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PubMed1997

Molecular and kinetic basis for the mixed agonist/antagonist activity of estriol.

Estriol acts as a weak estrogen when administered in a single dose into immature or ovariectomized laboratory animals, but produces full estrogenic responses upon chronic administration. However, when estriol is injected together with estradiol it acts as an antiestrogen. We studied the dual agonist/antagonist properties of estriol, using recombinant human estrogen receptor (hER) in ligand-binding assay, cell-free transcription assay, electrophoretic mobility shift assay with cVitII estrogen response element (ERE), and ERE-Sepharose chromatography. We show that the weak estrogenic activity of estriol results from impaired hER-ERE interaction. The antiestrogenic activity of estriol was demonstrated in a cell-free transcription assay where it reduced estradiol-dependent transcription in a dose-dependent manner. Estriol interfered with estradiol-induced positive cooperative binding and receptor dimerization, and binding of hER complexes to ERE. These effects of estriol were maximal at a 10-fold molar excess over estradiol; under these conditions estradiol-dependent transcription was decreased by 85%, although [3H]estradiol binding was reduced by only 50%. We propose that when hER, estradiol, and estriol are coequilibrated, several receptor species are formed: unliganded hER monomers and dimers; estradiol-hER monomers and dimers, estriol-hER monomers and dimers; and presumably mixed estradiol-estriol dimers. Since estrogen-hER complexes bind cooperatively to ERE sequences, the concentrations of transcriptionally active complexes (estriol- and estradiol-hER dimers) are reduced to low levels that fail to bind cooperatively with ERE and initiate transcription. We discuss our results in relation to the massive estriol production during pregnancy and to the "Estriol Hypothesis" on the protective role for estriol in opposing carcinogenic effects of estradiol.

Cell-Free System↗

PubMed1979

An enzyme-immunoassay for estriol.

A practical method was developed for enzyme-immunoassay of serum estriol, with alkaline-phosphatase as a marker enzyme. Alkaline-phosphatase was conjugated with estriol-6-(O-carboxymethyl) oxime using water soluble carbodiimide. The estriol-alkaline-phosphatase complex, which has both enzyme activity and capacity to bind anti-estriol serum, was obtained by Sephadex G-200 gel filtration. This complex, which was stable for at least 3 months at 4 degrees C, was used as enzyme-labelled estriol. Anti-estriol serum raised against estriol-6-(O-carboxymethyl) oxime bovine serum albumin was employed. "Bound and free" estriol were separated by the double antibody method. A linear relation was obtained between estriol concentration and antibody-bound alkaline-phosphatase activity in the range of 0.2-100 ng estriol/ml. In this assay system, cross-reactivity with other steroids was negligible under physiological conditions, and endogenous alkaline-phosphatase, which increases during the late pregnancy, caused no interference. The coefficients of variation were 3.3-14.2% (within assays), and less than 22% (between assays), and the mean recovery rate was 77.5%. Serum estriol values determined by the present method correlated well with those determined by radioimmunoassay (r=0.90 for total estriol; r=0.98 for free estriol). The present method of enzyme-immunoassay is suitable for measurement of serum estriol during pregnancy.

Alkaline Phosphatase↗

PubMed1984

Estriol: absorption after long-term vaginal treatment and gastrointestinal absorption as influenced by a meal.

This study was designed to evaluate the vaginal absorption of estriol when given as a 21-day treatment. Vaginal absorption was compared with the oral absorption of a known estriol preparation (TriovexR, Leo AB, Sweden). One mg of estriol was administered intravaginally once a day for 21 days to 6 menopausal women. Plasma concentrations of unconjugated estriol were measured by a specific RIA-method at frequent intervals during 24 hours on the first and 21st day of treatment. One month later, 10 mg of estriol was given once orally and plasma estriol concentrations were measured in the same way. At vaginal administration, the absorption of estriol was very effective. When measured on the 21st day, the absorption had declined significantly but was still nearly in the same range as after oral administration of 10 mg of estriol. At oral administration, there was an initial plasma estriol elevation for 3 hours only followed by a second one immediately postprandially. It is concluded that estriol is readily absorbed from the vagina, but the absorption does decline significantly during prolonged treatment. A large single oral dose of estriol provides initially a high plasma estriol concentration but also a second one induced by eating a meal, possibly indicating an enterohepatic recirculation of estriol.

