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PubMed1986

Hormones and cervical ripening: dehydroepiandrosterone sulfate, estradiol, estriol, and progesterone.

Fetal adrenal steroids have been shown to be important in the timing of parturition. Since dehydroepiandrosterone sulfate is converted to estrogen, which is important in cervical softening, levels of dehydroepiandrosterone sulfate together with those of estradiol, estriol, and progesterone were measured and compared in pregnant women undergoing induction of labor with ripe and unripe uterine cervices. While there were no differences between the levels of estradiol, estriol and progesterone in the two groups of women, dehydroepiandrosterone sulfate was significantly elevated in the group of women with ripe cervices. These findings suggest that cervical changes preceding the onset of labor are associated with a significant elevation of maternal dehydroepiandrosterone sulfate levels. Changes in maternal plasma estradiol, estriol, and progesterone levels do not appear to be clinically related to cervical ripeness.

Cervix Uteri↗
PubMed1992

Maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol levels in midtrimester trisomy 18 pregnancies.

OBJECTIVE: The purpose was to evaluate the levels of maternal serum human chorionic gonadotropin, alpha-fetoprotein, and unconjugated estriol in trisomy 18 pregnancies compared with normal singleton pregnancies. STUDY DESIGN: Sera from 14 trisomy 18 pregnancies (13 retrospectively and one prospectively ascertained) were analyzed for human chorionic gonadotropin, alpha-fetoprotein, and unconjugated estriol. RESULTS: The alpha-fetoprotein levels in the 10 trisomy 18 pregnancies without open neural tube or ventral wall defect had a median of 0.65 multiple of the median, although two had alpha-fetoprotein levels above 2.5 multiples of the median. The human chorionic gonadotropin levels had a median of 0.32 multiple of the median and the unconjugated estriol levels had a median of 0.56 multiple of the median. Although most women with trisomy 18 pregnancies had serum human chorionic gonadotropin levels that were less than 1.0 multiple of the median, three had markedly elevated human chorionic gonadotropin levels (greater than 5.0 multiples of the median). CONCLUSION: Our data are partially consistent with those previously published but suggest the possibility of a bimodal distribution of alpha-fetoprotein and human chorionic gonadotropin levels in trisomy 18-affected pregnancies, unrelated to a neural tube or abdominal wall defect. The efficiency of screening for trisomy 18 prospectively, using the three serum markers, requires further evaluation.

Adult↗
PubMed1985

Bioluminescent enzyme immunoassay for estriol. Use of reversibly inactivated bacterial luciferase as label.

A bioluminescent enzyme immunoassay using estriol labeled with reversibly inactivated bacterial luciferase is described. An estriol derivative bearing an alkylthiolsulfonate is linked to the cysteinyl thiols of luciferase by formation of mixed disulfide linkages; thus, luciferase becomes inactive. After immunoassay, the inactive luciferase of the label bound to the immunoprecipitate is reactivated by incubation with dithiothreitol and the luciferase activity then is quantitated by a 20-s reaction performed with an automated luminometer (LKB 1251). Under the defined conditions, the labels are stable for at least 14 days as tested at 4 degrees C. A standard curve with a wide linear range from 50 to 6000 pg is demonstrated. This unique technology discussed here, therefore, offers exciting possibilities as a sensitive and rapid enzyme immunoassay for estriol.

Estradiol↗
PubMed1990

Characterization and primary sequence of a human hepatic microsomal estriol UDPglucuronosyltransferase.

A human liver microsomal UDP glucuronosyltransferase (UDPGT) that demonstrates reactivity with estriol (pI 7.4 UDPGT) has been purified to homogeneity and characterized further. No activity toward morphine, 4-hydroxybiphenyl, bilirubin, or tripelennamine was observed. The estriol UDPGT shows immunoreactivity with antibodies raised against rat hepatic microsomal 3 alpha- and 17 beta-hydroxysteroid UDPGTs but not with antibodies raised against rat hepatic microsomal p-nitrophenol UDPGT. The NH2-terminal sequence of the purified protein was determined and found to correspond to an identical sequence in the deduced amino acid sequence of a cDNA obtained from a human liver library in lambda gt11 (HLUG4). Sequence analysis revealed that HLUG4 is 2094 bp in length and encodes a protein of 523 amino acids which has a 16 amino acid leader sequence, followed by an untranslated 3' region of 525 bp. Three potential N-glycosylation sites were identified in the predicted sequence. The deduced amino acid sequence of estriol UDPGT showed 82% identity with the deduced amino acid sequence of another human hepatic cDNA (HLUG25), which has been expressed as a UDPGT capable of 6 alpha-hydroxyglucuronidation of hyodeoxycholic acid, strongly suggesting that these proteins are members of the same gene subfamily.

