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Estriol antagonism of the action of bradykinin and adrenalin on human umbilical artery.

The effect of estriol on the response of human umbilical artery to bradykinin (0.2 microgram/ml) and adrenalin (0.8 microgram/ml) was studied by an in vitro perfusion method. Estriol (10 microgram/ml) added to the nutrient medium decreased the response of the preparation to the two vasoactive agents. The results suggest the participation of estriol as a modulator of the vascular response at the level of the umbilical circulation, where it may act to protect the maternal-fetal circulatory system from physical or chemical stimuli.

Bradykinin↗

Nuclear binding and retention of the receptor estrogen complex: relation to the agonistic and antagonistic properties of estriol.

The relationship between nuclear retention or residency or receptor estrogen complexes and the agonistic and antagonistic properties of estriol was examined. Cytoplasmic estrogen receptor (Rc) and uterine weight were measured 24 and 48 h after treatment with estradiol (E2), estriol (E3), or or both hormones (E2 and E3). Levels of Rc were elevated in all groups at either time. Since levels of Rc were above control in each case, Rc does not appear to be the limiting factor in the antagonistic effect of estriol. Therefore, the effect of these steroids on translocation and retention of nuclear receptor estrogen complexes (RnE) was examined. Rats were injectd as above and RnE measured by 3[H] estradiol exchange 1, 3, and 6 h after injection. All treatments cause equal translocation of receptor of the nuclear compartment. However, by 6 h the quantity of Rn present in E2 treated animals was significantly above controls while that in E2 + E3 animals was intermediate. E3 alone failed to cause significant nuclear retention of Rn. These patterns of retention correlate with the weight and cytoplasmic receptor responses above and suggest that the short nuclear residency time of RnE3 complexes relates to the antagonism of E3. To test this, these estrogens were administered via paraffin pellets to maintain blood levels of each hormone. Levels of Rn were elevated 24 and 48 h after implant with no significant differences between treatment groups. Likewise, there were no differences in the growth response. Uterine weights were highly stimulated in all three cases (300% above control). These results indicate that E3 acts as an estrogen antagonist when injected as a bolus because of the short nuclear retention time of RnE3 complexes. However, when E3 is present continuously and RnE3 is elevated and maintained, E3 is a potent estrogen without antagonistic properties.

Animals↗

A simple specific assay for estriol in maternal urine.

In medical centers with many high risk pregnancies, the ability to perform a large number of urinary estriol measurements is required. The analytical procedure should provide simplicity, specificity, and economy. A solid phase radioimmunoassay is presented which utilizes antibody generated against an estriol 16-glucuronide-bovine serum albumin conjugate. The assay allows analysis of the principal component of maternal urinary estriol without hydrolysis or purification, with adequate specificity and the capacity for processing large numbers of samples.

Animals↗

Estriol production rates and breast cancer.

We have infused [6,7-3H]estrone or [6,7-3H]estradiol and [4-14C]estriol into seven women who had had breast cancer and into five normal postmenopausal women. We measured the endogenous concentrations and the metabolic clearance rates of estrone, estradiol, and estriol and calculated the blood production rates for these steroids in each group. There were no significant differences between the respective measurements for each group. Our data does not support the argument that physiological amounts of estriol are protective against breast cancer development in women.

Adult↗

Interrelationships among human chorionic gonadotropin (hCG), 17 beta-estradiol, progesterone, and estriol in maternal serum: evidence for an inhibitory effect of the fetal adrenal on secretion of hCG.

In normal pregnancy, maternal serum hCG reaches a maximum concentration about 8-10 weeks after the last menstrual period and then decreases. To investigate the possibility that this decrease in hCG is produced by an inhibitory effect of steroids originating in the feto-placental unit, hCG, progesterone, 17 beta-estradiol, and estriol were determined by specific RIAs in 341 serum specimens obtained from 229 different pregnancies. Expressions for predicted hCG as a function of estimated trophoblastic mass and percent predicted hCG were determined to correct for the increase in hCG with increasing trophoblastic mass. The relationships between hCG and progesterone, 17 beta-estradiol, estriol, or estimated trophoblastic mass were not linear. Expression of the hCG data as percent predicted hCG produced linear relationships between hCG and each of the above steroids. Both hCG itself and percent predicted hCG were shown to have a negative regression on estriol (P less than 0.001) and a positive regression on progesterone (P less than 0.001), but not on 17 beta-estradiol (P greater than 0.05), in a multiple linear regression on all three steroids. These data suggest that hCG production is inhibited by a steroid originating in the fetal adrenal. This inhibitory effect plateaus in late pregnancy, allowing a minor late increase in hCG due to increasing trophoblastic mass.