Administration, Oral↗

PubMed2001

Changes in rates of salivary estriol increases before parturition at term.

OBJECTIVE: The aim of this study was to characterize the increases of salivary estriol concentrations before the onset of labor at term. STUDY DESIGN: Salivary estriol concentrations were measured in weekly patient-collected samples by means of a sensitive (mean +/- SD threshold, 0.025 +/- 0.001 ng/mL; coefficient of variation, 3.8%) direct enzyme immunoassay in a microtiter plate format. The salivary estriol concentrations in 16 healthy pregnant women were characterized from 30 weeks' gestation until the time of parturition and delivery. Samples were stored frozen at collection and analyzed in batches after delivery. RESULTS: The median salivary estriol concentration profile revealed a nonlinear rise beginning from 30 weeks' gestation (0.89 ng/mL) until term (2.70 ng/mL, an increase of 201%). At 35 weeks' gestation the salivary estriol concentration median value increased sharply (positive inflection point, 50%-93% increase) at a demarcation between a slower increase during early pregnancy and a more rapid increase during late pregnancy. This positive inflection point associated with a late pregnancy increase characterized subgroups of pregnancies according to the lengths of gestation as follows: early term (delivered at <38 weeks 1 day's gestation), middle term (delivered at 38 weeks 1 day-40 weeks' gestation), and late term (delivered at >40 weeks' gestation). Five weeks before delivery the mean (+/-SEM) rate of rise in salivary estriol concentration was 0.50 +/- 0.13 ng/mL per week to 0.84 +/- 0.26 ng/mL per week in the early term group. The increase in rate for the middle term group was 0.32 +/- 0.06 ng/mL per week to 0.37 +/- 0.26 ng/mL per week, whereas in the late term group the rate of salivary estriol concentration rise was 0.37 +/- 0.03 ng/mL per week to -0.03 +/- 0.25 ng/mL per week. CONCLUSION: These data demonstrate in normal pregnancies (1) that a direct, nonradiometric measure of salivary estriol concentration can be used to monitor the late pregnancy increase in estriol production, (2) that 35 weeks' gestation marks a positive inflection point of the onset of increased estriol production, and (3) that the late pregnancy rise in salivary estriol concentration shows distinct patterns that tend to be characteristic of the length of pregnancy. These data support the concept that the rate of increase of estriol production is related to the timing of the onset of labor.

Adult↗

PubMed1986

The current role of daily serum estriol monitoring in the insulin-dependent pregnant diabetic woman.

This retrospective analysis of the use of serum estriol levels for antenatal assessment was performed in an effort to determine if routine, late third-trimester, daily serum estriol monitoring of insulin-dependent pregnant diabetic women can still be justified. Estriol profiles of 170 diabetic pregnancies, managed under a consistent protocol of weekly contraction stress tests and daily serum estriol assessments, were reviewed. A total of 4612 estriol determinations were performed. Nearly 4% of the estriol determinations showed a 35% fall from the mean of the previous three highest consecutive values. Forty-seven percent of the patients had at least one fall of this magnitude. Eighty-five percent of the fetal heart rate tests performed in association with an estriol fall were normal. A fall in estriol was not found to be associated with a higher risk of having a positive contraction stress test, either at the time the estriol fall was recognized or at any time during the patient's antepartum course. Although use of this strict protocol combining the use of weekly contraction stress tests and daily serum estriol determinations provided a safe method of antepartum assessment, there is little evidence to support the routine use of daily serum estriol monitoring in insulin-dependent pregnant diabetic women.

Adult↗

PubMed1984

Estriol production and metabolism in normal women.