Amino Acid Sequence↗
PubMed1975

Measurement by radioimmunoassay of unconjugated estriol in pregnancy serum.

Antisera to estriol 6--onjugates were tested for suitability in the direct radioimmunoassay of unconjugated estriol in extracts of pregnancy serum. Assessment of specificity through titration with competing steroids allowed a selection to be made within the group of antisera. The measurement was then standardized by checking the absence of analytical blank (solvent and sample blank) and the extent of binding variability associated with the use of charcoal-dextran as a separating agent. Validation was made by means of the usual recovery and dilution tests, and by a cross-comparison of analytical data obtained with different antisera; reproducibility of calibration curve and within-and between-assay variability was evaluated under routine conditions. The validity of the clinical information was assessed by assaying 202 samples randomly collected throughout normal pregnancy from the 16th week to term: both trend and levels of unconjugated estriol concentration were found to be in good agreement with the literature data.

Animals↗
PubMed1984

Estriol modifies the absorption of estrone and estradiol in castrated rhesus monkeys: a new therapeutic approach for the use of natural estrogens in the menopause?

In order to study the effects of estriol (E3) on estradiol (E2) and estrone (E1) absorption in the rhesus monkey the following study was performed. Chronically ovariectomized animals were divided in four groups of five each according to the treatment protocol (1) E1: 0.7 mg (2) E1: 0.7 mg + E3: 0.135 mg (3) E2: 0.3 mg, (4) E2: 0.3 mg + E3: 0.135 mg (5) E1: 0.7 mg + E2: 0.3 mg and (6) E1: 0.7 mg + E2: 0.3 mg + E3: 0.135 mg. Monkeys received daily drug administration (DA) for 10 consecutive days. Serum E1, E2 and E3 were determined by RIA on a daily basis. In addition, during the first day of treatment blood samples were obtained at hourly intervals. Results were analyzed by comparing the areas under the curve (Integral tests). The data shows that during treatment serum concentrations of E1 and E2 in groups 1, 3 and 5 were significantly higher than in groups 2, 4 and 6 (2-4-fold greater). Serum levels of E1 and E2 rose 5-fold from baseline in animals from group 1 within 1 h, while they increased only 2-fold in those from group 2 at 3-6 h after DA. Similarly, serum levels of E1 and E2 increased 30- and 10-fold respectively 1 h after DA in group 3, while they rose 12- and 5-fold respectively 4 h after DA in animals of group 4. Estriol levels were similar in animals from group 2 and 4 throughout the study (250 +/- 80 pg/ml). It may be concluded therefore that the oral administration of estriol diminishes the absorption of both E1 and E2 and alters their bioavailability, perhaps modulating their biological activity.

Absorption↗
PubMed1983

The effect of oral estriol succinate therapy on the endometrial morphology in postmenopausal women: the significance of fractionation of the dose.

Postmenopausal women were given estriol succinate orally in a daily dose of 4 mg X 2 for 14 days or 4 mg X 2, 8 mg X 1 and 2 mg in the morning + 2 mg at noon + 4 mg in the evening for 4 wk. Each group consisted of 4 women. The effect of the estrogen treatment was estimated by the endometrial curettage samples taken both before and after the hormone treatment. The curettage samples were studied by both light and electron microscopy. The results showed that a treatment period of 4 wk was necessary to obtain any effect. When 8 mg of estriol succinate was given in a single dose only a slight effect was obtained on the endometrium but when the same dose was divided in 2 daily 4 mg parts, the endometrium showed clearly proliferative changes. Thus estriol is able to produce the same endometrial effect as estradiol. Ultrastructurally the hormone treatment caused an increase in the cytoplasm of the endometrial epithelial cells. Also, whorls of cytoplasmic microfilaments often appeared near the nucleus of the cells.

