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Quantitative measurement of 17 beta-estradiol and estriol in river water by time-resolved fluoroimmunoassay.

A sensitive method for detecting 17 beta-estradiol (E2) and estriol (E3) in river water has been developed, based on the time-resolved fluoroimmunoassay by using a fluorescent europium chelate label, 4,4'-bis(1",1",1",2",2",3",3"-heptafluoro-4",6"-hexanedion-6"-yl)- chlorosulfo-o-terphenyl (BHHCT)-Eu3+. In the E2 assay, microtiter plates were coated with the E2-bovine serum albumin (BSA) conjugate. The anti-17 beta-estradiol antibody, the biotinylated goat anti-rabbit IgG antibody and the BHHCT-Eu3+ labeled streptavidin (SA)-BSA conjugate were used. In the E3 assay, the goat anti-rabbit IgG antibody was coated on a microtiter plate. The anti-estriol antibody and the BHHCT-Eu3+ labeled E3-BSA conjugate were used. The detection limits for E2 and E3 were 2.3 pg/ml and 4.3 pg/ml, respectively, and the analytical recoveries were 95-120%. Quantitative measurement of estrogens in river water was carried out for Kanda River (Tokyo, Japan) by using the method. The E2 and E3 levels were 32 pg/ml and 5.5 pg/ml, respectively. The detection limits of the present method are in the same orders of magnitude as those of ELISA for E2, and are 1-2 orders of magnitude better for E3.

Animals↗

The induction of epidermal ornithine decarboxylase following UV-B irradiation is inhibited by estriol.

The induction of epidermal ornithine decarboxylase (ODC) can be partially blocked by corticosteroids, retinoic acid or active vitamin D3. The influence of the other members of this so-called "steroid hormone receptor superfamily", namely the sex-steroids and thyroid hormone, is unknown in epidermis, but they enhance ODC induction in certain other tissues. Here we investigated whether topical estriol leads to a spontaneous and/or enhanced epidermal ODC induction 8 h after UV-B irradiation of 6 postmenopausal women. Contrary to expectation, estriol did not stimulate induction but reduced induction by 44%. This observation raises the possibility that all members of the steroid hormone receptor superfamily may share a common AP-1 binding site.

Administration, Cutaneous↗

Effects of betamethasone on plasma levels of estriol, cortisol and HCS in late pregnancy.

The effect of a single dose of betamethasone on the maternal plasma concentration of estriol and cortisol was studied. The concentration of estriol decreased rapidly. A maximal suppression of about 70 per cent was seen after 6-24 hours. A similar influence on the maternal plasma concentration of cortisol was observed. HCS (human chorionic somatomammotropin) was not influenced by betamethasone. These facts have to be taken into consideration after treatment with synthetic corticosteroids in high risk pregnancies.

Adult↗

Plasma estriol, progesterone, cortisol, placental lactogen and alpha-fetoprotein in a pregnancy with an anencephalic fetus followed from the seventh week till term.

Concentrations of total estriol, progesterone, cortisol, human placental lactogen and alpha-fetoprotein were measured in maternal venous plasma at regular intervals from the seventh week of pregnancy until term in a woman with an anencephalic fetus. Except for the first trimester, during which the values were in the lower normal range, the concentration of estriol was constantly subnormal. The "physiological" rise in cortisol levels was absent. Progesterone and HPL were both within the low normal range. The levels of alpha-fetoprotein were transiently raised during the 13th--25th weeks of pregnancy.

Adult↗

Plasma progesterone, serum estriol and plasma HPL determinations during the last trimester to detect changes before spontaneous labor. Comparison of progesterone assay using RIA and CPB.