Studies on estriol metabolism and production were carried out in normal reproductive-aged and post-menopausal women using pulse injections and constant infusions of radiolabeled estriol, estrone and estradiol. The circulating levels were measured by radioimmunoassay. Following an intravenous pulse of [3H]estriol, the disappearance of radioactivity as estriol could be described as a function which was sum of two exponentials with t 1/2's of 3.6 and 64 min. The initial volume of distribution was 201. Using the constant infusion technique the metabolic clearance rate (MCR) of estriol was 2100 1/day in the follicular phase of the cycle and similar in the luteal phase. In postmenopausal women the MCR was 1890 1/day. The circulating levels of estriol were 7 and 11 pg/ml in the follicular and luteal phases respectively and 6 pg/ml in post-menopausal women. The production rates of estriol were 14 and 23 micrograms/day in the follicular and luteal phases of the cycle and 11 micrograms/day in post-menopausal women. In many of the women infused with radiolabeled estrone or estradiol, no radioactivity could be identified in the blood as estriol. The maximal conversion of estrone and estradiol was less than 0.4%. Estriol circulates at low but relatively steady levels in the blood. In some women estriol appears to be secreted by the ovary, especially in the luteal phase.

Adult↗

PubMed1984

The estriol-induced inhibition of the estrogen receptor's positive cooperativity.

The effect of estriol on the positive cooperativity of [3H]estradiol binding to the partially purified calf uterine estrogen receptor was investigated using the kinetic analysis of Sasson and Notides (J. biol. Chem. 257 1982, 11540). The receptor was titrated with variable concentrations of [3H]estradiol with or without estriol; the estriol was maintained in a constant molar ratio to the [3H]estradiol concentration. A 4-fold molar excess of estriol above the [3H]estradiol concentrations inhibited the receptor's cooperative [3H]estradiol binding. In the absence of estriol, the [3H]estradiol receptor interaction was highly cooperative, the Scatchard plot was convex and the Hill coefficient was 1.61 +/- 0.02. In the presence of sufficient estriol to reduce the maximally bound [3H]estradiol to 77%, the Scatchard plot was linear and the Hill coefficient was 1.04 +/- 0.04. The inhibition of the cooperative [3H]estradiol binding by estriol was not due to isotope dilution of the specifically bound [3H]estradiol by the unlabeled estriol. These data demonstrate that the cooperative binding of [3H]estradiol by the receptor that is characteristic of the equilibrium between the two states of the receptor (active and nonactive) is eliminated by the presence of estriol. This finding is consistent with the agonist/antagonist activity of estriol observed in vivo.

Animals↗

PubMed1985

Enzymeimmunoassay of unconjugated estriol in serum and saliva during pregnancy.

An enzymeimmunoassay (EIA) for unconjugated estriol was developed. Estriol-6-CMO-BSA was used as antigen for the antiserum production with low cross reactivities to estrone (0.3%) and estradiol (0.17%). The enzyme conjugate (estriol-peroxidase) was prepared using the mixed anhydride reaction. The antibody bound estriol fraction was separated from the free fraction with the double antibody technique. The test requires a simple photometer for the measurement of enzyme label. The developed estriol-EIA needs a short incubation time (2 hrs). The normal values of estriol in serum were determined. The results are in good agreement with the results of RIA. Furthermore, we found an inverse diurnal rhythm of serum and salivary estriol in comparison to the cortisol level. Low estriol levels in the morning and high estriol concentration in the evening are indices of fetal health. Decreased estriol levels in the morning of several days were found in pathological pregnancies (intrauterine fetal death, fetal distress, hepatose).

Circadian Rhythm↗

PubMed1999

Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis.

