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PubMed1993

An association between elevated levels of human chorionic gonadotropin in the midtrimester and adverse pregnancy outcome.

OBJECTIVE: Unexplained elevations in maternal serum alpha-fetoprotein in the midtrimester are associated with adverse pregnancy outcome. Recently it has also been suggested that elevations of maternal serum human chorionic gonadotropin in the second trimester may be associated with adverse pregnancy outcome. STUDY DESIGN: We conducted a cohort study of 460 women at Swedish Medical Center, Seattle, Washington, between Jan. 1, 1990, and Aug. 15, 1991, inclusive. Entry criteria for the cohort included (1) triple screen analysis (maternal serum alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol) between 15 and 18 weeks' gestation, (2) a risk for Down syndrome of more than one in 195 on the basis of triple screen analysis, (3) study group human chorionic gonadotropin > or = 2 multiples of the median and referent group < or = 2 multiples of the median, alpha-fetoprotein < or = 2 multiples of the median, unconjugated estriol > or = 0.5 multiples of the median, and (4) chromosomally normal single gestation without anomalies. Cumulative incidence risk ratios were estimated for each pregnancy outcome as a measure of the relative association with elevated human chorionic gonadotropin (> or = 2.0 multiples of the median) and adverse pregnancy outcome: low birth weight, < or = 2500 gm; preterm delivery, < 37 weeks' gestation; and small for gestational age, < or = 10th percentile. The Mantel extension test was used to evaluate any apparent linear trend in risk between level of human chorionic gonadotropin and adverse pregnancy outcome. RESULTS: Elevated human chorionic gonadotropin levels were associated with an increased risk for low birth weight (relative risk = 4.0), preterm delivery (relative risk = 2.8), and small for gestational age (relative risk = 1.8). The risk for each adverse outcome increased with increasing levels of human chorionic gonadotropin. CONCLUSIONS: Elevations of human chorionic gonadotropin in the midtrimester appear to be associated with adverse pregnancy outcome. The magnitude of the risk correlates with the level of human chorionic gonadotropin. This risk appears to be independent of the risk for adverse pregnancy outcome associated with unexplained elevations of maternal serum alpha-fetoprotein.

Chorionic Gonadotropin↗
PubMed1987

4'-[Aminomethyl]fluorescein and its N-alkyl derivatives: useful reagents in immunodiagnostic techniques.

A new class of fluorescein derivatives with chemically reactive amino and N-alkylamino "arms" in the 4'-position were synthesized and their utility in the development of fluorescence polarization immunoassays (FPIA) for cortisol and estriol was evaluated. The positioning of the arm in one of the phenolic rings introduced chirality due to hindered rotation and led to rotational isomers. These were separable when brought into a chiral environment, i.e., conjugated to steroid molecules. In the case of cortisol conjugates, the rotamers had similar properties in the FPIA. In the case of estriol conjugates, however, each rotamer exhibited different immunoassay characteristics. The rotamers interconverted at 80 degrees C, with the rate increasing with temperature. An unusual N-alkylation phenomenon by alkanols in acidic medium was observed. A serum cortisol FPIA, developed using an N-alkylamino fluorescein derivative, showed good correlation with a reference RIA.

Alkylation↗
PubMed1994

The permeability of the human red cell membrane to steroid sex hormones.

The release rates of the 3H-labeled steroid sex hormones estrone, estradiol, estriol, progesterone, and testosterone from the human red blood cell and resealed red cell ghosts were studied at 38 degrees C and pH 7.2 by means of the rapid continuous flow tube method which has a time resolution of a few milliseconds. Further, the equilibria between unbound hormone and hormone bound to red cells, resealed red cell ghosts and albumin were studied by partitioning analysis of trace amounts of labeled hormones. The half-times for release from erythrocytes under physiological conditions ranged from 4 ms (testosterone) to 150 ms (estriol). The release from ghosts was significantly faster than from cells preincubated with hormones at unphysiological high concentrations. Affinities of hormone binding to cells and hormone indicate that as much as 15-35% of the total hormone content in whole blood is confined to red cells. The ratio between bound and free hormone in the cell ranged from 5 to 10, and the ratio between cytoplasma-bound and membrane-bound hormone ranged between 3 and 9. The results are compatible with a model of fast transition of hormone through the red cell membrane and intracellular binding of hormone. We suggest that red cells function as carriers of sex hormones in the bloodstream in a manner similar to that of albumin, and that red cells may be responsible for 5-15% of sex hormone delivery to target tissues.