Adrenal Glands↗

Immunoassay of estradiol: unanticipated suppression by unconjugated estriol.

BACKGROUND: Accurate measurement of estradiol is important in clinical settings. The quality of laboratory estimations of estradiol may be assessed through external quality-assurance surveys. METHODS: Estradiol was measured by microparticle enzyme immunoassay (MEIA) and other immunoassays. Proficiency testing of medical laboratories was conducted using samples prepared from normal male human serum supplemented with exogenous estradiol and other steroid and nonsteroid hormones, and participant laboratories measured estradiol by a variety of commonly used immunoassay techniques. RESULTS: The imprecision (CV) for measurement of estradiol [100-300 ng/L (367-1102 pmol/L)] was </=22% for most analytical techniques. Greater imprecision, as high as 40% for the same concentration range, was observed for the (AxSYM) MEIA method in the proficiency testing event of September 2001. Results from this method were bimodal in distribution. We found that unconjugated estriol at concentrations >1.5 microg/L (>5.2 nmol/L) interfered with the MEIA method, leading to decreased recovery of added estradiol by up to 50%. This suppression in estradiol measurement was prevented by dilution of the specimen before measurement. Addition of unconjugated estriol gave a positive bias in some other immunoassay methods for estradiol. Poor comparability among the immunoassay methods for measurement of estradiol at clinically relevant concentrations [ approximately 60 ng/L (220 pmol/L)] was revealed. CONCLUSIONS: A negative interference of unconjugated estriol with the MEIA method is a source of error for estradiol measurement. Lack of specificity and lack of comparability among immunoassay methods for estradiol may have detrimental effects on medical practice.

Blood Specimen Collection↗

[Composite microassays of plasma progesterone, 17alpha-OH-progesterone, estrone, 17beta-estradiol and estriol in normal adult women. II.Steroid patterns in normal pregnancy, labor and the puerperium (author's transl)].

Plasma progesterone, 17alpha-OH-progesterone, estrone, 17beta-estradiol and estriol in human normal pregnancy, labor and the puerperium were measured simultaneously with radioimmunoassay or competitive protein binding assay. The steroids were extracted from the sample plasma with diethyl either, and were separated through two steps of sephadex LH-20 microcolumn chromatography prior to the assays. From the beginning to the 25th week of pregnancy, a gradual rise in the levels of plasma progesterone was noted, followed by a steep increase toward term with a level of 150-250 ng/ml at the end of gestation. The levels of 17alpha-OH-progesterone during the 7th or 8th week of pregnancy were 2-3 ng/ml, which was above the normal range in the luteal phase, followed by a gradual decrease during 15-25 weeks of gestation. Thereafter, an increase toward term was seen with a mean level of 6-10 ng/ml in the 40th week. From the beginning to the end of pregnancy, plasma levels of estrone, 17beta-estradiol, and estriol increased from less than 0.5 ng/ml to 2-4 ng/ml, from 1-2.5 ng/ml to 6-10 ng/ml, and from less than 1 ng/ml to 6-10 ng/ml, respectively. The disappearance of steroids from maternal peripheral blood in the puerperium was rapid. The half time of progesterone, 17alpha-OH-progesterone, estrone, 17beta-estradiol, and estriol were 72 min, 68 min, 27 min, 27 min, and 48 min, respectively. Analysis of the interrelation between several kinds of steroids of pregnancy, labor, and the puerperium with simultaneous microassays will contribute to the clarification of some important physiological and pathological aspects of feto-placental-maternal functions and steroidogenic functions of the corpus luteum in pregnancy.

Estradiol↗

[Postnatal development of adrenocortical circadian rhythm in neonatally cortisol- and estriol-treated rats (author's transl)].