OBJECTIVE: To evaluate the use of estriol in the treatment of experimental autoimmune encephalomyelitis (EAE) and other cell mediated autoimmune diseases. BACKGROUND: Experimental autoimmune encephalomyelitis is a T helper 1 (Th1)-mediated autoimmune demyelinating disease that is a useful model for the study of immune responses in MS. Interestingly, both EAE and MS have been shown to be ameliorated during late pregnancy. METHODS: Estriol, progesterone, and placebo pellets were implanted in mice during the effector phase of adoptive EAE. Disease scores were compared between treatment groups, and autoantigen-specific humoral and cellular responses were examined. RESULTS: Estriol treatment reduced the severity of EAE significantly compared with placebo treatment whereas progesterone treatment had no effect. Estriol doses that induced serum estriol levels that approximated estriol levels during late pregnancy were capable of ameliorating disease. Estriol-treated EAE mice had significantly higher levels of serum antibodies of the immunoglobulin (Ig) G1 isotype specific for the autoantigen myelin basic protein (MBP). Further, MBP-specific T-lymphocyte responses from estriol-treated EAE mice were characterized by significantly increased production of the Th2 cytokine interleukin 10 (IL-10). T lymphocytes were shown to be the primary source of IL-10 within antigen-stimulated splenocyte populations. CONCLUSIONS: Estriol as a hormone involved in immune changes during pregnancy may provide a basis for the novel therapeutic use of estriol for MS and other putative Th1-mediated autoimmune diseases that improve during late pregnancy.

Animals↗

PubMed1981

Estriol- and estradiol-17 beta-induced luteinizing hormone release in ovariectomized cows and ewes.

Two studies were conducted with ovariectomized animals to compare luteinizing hormone (LH) responses during the 24-hr period following an IM injection of either estriol or estradiol-17 beta. In Exp. 1, six long-term ovariectomized (6 months) beef cows were randomly assigned to be given 1 mg of estriol or estradiol 17 beta injected in 4 ml of corn oil. Two months later, the experiment was replicated in a switch back design. In Exp. 2, eight ewes that had been ovariectomized for 1 to 4 months were randomly assigned to be given 150 micrograms of estriol or estradiol-17 beta injected in 1.5 ml of corn oil. The initial increase in serum LH concentrations occurred earlier in both cows (P less than .01) and ewes (P less than .05) in response to estriol (8 to 9 hr) than in response to estradiol 17 beta (12 to 18 hr). In addition, duration of the decrease in LH release that occurred 1 hr after estrogen injection in ewes was 3 hr shorter (P less than .05) in response to estriol than in response to estradiol-17 beta. The total area under the LH response curve was greater for both cows (P less than .05) and ewes (P less than .01) given estradiol-17 beta than for those given estriol. Administration of estradiol-17 beta induced a 10-fold increase in serum estradiol-17 beta concentrations and a two to fourfold increase in serum estrone concentrations. Both estrogens returned to basal concentrations by 24 hr after administration. Peak serum estriol exceeded 300 pg/ml within 1 hr of estriol injection, but decreased to nondetectable levels within 12 hours. We concluded that estriol can stimulate LH release from the pituitary. Furthermore, the differential LH response to the two estrogens suggests that the positive effects of estriol are mediated earlier but that estradiol-17 beta is a more potent stimulus when administered as a single IM injection.

Animals↗

PubMed1987

[Synthesis and metabolism of estriol conjugates].

As an indicator of fetal well being, the urinary estriol value is widely utilized. But the discrepancy between the results of NST and urinary estriol value has recently been pointed out. The estimation of plasma estriol is also recommended as a more reliable means of fetal assessment than that of urinary estriol. The purpose of the study is to clarify the patterns of estriol conjugates in maternal blood, retroplacental blood and cord blood, and further to elucidate the metabolism and secretion of each conjugate in organs and to determine the most useful conjugate as a source of fetal information. In normal pregnancy urine, estriol glucosiduronate is the dominant component of urinary estriol. In preeclampsia, the percentage of G decreased and that of G-S increased. In retroplacental blood, G-S is the main conjugate. On the other hand in cord blood, S is the dominant conjugate. The placental perfusion experiment revealed that the placenta hydrolyzed each conjugate to a free form and did not convert one conjugate to another. Periodical determination of plasma estriol conjugates in pregnant women revealed that the G-S fraction fluctuated most during parturition. The importance of liver as a possible site for estriol conjugation and the role of kidney in selective clearance of estriol conjugates are discussed.