Aged↗
PubMed1984

Placental lactogen, progesterone, total estriol and prolactin plasma levels in pregnant women with insulin-dependent diabetes mellitus.

Fifteen insulin-dependent diabetic (White's class B-C) and 10 healthy pregnant women were examined from the 12th to the 36th wk. Every 4 wk, a blood sample was drawn to determine total estriol, progesterone, placental lactogen and prolactin. Throughout the pregnancy, total estriol and progesterone in diabetic and non-diabetic women are very similar. On the contrary, the PRL levels are constantly lower in diabetic pregnant women, even though the difference is statistically significant only for the 24th wk determination. The hPL level is instead significantly lower in diabetic pregnant women at the 12th, 20th, 24th, 32nd and 36th wk. A negative correlation exists between the hPL value and the mean blood glucose level, performed the same day as the hormonal test. This correlation is statistically significant at the 12th, 16th, 20th, 28th and 36th wk. No significant difference is found between the two groups examined for the delivery week, the placental weight, the birth weight and the fetal body weight index. To conclude, while estriol and progesterone are not affected by the higher variability of glucose levels during pregnancy in diabetics, compared to normals, hPL and perhaps also PRL may be influenced by the mild hyperglycemia consequent to diabetes.

Adult↗
PubMed1993

The effect of estriol on the cytology of urethra and vagina in postmenopausal women with genito-urinary symptoms.

In a double-blind, randomised trial, 62 postmenopausal women with genito-urinary symptoms were treated with oestriol or matching placebo for 4 weeks. Estriol (Synapause-E3, Nourypharma Nederland) was given orally for 4 weeks in a single daily dose (8 mg/day first week, 4 mg/day second and third week, 2 mg/day fourth week). The influence of estriol on the vaginal and urethral epithelium was assessed by using the karyopycnotic index and the maturation value. As we expected, it was confirmed that estriol has a remarkably beneficial effect on the vaginal epithelium. This also applies to the epithelium of the urethra, although the effect is much less obvious.

Aged↗
PubMed1976

A rapid specific radioimmunoassay for unconjugated estriol in plasma.

A rapid, non-chromatographic radioimmunossaay for unconjugated estriol in pregnancy plasma has been developed which utilizes a commonly available antiestrogen antisera. Estradiol-17beta and estrone demonstrate 135% relative cross-reactivity with our antiserum, as compared with 100% for estriol. Specificity is achieved by purification of estriol with solvent partitioning using benzene: petroleum ether (1:1). The results obtained using this method are similar to a radioimmunoassay utilizing a highly specific, but commercially unavailable, antiestriol antiserum. The method is precise, with coefficients of variation ranging from 3.0 to 8.2%.

Antibody Specificity↗
PubMed1983

Salivary unconjugated estriol levels in normal third trimester pregnancy - direct correlation with serum levels.

A radioimmunoassay for salivary unconjugated estriol concentration during the third trimester of normal pregnancy is described. The performance characteristics of the method were established by determining the non-specific binding, the blank value of the endogenous estriol free ("stripped") saliva, the recovery experiment and intra- and interassay coefficient of the variations. The corresponding serum samples were also analyzed by the same method. An excellent correlation was found between salivary and serum estriol concentrations.

Estriol↗
PubMed1984

Specific antisera for the radioimmunoassay of estriol 3-sulfate.

Antisera were raised in male guinea pigs against 6-oxoestriol 3-sulfate O-carboxymethyloxime-bovine serum albumin (BSA) conjugate. The antisera to this antigen exhibited high affinity (Ka=4.7 X 10(9)M-1) and excellent specificity for estriol 3-sulfate, showing slight cross-reactions (less than 0.43%) with other estrogen sulfates, and no cross-reactivities with free estrogens and other steroids (less than 0.01%) except cholesterol sulfate (0.22%). A standard curve using [6, 7-3H]-estriol 3-sulfate as the radioactive ligand showed high sensitivity in the range of 10-1000 pg estriol 3-sulfate.