The effect of a single neonatal administration of cortisol and estriol on the development of the adrenocortical circadian rhythm was investigated in immature rats. In normal control rats of both sexes, the plasma corticosterone rhythm was discernible on day 21. In male rats the adult pattern was observed on day 28, but in females as the plasma corticosterone level elevated progressively during puberty, the rhythm increased in amplitude and the adult pattern was established at 8 weeks of age. In neonatally cortisol-treated rats, the plasma corticosterone rhythm appeared at 4 weeks of age, but the plasma level was significantly lower than that of the controls until 6 weeks and attained a level similar to the controls at 8 weeks. Neonatally estriol-treated rats exhibited the rhythm as early as 2 weeks of age, but this was temporary. It disappeared at 3 weeks and reappeared a 4 weeks. Although 5-week-old males showed normal rhythm as seen in the controls, in females the plasma corticosterone level remained low for weeks and approached the control level at 8 weeks of age. The development of circadian periodicity of adrenal corticosterone content almost paralleled that of plasma corticosterone not only in the controls but also in steroid-treated groups, but the rhythm was occasionally equivocal. In neonatally estriol-treated rats, stress response of plasma and adrenal corticosterone to ether was similar to that of the controls, but the response to exposure to a strange environment was significantly small.

Adrenal Cortex↗

Effects of night work on urinary excretion rates of 6-sulfatoxymelatonin, norepinephrine and estriol in pregnant women.

It has been suggested that shift work, night work in particular, affects worker's psychophysical health. However, the effects of night work on the health of pregnant women are not physiologically well elucidated. The effects of night work on the biological function of pregnant women were studied in the present study. Three pregnant and six non-pregnant nurses that engaged in fast-rotating shift system cooperated for the study. The 24-h urine samples were collected in two time frames, daytime (07:00 to 23:00) and nighttime (23:00 to 07:00) on the day shift, the night shift and the days off. Urinary concentrations of 6-sulfatoxymelatonin and norepinephrine were measured by enzyme-linked immunosorbent assay and estriol by radioimmunoassay. The excretion profiles of urinary 6-sulfatoxymelatonin in the pregnant and the non-pregnant women were altered on the night shift, which might relate the derangement of circadian rhythm of melatonin secretion. The urinary norepinephrine level during the night work was considerably higher in the pregnant women, which indicated the presence of higher physical burden in them due to the night work. The urinary estriol level was not significantly affected by shift, day/night and individual factors, and the effect of night work on urinary estriol level of the pregnant women remained uncertain. The results of the present study suggested that the night work of the pregnant shift workers should be much more relieved.

Adult↗

Endometrial effect of vaginal estriol treatment. A scanning electron microscopic study of the luminal surface.

Estriol, 0.5 mg, was administered intravaginally as ovula once a day for 16 days to 5 menopausal women. Endometrial biopsies were taken before and after the last day of treatment. Before the treatment scanning electron microscopy showed a typical menopausal uterine surface with sparsely occurring ciliated cells among the non-ciliated ones. The non-ciliated cells possessed a small number of short microvilli. After estriol treatment the ciliated cells occurred more frequently. The cells possessed more numerous and longer microvilli and several non-ciliated cells showed apical protrusions. These changes are considered to be signs of an estrogenic influence. It is concluded that the estriol release from the vaginal ovula is sufficient to induce an estrogenic response in the surface of the uterine epithelium.

Aged↗

Concentration of unconjugated estriol in capillary whole blood from pregnant women.

A radio-immunological method applied to the estimation of unconjugated estriol in capillary whole blood is described. The concentration of unconjugated estriol in capillary whole blood and venous serum from 35 pregnant women was measured. Close relation was found between values in venous serum and capillary whole blood. The intra-assay variation was 4.9% for venous and 7.8% for capillary whole blood samples when analysed in duplicate. The day-to-day variability was of the same order for venous (10.0%) as for capillary (8.4%) samples. It is concluded that unconjugated estriol can be measured in small amounts (25 microliter) of capillary whole blood and that this method offers practical advantages over methods using venous serum or plasma.

Capillaries↗

Ethinylestradiol and desogestrel, alone or in combination with two doses of estriol. Effects on plasma proteins.