Estriol↗

PubMed2003

Plasma surgery and topical estriol: effects on the nasal mucosa and long-term results in patients with Osler's disease.

OBJECTIVE: The study goal was to report on the long-term results and effect of argon plasma coagulation (APC) surgery and topical estriol in patients with Osler's disease who had recurrent epistaxis. Study design In a prospective clinical study, 52 patients underwent APC and estriol application and were followed for 18 months regarding their bleeding frequency and intensity. Patient blood samples were obtained to determine the serum estriol levels. Scanning electron microscopy of the nasal mucosa enabled a better understanding concerning the effect of estriol on the nasal mucosa. RESULTS: Eighteen months after treatment, 96% of the patients stated a significantly reduced bleeding frequency and intensity. Under estriol influence, former berry-like telangiectasia of the nasal mucosa was flatter. The serum estriol levels did not increase significantly in any of the patients. No side effects from the use of topical estriol were observed. CONCLUSION: The combined treatment approach with APC and topical estriol significantly reduces epistaxis in Osler's disease. SIGNIFICANCE: APC and topical estriol have proved to be a promising alternative in the treatment of Osler's disease.

Adolescent↗

PubMed1993

A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections.

BACKGROUND: Recurrent urinary tract infections are a problem for many postmenopausal women. Estrogen replacement restores atrophic mucosa, lowers vaginal pH, and may prevent urinary tract infections. METHODS: We enrolled 93 postmenopausal women with a history of recurrent urinary tract infections in a randomized, double-blind, placebo-controlled trial of a topically applied intravaginal estriol cream. Midstream urine cultures were obtained at enrollment, monthly for eight months, and whenever urinary symptoms occurred. Vaginal cultures and pH measurements were obtained at entry and after one and eight months. The women were assigned to receive either estriol (n = 50) or placebo (n = 43), both administered intravaginally; 36 and 24, respectively, completed the eight months of follow-up. RESULTS: The incidence of urinary tract infection in the group given estriol was significantly reduced as compared with that in the group given placebo (0.5 vs. 5.9 episodes per patient-year, P < 0.001). Survival analysis showed that more of the women in the estriol group than in the placebo group remained free of urinary tract infection (P < 0.001). Lactobacilli were absent in all vaginal cultures before treatment and reappeared after one month in 22 of 36 estriol-treated women (61 percent) but in none of the 24 placebo recipients (P < 0.001). With estriol the mean vaginal pH declined from 5.5 to 3.8 (P < 0.001), whereas there was no significant change with placebo. The rate of vaginal colonization with Enterobacteriaceae fell from 67 percent to 31 percent in estriol recipients but was virtually unchanged (from 67 to 63 percent) in the placebo recipients (P < 0.005). Side effects were minor, but caused 10 estriol recipients (28 percent) and 4 placebo recipients (17 percent) to discontinue treatment. CONCLUSIONS: The intravaginal administration of estriol prevents recurrent urinary tract infection in postmenopausal women, probably by modifying the vaginal flora.

Administration, Intravaginal↗

PubMed2002

Plasma corticotropin-releasing hormone and unconjugated estriol in human pregnancy: gestational patterns and ability to predict preterm delivery.