Conflicting results have been published regarding changes in plasma progesterone during the last trimester of pregnancy. Some have demonstrated a fall in plasma progesterone before labor, and this has been taken as a possible explanation of the onset of labor. It has been suggested that the various results could be due to differences in methods for progesterone determination. In this study the progesterone levels were determined by both RIA and CPB. In 11 women the plasma progesterone, human placenta lactogen, and serum estriol were measured weekly during the last trimester of normal pregnancies and immediately after delivery. All samples were analysed radioimmunologically. In order to compare the radioimmunoassay and competitive protein binding techniques (RIA and CPB), the progesterone levels were determined by both methods. This was also done for 80 successive plasma progesterone routine samples drawn from women who were not pregnant or who were in the early stages of pregnancy. Both methods showed a significant rise in the plasma progesterone level during the last 6 weeks before spontaneous labor. However, the values obtained were lower when assayed by CPB than by RIA, presumably because of a higher specificity and a cross reaction in RIA. Serum estriol exhibited increasing values throughout pregnancy, but without a significant rise during the last few weeks. Plasma HPL settled at a constant level during the last few weeks before labor.

Estriol↗

A clinical evaluation of treatment with estriol vaginal cream versus suppository in postmenopausal women.

Thirty postmenopausal women with vaginal atrophy were treated with a vaginal cream or vaginal suppositories containing 0.5 mg estriol (OvestinR, Organon, The Netherlands). The preparations were given daily for 14 days and then during the next 6 weeks a maintenance dose was applied twice a week. Cervical mucus, vaginal cytology and the endometrium were studied. Blood samples were analysed for unconjugated and conjugated estriol, FSH, LH, prolactin and sex hormone binding globulin capacity, before and after 2 weeks of treatment. Subjective relief of vaginal symptoms was reported by all patients. Restoration of vaginal mucosa was confirmed by colposcopy. Some women noted a feeling of transient "vaginal heat" during the first days of treatment; otherwise no side effects were reported. Higher values for Spinnbarkeit, ferning and karyopyknotic index were found for the cream group on day 14. No endometrial stimulation was detected as judged by light microscopy in any of the samples. No significant differences between the preparations were found for any of the hormone variables, or sex hormone binding globulin capacity, except for prolactin levels after 2 weeks of treatment. Possible reasons for the disparity between the two preparations regarding peripheral variables are discussed.

Aged↗

Serum estriol level during treatment with pivmecillinam.

Asymptomatic bacteriuria in pregnant women shall always be treated, because of the risk of development of acute pyelonephritis. Some antibiotics reduce the level of serum estriol and therefore are less suitable in the treatment of cystitis in the last trimester of pregnancy. Mecillinam is found effective against the most frequent urinary pathogen in cystitis in pregnancy (escherichia coli), and as it is found not to reduce the level of serum estriol it is concluded that pivmecillinam/mecillinam is an alternative in the treatment of symptomatic and asymptomatic urinary tract infections in the last trimester of pregnancy.

Amdinocillin Pivoxil↗

Antiprostatic effects of a nitrogen mustard of estriol.

The chemical ester of a nitrogen mustard with estriol was tested for its antiprostatic effects in dogs and rats. The E33-mustard was shown to interfere with the uptake of labeled estriol in the dog prostate and by the ventral prostate of the rat; and to increase the uptake of the radioactivity associated with testosterone in the dog prostate. The weights of the ventral and dorsolateral prostates of the rat were significantly reduced following the administration of E3-mustard for 2 days. The results are interpreted to be very similar to those obtained with the mustard of E (Estracyt) and the effects are probably a combination of the actions of the released estrogen (D) and/or mustard, either adding individually or in concert.

Animals↗

The effect of combined iron therapy (Chemiron) and single iron therapy on the dexamethasone-estriol reaction test for placenta insufficiency during normal pregnancy.

Impaired uteroplacental perfusion has been shown to play a role in the pathogenesis of some complicated pregnancies with placenta insufficiency. Apart from this, lower oestrogen, magnesium and zinc are found in many of these conditions in the third trimester with placenta insufficiency. In this study, we examined the effect of a 4 mg intravenous dexamethasone injection on estriol, since maternal cortisol or synthetic corticosteroids cross the placental barrier and inhibit the release of dehydroepiandrostesone sulfate in the fetal adrenals. Dexamathasone was found to suppress estriol levels in all groups but a significant difference in suppression was found between the Chemiron--a new combination hematinic--and the control single iron therapy groups. Our preliminary results showed that Chemiron has a protective effect on the development of placenta insufficiency during the third trimester of pregnancy.