Nineteen fertile women were treated with three differently composed oral contraceptives in a cross-over study and were randomly allocated to begin with one of the three preparations. The tablets contained 0.030 mg ethinylestradiol +0.15 mg desogestrel alone (A) or in combination with either 0.5 mg estriol (B) or 2 mg estriol (C). After two treatment cycles on each preparation, blood samples were obtained and analysed for ceruloplasmin, SHBG, prealbumin, transcortin and thyroxine-binding globulin. No differences were found in the induction of liver protein synthesis. It was concluded that the addition of estriol in doses of 0.5 or 2 mg did not influence the effects induced by ethinylestradiol.

Adolescent↗

Effects of inorganic salts on solubilization of estriol in an aqueous solution of poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer.

The effects of inorganic salts on the solubilization of estriol was studied in an aqueous solution of a poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer (Pluronic L-64). The solubility of estriol increased with increasing Pluronic L-64 and salt concentrations. Furthermore, two clear transition points corresponding to the polymolecular micelle formation and a pronounced change in micellar structure of Pluronic L-64 were found on the solubility curves. The effectiveness of inorganic salts for increasing solubility of estriol followed approximately the lyotropic or Hofmeister series, except Li+.

Drug Compounding↗

Effect of oral estriol on urogenital symptoms, vaginal cytology, and plasma hormone level in postmenopausal women.

OBJECTIVE: To evaluate the effects of oral estriol on urogenital symptoms, vaginal cytology, and plasma follicle stimulating hormone (FSH) and estradiol level in postmenopausal women with urogenital symptoms. METHOD: Twenty-eight postmenopausal women with urogenital symptoms who volunteered to participate in this study received 2 mg of oral estriol daily for 12 weeks. The urogenital symptoms, vaginal cytology, and plasma hormone level before and after treatment were analysed using paired t-test. RESULTS: The genital and urological symptoms improved (P < 0.05) after treatment in all subjects. The vaginal cytology showed estrogenic effect on the karyopyknotic index and maturation value. There was a significantly (P < 0.05) higher level of plasma estradiol after 12 weeks of treatment. However, the difference of plasma FSH level before and after treatment was not statistically significant. CONCLUSION: The daily oral estriol had a positive effect on the urogenital symptoms and vaginal cytology. The plasma estradiol increased after 12 weeks of treatment but the plasma FSH did not change.

Administration, Oral↗

[The rapid determination of urinary estriol in pregnancy by thin layer chromatography (author's transl)].

A simplified method for the determination of urinary estriol in pregnancy by thin layer chromatography is described. After precipitation of the conjugated substances with ammonium sulfate a short hydrolysis is carried out. Estriol is extracted with diethylether and coupled with dark blue R salt to an azo-dye. After thin layer chromatographic isolation, a spectrophotometric determination from the chromatogram is done. The recovery rate is 94%. The mean error in serial determination is +/- 5,4%. 1 nanogram (10(-9) g) of estriol can be determined from the thin layer chromatogram. The time required to obtain a result is just over 1 hour.

Chromatography, Thin Layer↗

[Specific determination of estriol-16-glucuronide from the urine of pregnant women in the last trimester].

A method for quantitative estimation of estriol-16-glucuronide in urine of pregnant women is given. The glucuronide is isolated by precipitation with ammoniumsulfate (70% w/v) followed by extraction with ether-ethanol (3:1). The estriol-16-glucuronide is converted with dark blue r to an azodye, which is separated from colored impurities by passing through a small column of sodium sulfate. The absorbance of the eluted dye is measured at 520 nm. 75 cases were analyzed and it was found that the estriol-16-glucuronide excretion increases in the 3rd trimester of pregnancy from the average value of 9.06 mg/24 hours in the 28th week to 22.11 mg/24 hours in the 42nd week of pregnancy.

Adult↗

[Excretion of estriol in pregnancy complicated by diabetes].

A study was made of estriol excretion in the urine of women during normal pregnancy and in pregnancy against the background of diabetes. It was revealed that estriol secretion was decreased in pregnant women suffering from diabetes. As supposed there existed an interrelationship between the diabetic status and the level of estriol excretion.

Blood Glucose↗