OBJECTIVE: The purpose of this study was to compare the patterns and timing of the increases in plasma levels of corticotropin-releasing hormone and unconjugated estriol during human pregnancy. STUDY DESIGN: Corticotropin-releasing hormone and unconjugated estriol were measured in serial samples that were collected from preterm subjects and from spontaneous term control subjects who were selected randomly from a study cohort of 297 women. RESULTS: Gestational increases in log corticotropin-releasing hormone and log unconjugated estriol concentrations were best described by linear and cubic polynomial functions, respectively. Plasma unconjugated estriol levels were similar in preterm and term singleton pregnancies at equivalent gestation, whereas corticotropin-releasing hormone was elevated earlier in premature subjects. Mean corticotropin-releasing hormone levels relative to term control subjects (n = 40 women) were shifted forward 16.5 +/- 8.1 days (P =.027, singleton preterm, spontaneous labor; n = 16) and 33.0 +/- 7.9 days (P <.001, singleton preterm, obstetric intervention; n = 10). The corresponding shifts in unconjugated estriol values were -3.8 +/- 2.0 days and -2.7 +/- 5.6 days (both not significant). The prematurity of delivery showed a significant regression on shifts in corticotropin-releasing hormone (P =.004 and P <.001) but not in unconjugated estriol for the 2 groups. The ability to predict prematurity was not significantly improved by regression on corticotropin-releasing hormone and unconjugated estriol shift values together. CONCLUSION: The patterns and timing of gestational changes in corticotropin-releasing hormone and unconjugated estriol differ in humans. The usefulness of corticotropin-releasing hormone as a biochemical preterm marker in singleton pregnancies is not enhanced by the additional measurement of plasma unconjugated estriol.

Corticotropin-Releasing Hormone↗

PubMed1976

The metabolic clearance and blood production rates of estriol in normal, non-pregnant women.

The metabolic clearance rate (MCR) and blood production rate (PB) of estriol have been measured in normal, non-pregnant women 21 to 65 years old. 6,7-3H-Estriol was administered as a pulse injection to 4 women between days 5-7 of their menstrual cycle. The disappearance of radioactivity as unconjugated estriol can be described as a function which is the sum of two exponentials. The initial component represents spread into and transfer from a space with a volume of 20.6 +/- 5.4 (SE) l. The mean value for the rate constant of total removal (reversible and irreversible) was 290.2 +/- 78.5 units/day of which 0.34 +/- 0.06 was irreversible. The mean MCRR was 990 +/- 70 l/day/m2. 4-14C-Estriol was infused at a constant rate for 3 1/2 hours to 13 women between days 5-7 of their cycle. The mean MCR was 2,100 +/- 100 l/day or 1,240 +/- 40 l/day/m2. Thirteen women received a constant infusion of 4-14C-estriol between days 20-22 of their cycle. The mean MCR was 2,100 +/- 115 l/day or 1,280 +/- 65 l/day/m2. The mean values for the two phases of the cycle were not significantly different (P greater than 0.1). The mean value for the MCR in 4 post-menopausal women studied in similar fashion was 1,890 +/- 95 l/day or 1,060 +/- 35 l/day/m2. The mean concentrations of estriol were 7.0 +/- 0.7 and 10.9 +/- 0.8 in the follicular and luteal phases of young women, respectively. The mean PB for women in the follicular phase was 14.0 +/- 1.6 mug/day and in the luteal phase was 22.7 +/- 1.9 mug/day. These values were significantly different (P less than 0.01). When the PB's for the 11 women studied in both phases of the cycle were compared the luteal phase values were significantly higher 0.02 greater than P greater than 0.01) using the paired t test. The PB in the 4 post-menopausal women ranged from 5 to 22 mug/day. While there was no difference between the MCR of estriol measured in the two phases of the cycle, the PB of estriol was significantly greater in the luteal phase. Estriol probably contributes little to the overall estrogenic activity in normal, non-pregnant, premenopausal women but could make a more significant contribution in some post-menopausal women.

Adult↗

PubMed2000

Ovarian follicular fluid contains immunoreactive estriol: lack of correlation with estradiol concentrations.