Adult↗

[Effect of estriol treatment per vaginam before Burch culposuspension].

BACKGROUND: To assess the effect of estriol treatment per vaginam before Burch culposuspension in postmenopausal women with stress urinary incontinence (IUS). METHODS DESIGN: prospective randomised study. SETTING: Department of Gynaecology, Obstetrics and Physiopathology of Human Reproduction-Medical School-University of Naples Federico II . PATIENTS: twenty women in postmenopause at least from five years with a urogenital symptomatology due to IUS. INTERVENTIONS: women were randomised into one of two groups (treated or control) and they were submitted to an evaluation of vulva and vagina trophism. All the women were submitted to a urodynamic examination and to a transvaginal ultrasonography with evaluation of pubis-bladder neck distance, bladder and proximal urethra position, before treatment, one week before the operation and after six months from the same operation. EVALUATIONS: subjective symptomatology and urodynamic parameters between treated and control groups before and after operation. RESULTS: After 12 weeks of treatment, a significant improvement of subjective symptomatology and a not significant improvement of all the urodynamic parameters in the treated group in comparison with the control group have been demonstrated, while any anatomic alteration compared with the basal hasn t been observed. After six months from the operation in all the women a significant reduction of subjective quantity of urine lost after a strain has been demonstrated and significant variations of urodynamic parameters without significant differences between treated group and control group were also observed. CONCLUSIONS: The estriol treatment per vaginam is not so effective on the result of Burch culposuspension in postmenopausal women with IUS.

Administration, Intravaginal↗

Estradiol- and estriol-binding in human benign prostatic hyperplasia.

Binding of the natural estrogens, estradiol and estriol, was investigated, in 34 samples of human benign prostatic hypertrophy (BPH) tissue, using Scatchard analysis and agar gel electrophoresis. Saturation binding analysis using a wide range of concentrations of both ligands resulted in curvilinear Scatchard plots. This confirmed the presence of two binding forms for estradiol: a true estrogen receptor, and a protein with lower affinity and higher capacity. Both binding species were also demonstrated and quantified with estriol. The electrophoretic process, after incubation at low and high ligand concentrations also resulted in separation, for both estrogens, of two binding peaks. They are probably two distinct forms of the low affinity, high capacity binding measured by Scatchard. The procedure used in our laboratory was not able to provide accurate determination of the concentrations of these binding forms. Possible modifications to alleviate these drawbacks are discussed.

Electrophoresis, Agar Gel↗

[Radioimmunological determination of unconjugated plasma estradiol and estriol after administration of dehydroepiandrosterone sulfate in late pregnancy].

In 16 normal and pathologic pregnancies we carried out the dehydroepiandrosterone-sulphate loading test by injection of 50 mg DHEA-S-Na intravenously. The plasma concentrations of unconjugated estradiol and estriol were measured by radioimmun-assay. The level of estradiol increased continuously, rising to a maximum 60 min after the injection. In pre-eclamptic patients and cases of intrauterine growth retardation the rise was significantly reduced. There was a good correlation between result of the test and clinical dates. In plasma concentrations of unconjugated estriol no changes could be observed within 3 hours after the injection.

Dehydroepiandrosterone↗

[Postmenopausal vaginal atrophy and topical therapy with an estriol-based ointment (Colpogyn): authors' experience].

The paper reports the results of a study to assess the efficacy of an estriol-based cream (Colpogyn) in the topical treatment of postmenopausal vaginal atrophy. 0.5 mg of estriol were applied daily for 10 consecutive days and three times a week for 2 weeks. Trophism of vaginal epithelium appeared to be better than that obtained using cream containing excipients alone. The excellent tolerability of this therapy enables urogenital dystrophy to be treated with optimum results.

Adult↗

Cloning and expression of human liver UDP-glucuronosyltransferase in COS-1 cells. 3,4-catechol estrogens and estriol as primary substrates.

