 64 pregnant women admitted to hospital because of threatened abortion the prognostic value of estradiol-17-beta, estriol and human placental lactogen (HPL) in serum was examined. The hormones were determined by radioimmunoassay. Blood samples were taken at regular intervals during admission to hospital and subsequently until delivery. For each hormone a reference range was based on the hormone values obtained from the pregnancies that continued to viability. The study shows that the three hormones examined gave a good indication of the prognosis in threatened abortion, both separately and in combination. The best predictive values were achieved with estradiol and HPL after serial samples. Of these two hormones estradiol is to be preferred because of its fetoplacental origin.

Abortion, Threatened↗
PubMed1983

Serum estriol level during treatment with betamethasone in the last trimester of human pregnancy.

A comparison was made between betamethasone disodiumphosphate/betamethasone acetate (Celeston) and betamethasone disodiumphosphate (Celestona) in antenatally prophylactic treatment of respiratory distress syndrome syndrome (RDS). Altogether 65 pregnant women in the last trimester of pregnancy were treated with the first-mentioned drug and 62 with the second. The RDS-preventive effect was the same in the two groups. Celeston has a much longer depressive effect on the level of plasma estriol than has Celestona. Use of this drug, betamethasone disodiumphosphate, is therefore recommended in the prophylaxis against RDS.

Betamethasone↗
PubMed1983

Plasma estriol in late pregnancy in relation to fetal outcome.

The study is a retrospective report on the capacity of plasma (P-) estriol (E3) determinations in late pregnancy to detect abnormal fetoplacental state at delivery. From the material of cases with P-E3-determinations, two extreme groups were chosen for comparison: those with absolutely normal fetoplacental status at parturition and those with severe disturbances of the fetoplacental status at delivery. The predictability of a single P-E3 value was generally low, especially at the end of pregnancy. Consecutive (at least 3) high or low values, respectively, in the individual case, proved to have a predictable value that might complement other clinical methods for assessing fetoplacental function.

Apgar Score↗
PubMed1984

The predictive value of total estriol; HPL and Hb on perinatal outcome in severe pre-eclampsia.

The prognostic value of total maternal plasma estriol, human placental lactogen (HPL) and hemoglobin (Hb) with regard to perinatal outcome was compared in 74 cases of severe pre-eclampsia. No combination of the tests predicted all cases of fetal and newborn pathology. HPL was the most reliable single test in cases of intra-uterine growth retardation, while Hb was the best predictor of severe fetal pathology and perinatal distress. In cases of severe fetal and neonatal pathology, the prognostic value of the combination of HPL and Hb was more reliable than the combination of all the three tests.

Adult↗
PubMed2000

The prediction of adverse pregnancy outcome using low unconjugated estriol in the second trimester of pregnancy without risk of Down's syndrome.

To investigate the relationship between low unconjugated estriol (uE3) levels in the second trimester and adverse perinatal outcomes in pregnancies without increased risk for Down's syndrome, 1,096 women under 35 years of age underwent a mid-trimester AFP-hCG-uE3 screening test between January 1995 and June 1998. Multiple pregnancies, maternal diabetes, smoking and elevation of AFP and hCG levels more than 2.0 multiple of median (MoM) were excluded from our study population. The results were divided into a low-uE3 group with uE3 levels at or below 0.75 MoM and a normal uE3 group with uE3 levels above 0.75 MoM. The risk for adverse pregnancy outcome was compared between the two groups and the role of low uE3 as a predictor of adverse pregnancy outcome was determined. The data were assessed using chi 2 or Fisher exact test and then logistic regression was used for the final analysis. The odds ratio (OR) and corresponding 95% confidence intervals (CI) were also calculated. Unconjugated E3 levels at or below 0.75 MoM was significantly associated with fetal growth restriction after adjustment for maternal age, weight, sampling weeks, AFP and hCG levels (OR 0.413, 95% CI 0.174-0.900; P = 0.035). Low uE3 levels in the second-trimester could help in the detection of fetal growth restriction by a low risk group in Down's syndrome. Careful gestational dating and serial clinical and sonographic assessment of fetal growth may be required for the clinician to manage these parturients.

Adult↗
PubMed2000

Comparison of usefulness of estradiol vaginal tablets and estriol vagitories for treatment of vaginal atrophy.

BACKGROUND: Atrophic vaginitis is a common condition. This study compared the usefulness of estradiol vaginal tablets (EVT) and estriol vagitories (EV) in treatment of atrophic vaginitis. METHODS: Ninety-six postmenopausal women with symptoms of atrophic vaginitis were treated for 24 weeks with either EVT or with EV. Patients used the medication daily for the first 2 weeks of the study, and twice-weekly thereafter. RESULTS: Both EVT and EV were effective in treating vaginal atrophy and patients in both treatment groups experienced a significant improvement in vaginal symptoms such as itching, irritation, dryness, and dyspareunia. At the end of the study three (6%) EVT treated women reported leakage and none needed to use sanitary towels. Among the EV treated women 31 (65%) reported leakage and 14 (29%) required sanitary protection. Furthermore, 90% in the EVT group perceived the medication as hygienic compared to 79% in the EV group, and 49% in the EVT group indicated that the product was easy to use compared to 28% in the EV group. Endometrial thickness was increased (1.1 mm with EVT and 0.5 mm on EV) in both treatment groups during the first 2 weeks of the study, but returned to baseline levels when the frequency of drug application was reduced to twice-weekly. CONCLUSIONS: Estradiol vaginal tablets provides an effective alternative to traditional forms of local estrogen therapy.

Administration, Intravaginal↗
PubMedDate not supplied

[Correlated interrelationships between the concentrations of chorionic gonadotropin, progesterone and estriol in normal pregnancy].