Estradiol and estrone concentrations in ovarian follicular fluid change according to the ovulatory cycle, but no studies on the possible presence and/or changes of estriol are available. The aim of the present study was to evaluate whether estriol is measurable in follicular fluid and how its concentration changes according to the volume of ovarian follicles and to the maturational stage of oocytes. A group of women (n = 39) undergoing a program of induction of ovulation was included in this study and divided into three groups according to the causes of infertility: those with unexplained infertility (n = 11); those with endocrine disturbances (n = 5); and normal ovulatory women (n = 23) (controls). The follicles recruited (n = 116) on the basis of morphology and the appearance of the oocyte cumulus-corona complex were divided into: mature (n = 22); intermediate (n = 75); immature (n = 11); and atretic (n = 8). Ovarian follicles were also divided according to the diameter of each: < 1.5 cm (n = 38); 1.6-2.4 cm (n = 66); and > 2.5 cm (n = 12). Ovarian follicular fluids were aspirated under ultrasound guidance and a blood specimen was collected from each subject. Estriol and estradiol concentrations were evaluated by radioimmunoassay in serum and follicular fluid following an ether extraction. Estriol was found in high concentration in each sample of follicular fluid, significantly higher than in the respective serum sample (p < 0.01). Although the estradiol concentration was significantly lower in follicles containing immature and atretic oocytes than in intermediate or mature follicles (p < 0.01), the estriol concentration did not depend upon the maturational stage. In addition, the follicular fluid estriol concentration did not differ according to the causes of infertility. Follicular fluid and serum estradiol concentrations showed significant correlation (p < 0.01), whereas no significant correlation was observed between serum and follicular estriol concentrations. The present data show that follicular fluid contains a high concentration of estriol and that its changes are independent of the ovulatory cycle and estradiol concentrations, supporting an independent origin and suggesting a different function for estriol.

Estradiol↗

PubMed2005

The effects of topical estriol and vehicle cream on the mechanical and histological properties of normal rat skin.

BACKGROUND: The biomechanical and histological effects of topical estriol in normal rat skin are not clearly defined, although several favourable effects of estrogens have been suggested, especially in the postmenopausal period. Our goal was to determine whether estrogens have any such effects on skin histology and biomechanical properties in an experimental rat model. MATERIAL/METHODS: Estriol cream or vehicle cream was topically applied to the dorsum of Sprague Dawley rats of both genders in three separate groups for two weeks, and the results of the estriol and vehicle groups, as well as the non-treated control groups, were compared in terms of mechanical tensometric test results and histopathological evaluation. RESULTS: After the application of topical estriol, histologically, subcutis thinned (p<0.01), the thickness of collagen fibrils increased (p<0.01), and elastic fibrils and dermal connective tissue cells appeared denser in female estriol group rats; mechanically, the elasticity modulus increased in the estriol groups of both sexes (p<0.05), whereas breaking strength, tensile strength and strain decreased in female estriol group rats (p<0.05). CONCLUSIONS: Estrogens can change the mechanical and histological features of normal skin, and these changes are observed differently in female and male rats. Further studies to investigate the collagen structure and its interaction with ground substance, as well as effects of estriol on rat skin without a vehicle cream, are necessary to better understand the effects of estriol on skin mechanics.

Animals↗

PubMed1978

A direct radioimmunoassay for estriol-16alpha-glucosiduronate: its use in the determination of plasma and urine levels and renal clearance of this conjugate in pregnancy.

A direct radioimmunoassay which does not require hydrolysis or chromatography has been developed for estriol-16alpha-glucosiduronate in pregnancy plasma and urine. The antigen used in the development of this antiserum was prepared by joining the carboxylic acid group of estriol-16alpha-glucosiduronate covalently to the epsilon-amino group of the lysine residues in bovine serum albumin. Results indicate that the direct radioimmunoassay yields levels of estriol-16alpha-glucosiduronate in late pregnancy urine that are comparable to those obtained by mroe elaborate procedures involving chromatographic separation of the estriol conjugates, followed by enzymic hydrolysis and measurement of the freed estriol. In addition, good correlation was found between the total estrogen values in urine obtained by currently used chemical procedures and urinary levels of estriol-16alpha-glucosiduronate. The renal clearance of estriol-16alpha-glucosiduronate was determined in eight normal women during the third trimester, and the mean value +/- S.D. was 404 +/- 81 ml. per minute (range, 248 to 494). This method is suitable for the evaluation of variations in the plasma and urine levels of estriol-16alpha-glucosiduronate in pregnancy and offers significant advantages over the presently used chemical methods for monitoring fetal well-being.

Animals↗