The human cDNA clone, UDPGTh-2, encoding a liver UDP-glucuronosyltransferase (transferase) was isolated from a lambda gt11 cDNA library by hybridization to the mouse transferase cDNA clone, UDPGTm-1 (Kimura, T., and Owens, I. S. (1987) Eur. J. Biochem.168, 515-521). The two clones have nucleotide sequence identities in the coding region of 74%. UDPGTh-2 encodes a 529-amino acid protein with an NH2 terminus membrane-insertion signal peptide and a carboxyl terminus membrane-spanning region. There are three potential asparagine-linked glycosylation sites at residues 67, 68, and 315. In order to establish substrate specificity, the clone was inserted into the pSVL vector (pUDPGTh-2) and expressed in COS-1 cells. The presence of a transferase with Mr congruent to 52,000 in transfected cells cultured in the presence of [35S]methionine was shown by immunocomplexed products with goat antimouse transferase IgG (Mackenzie, P. I., Hjelmeland, L. H., and Owens, I. S. (1984) Arch. Biochem. Biophys. 231, 487-497) and protein A-Sepharose and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The transferase is a glycoprotein as indicated by a shift in Mr congruent to 3000-4000 when expressed in the presence of tunicamycin. Sixty potential substrates were tested using cells transfected with pUDPGTh-2. The order of relative substrate activity was as follows: 4-hydroxyestrone greater than estriol greater than 2-hydroxyestriol greater than 4-hydroxyestradiol greater than 6 alpha-hydroxyestriol greater than 5 alpha-androstane-3 alpha,11 beta,17 beta-triol = 5 beta-androstane-3 alpha,11 beta,17 beta-triol. There were only trace amounts of glucuronidation of 2-hydroxyestrone and 2-hydroxyestradiol, and, in contrast to other cloned transferases, no glucuronidation of either the primary estrogens/androgens (estrone, 17 beta-estradiol/testosterone, androsterone) or any of the exogenous substrates tested. A Lineweaver-Burk plot of the effect of 4-hydroxyestrone concentration on the velocity of glucuronidation shows an apparent Km of 13 microM. The unique specificity of this transferase for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites.

Amino Acid Sequence↗

A comparative study of longitudinal and cross-sectional changes in plasma levels of prolactin and estriol during normal pregnancy.

Plasma prolactin (PRL) and total estriol levels were measured in normal pregnant women using blood samples collected from different patients at different gestational ages (cross-sectional study) and samples collected from the same patient at different gestational ages (longitudinal study). The cross-sectional study showed that PRL exhibited an ascending curve, with a tendency towards increased sample variability as pregnancy progressed. The longitudinal study showed that the slopes of the curves for the isolated cases differed according to the phase of gestation, in contrast to what was suggested by the cross-sectional study. A positive relationship between estriol and PRL was observed.

Adolescent↗

Gas-liquid chromatographic method for determining urinary estriol, with 6 alpha-hydroxyestriol as internal standard.

I describe a chromatographic procedure for quantification of urinary estriol in late pregnancy, with 6 alpha-hydroxyestriol used as internal standard. The hydrolyzed sample is successively passed through a Bond Elut C18 column and a DEAE-Sephadex column. The estrogens are then completely resolved as silyl ethers on a packed gas-liquid chromatographic (GLC) column in isothermal mode. Analytical recoveries of conjugated estriol ranged between 96 and 102%. Between-day precision (CV) was 4.4% at a mean concentration of 85.1 mumol/L. Specificity was assessed by comparing results obtained with a capillary GLC column.

Chromatography, Gas↗

[Effect of local estriol therapy on the urethral pressure profile in the postmenopausal period].

Measurements of the pressure in the urethra were performed under standardized conditions with the aid of perfused catheters in 20 fertile and 20 postmenopausal women, from it 12 women after local estrogen therapy by means of Ostriol-Ovula. Hormone-cytological swabs from the urethra, vagina and from the urinary cells were done. Proliferation of the urogenital epithelialia under the estriol-therapy and an ascent of the MUP and MUCP in the urethra pressure profile under resting conditions could be achieved. The maximum of the pressure profile could be displaced proximaly. In the urethra pressure profile the distal pressure transmission increased. Estriol therapy was without secondary effects and is suitable for the conservative therapy of the stress incontinence type I to III.

Administration, Intravaginal↗