Animals↗
PubMed1978

The effect of estriol succinate therapy on plasma renin activity and urinary aldosterone in postmenopausal women.

The effects of estriol succinate (Synapause, 2 mg daily) on the renin-aldosterone system and blood pressure (RR) were studied in 14 postmenopausal women after bilateral oophorectomy. Plasma renin activity (PRA) and daily urinary aldosterone excretion (dU-Ald) were determined 1 mth after the operation and before estrogen treatment, at the end of 2 mth therapy, and, for the third time, 2 mth after the termination of treatment with the drug. No changes in PRA, dU-Ald or RR were found in normotensive women, or in 3 women with hypertension in this group. Another group of 11 postmenopausal women was investigated after long-term estriol succinate therapy, which had lasted for 5-8 yr after oophorectomy. PRA, dU-Ald and RR were measured during treatment and 2 mth after terminating the therapy. No changes were found either in hormone differences in the mean levels of PRA or dU-Ald. The results suggest that estriol succinate is devoid of general harmful effects on the renin-aldosterone system during postmenopausal therapy for climacteric symptoms.

Aldosterone↗
PubMed1995

Transvaginal estriol administration in postmenopausal women: a double blind comparative study of two different doses.

A group of 72 postmenopausal women were treated for 4 weeks with vaginal suppositories containing 0.5 or 1.0 mg of estriol. The two different doses achieved an identical significant improvement of urogenital symptoms, while a dose-related effect seen to be on climacteric complaints, according to a good absorption of estriol by the vaginal epithelium. Minimal side effects were observed and the safety of vaginal estriol treatment could advise further study about the effect of this kind of treatment on the climacteric syndrome.

Administration, Intravaginal↗
PubMed2004

Estriol treatment ameliorates disease in males with experimental autoimmune encephalomyelitis: implications for multiple sclerosis.

Estrogen treatment has been found to be protective in experimental autoimmune encephalomyelitis (EAE) and possibly multiple sclerosis (MS). We investigated whether the effect of estrogen treatment is gender-specific. Estrogen receptor (ER) expressions, ERalpha and ERbeta, were found to be equivalent in both genders. EAE disease severity in both females and males was decreased with estriol treatment as compared to placebo. Finally, proinflammatory cytokine production during autoantigen-specific immune responses was decreased with estriol treatment in both females and males. These data support a potential role for estriol treatment for men in addition to women with MS.

Analysis of Variance↗
PubMed2004

Estriol bound and ligand-free structures of sterol 14alpha-demethylase.

Sterol 14alpha-demethylases (CYP51) are essential enzymes in sterol biosynthesis in eukaryotes and drug targets in antifungal therapy. Here, we report CYP51 structures in ligand-free and estriol bound forms. Using estriol as a probe, we determined orientation of the substrate in the active site, elucidated protein contacts with the invariant 3beta-hydroxy group of a sterol, and identified F78 as a key discriminator between 4alpha-methylated and 4alpha,beta-dimethylated substrates. Analysis of CYP51 dynamics revealed that the C helix undergoes helix-coil transition upon binding and dissociation of a ligand. Loss of helical structure of the C helix in the ligand-free form results in an unprecedented opening of the substrate binding site. Upon binding of estriol, the BC loop loses contacts with molecular surface and tends to adopt a closed conformation. A mechanism for azole resistance in the yeast pathogen Candida albicans associated with mutations in the ERG11 gene encoding CYP51 is suggested based on CYP51 protein dynamics.

Amino Acid Sequence↗
PubMed1999

A role for estriol in human labor, term and preterm.

Although estriol has been studied as an indicator of fetal well-being in the past, its broader biologic role has not been elucidated. Estriol in the maternal compartment closely reflects fetal adrenal activity, and increased fetal adrenal activity prior to the onset of labor is a common link in mammalian parturition. In humans, estriol increases before spontaneous labor and may be a clinically useful marker for some cases of preterm labor.

Animals↗