A study was made of 151 healthy pregnant women at periods of from 4 to 41 weeks of pregnancy. There was revealed no correlation between the level of excretion of the CG and estriol, and also of the CG and pregnandiol from the 7th to the 41st weeks of pregnancy; consequently CG played no role in the regulation of steroidogenesis in the placenta. Between the levels of CH and progesterone in the blood there existed a significant positive association from the 4th to the 7th week of pregnancy; this correlation disappeared from the 8th week. Consequently, the CG retained its steroidogenic action on the corpus luteum of pregnancy. The activity of the corpus luteum in respect to progesterone production decreased considerably as soon as the 7th week of pregnancy.

Chorionic Gonadotropin↗
PubMed1975

A simple radioimmunoassay for unconjugated estriol in pregnancy plasma.

A simple and specific radioimmunoassay (RIA) for the measurement of plasma or serum unconjugated estriol (E3) in pregnancy is described for general laboratory use. Two different antibodies utilized had low cross-reaction to estrone (E1) and estradiol-17 beta (E2). With either of these antibody reagents, a method was designed that requires only an extraction step using a specific solvent mixture of ethyl acetate and n-hexane (3:2, v/v), one-hour incubation with working antibody, and separation of bound from free E3 by ammonium sulfate. Standard curves useful in the range of 0 to 2,000 pg. were obtained. This assay, requiring only 0.05 ml. of plasma, can be completed within 4 hours. The sensitivity of this RIA was 10 pg. The intra- and interassay coefficients of variation (CV) were 5.0 and 9.4 per cent, respectively. When E3 determinations by this method are compared with RIA values by a more complicated technique using Celite column chromatography, the results are not significantly different. There was a good correlation between our RIA and a standard urine E3 determination (n = 137, r = 0.82, p less than 0.001). Using our simplified method, the mean plasma E3 during pregnancy were 1.0 +/- 0.6 ng. per milliliter at 10 weeks, 2.3 +/- 0.6 ng. per milliliter at 20 weeks, 6.5 +/- 1.4 ng. per milliliter at 30 weeks, and 16.5 +/- 5.1 ng. per milliliter at term. Since the serum RIA reflects changes in free E3 which has a shorter half-life than conjugated E3, this rapid and simple method is attractive as an approach to monitor fetal-placental function.

Estriol↗
PubMed2003

Method comparison studies for prostate specific antigen and unconjugated estriol immunoassays.

OBJECTIVE: Method comparison studies were performed in order to move a semi-automated prostate specific antigen (PSA) immunoassay and a manual unconjugated estriol (uE3) immunoassay to an automated chemistry immunoassay analyzer. The results of the two method comparison studies are compared. DESIGN: Serum samples collected on patients with physician orders for PSA or uE3 were assayed by both methods. PSA samples were assayed on a Hybritech Tandem Photon ERA and on two Beckman Coulter Access instruments. UE3 samples were assayed by RIA and on two Beckman Coulter Access instruments. Linear regression analysis was performed on both sets of data and within-run precision and dilution studies were performed on the PSA Access method. SETTING: Clinical chemistry laboratory, West Virginia University Hospitals Inc, Morgantown WV. RESULTS: PSA linear regression analysis for the two methods (ERA and Access 1) were y = 1.0008x + 0.0393, r = 0.9976, SE = 0.1319, n = 37 and (ERA and Access 2), y = 1.0019x + 0.0486, r = 0.9964, SE = 0.1632, n = 37. Within-run precision studies for both Access instruments produced acceptable coefficient variations and dilution study results were in PSA reportable range. uE3 linear regression analysis for the two methods (RIA and Access 1) were y = 1.4105x - 0.3741, r = 0.8696, SE = 0.8330, n = 33 and (RIA and Access 2) were y = 1.315x - 0.2292, r = 0.8643, SE = 0.7964, n = 33. CONCLUSION: The results of the method comparison studies for PSA were acceptable and the automated PSA immunoassay method was adopted. The results of the uE3 comparison studies did not show good correlation; the automated method was not adopted.

Automation↗
PubMed1992

Maternal serum screening for fetal Down syndrome in women less than 35 years of age using alpha-fetoprotein, hCG, and unconjugated estriol: a prospective 2-year study.

OBJECTIVE: To evaluate prospectively maternal serum screening with alpha-fetoprotein (AFP), hCG, and unconjugated estriol (uE3) as a screen for fetal Down syndrome. METHODS: Women less than 35 years of age were offered screening between 15-20 weeks' gestation. Screening results calculated by an algorithm to be equal to or greater than 1:274 (the risk of a 35-year-old for fetal Down syndrome at the second trimester) were considered positive. If gestational age was confirmed by ultrasonography, genetic counseling and amniocentesis were offered. RESULTS: In the first 2 years of our program, 9530 women were screened, of which 686 (7.2%) were found to be screen-positive. Ultrasonographic examination explained the abnormal values in 379 (4.0%). The remaining 307 (3.2%) received genetic counseling and 214 (2.2%) elected amniocentesis or CVS. Four cases of fetal Down syndrome and one de novo chromosomal marker were detected. In three additional cases of fetal Down syndrome, triple-analyte screening failed to identify the pregnancies to be at increased risk. None of the seven cases of fetal Down syndrome would have been detected through screening with maternal serum alpha-fetoprotein (MSAFP) and age alone. CONCLUSIONS: Measurement of MSAFP, hCG, and uE3 in women less than 35 years old is an effective screening test for fetal Down syndrome, with a sensitivity of 57% in our study and an amniocentesis rate (false-positive rate) of 3.2%.

Adult↗