Binding Sites↗
PubMed1980

Nuclear translocation of estrogen-receptor complex and stimulation of RNA synthesis by estrogens of different biological potencies in the female rat pituitary.

Stimulation of RNA synthesis and of nuclear translocation of estrogen-receptor complexes was investigated in isolated nuclei of anterior pituitaries of castrated female rats after injection with estrogens of different biological potencies. The assay system for the estimation of total RNA synthesis was validated and data suggest that incorporation of [3H]UMP into acid-precipitable material is consistent with RNA synthesis. An increase in RNA synthesis was seen 30 min after application of either 17 beta-estradiol, estriol or 1,3-diacetyl-17 alpha-ethinyl-7 alpha-methyl-1,3,5,(10)estratriene-17,3-ol (DMEE). RNA synthesis was maximal 90 min after estrogen application. Thereafter, RNA synthesis decreased slowly and reached pretreatment levels 3, 8 and 30 h after application of estriol, 17 beta-estradiol and the diacetyl derivative of ethinyl-estradiol, respectively. All estrogens were found to stimulate rapidly nuclear translocation of estrogen-receptor complexes. Peak levels of nuclear receptor contents were reached 30 min after administration of estrogens. A concomitant depletion of cytosol receptor levels was noted. Nuclear retention of estrogen-receptor complexes paralelled duration of enhanced RNA synthesis and correlated with biological potencies of the steroids. Data of present experiments combine to suggest that long-term nuclear retention is a requisite for expression of biological activity of estrogens at the anterior pituitary. Furthermore, the degree of biological activity seems to be associated with duration of stimulation of RNA synthesis, amount of estrogen-receptor complexes translocated to the nucleus, and duration of nuclear retention.

Animals↗
PubMed1978

Performance of various mathematical methods for computer-aided processing of radioimmunoassay results.

Interpolation and regression methods are available for computer aided determination of radioimmunological end results. We compared the performance of 6 algorithms (weighted and unweighted linear logit log regression; quadratic logit log regression, smoothing spline interpolation with a large and small smoothing factor, respectively, and polygonal interpolation and the manual curve fitting on the basis of three radioimmunoassays with different reference curve characteristics (digoxin, estriol, human chorionic somatomammotrophin (HCS)). Great store was set by the accuracy of the approximation at the intermediate points on the curve, i.e. those points that lie midway between two standard concentrations. These concentrations were obtained by weighing and inserted as unknown samples. In the case of digoxin and estriol the polygonal interpolation provided the best results, while the weighted logit log regression proved superior in the case of HCS.

Computers↗
PubMed1987

In vitro metabolism of androstenedione and identification of endogenous steroids in Helix aspersa.

In vitro metabolism of androstenedione in gonads of juvenile and adult Helix aspersa has been investigated. The conversion of [3H]androstenedione into testosterone, 5 alpha-dihydrotestosterone, androsterone, and estriol was demonstrated. In juvenile animals testosterone (59.8%) is the major metabolite whereas in adult animals androsterone (18.8%) is. The following endogenous steroids have been identified by gas chromatography-mass spectrometry in adult gonads: androsterone, dehydroepiandrosterone, androstenedione, 3 alpha-androstanediol, estrone, estradiol-17 beta, and estriol. The levels of testosterone, 5 alpha-dihydrotestosterone, androstenedione, and progesterone have been measured by RIAs in gonads and hemolymph. Their levels vary with the physiological stage: the gonadal and circulating levels of testosterone decrease with the sexual maturation whereas the 5 alpha-dihydrotestosterone increases. These differences observed in metabolism and in level of steroids between the juvenile and the adult snails allow us to suppose that these steroids have a biological role.

Androstenedione↗
PubMed1983

Fetal sex dependent hormone levels in early pregnant women with elevated maternal serum alpha-fetoprotein.

Maternal serum and amniotic hormone levels have been investigated in two groups of women in pregnancy weeks 18-21. One group (B) was composed of women with high alpha-fetoprotein levels in serum without fetal abnormality, and a matched control group (A) with normal alpha-fetoprotein levels in serum. Amongst group B women were four pregnancy complications: two spontaneous abortions, one premature delivery, and one cesarean section due to fetal asphyxia. Group B women were significantly different from group A women. Thus, higher maternal serum levels of total estriol (P = 0.030), testosterone (P = 0.016), and alpha-fetoprotein (P = 0.018) were noted in the presence of male fetuses; and higher hPL (P = 0.004), FSH (P = 0.037), and alpha-fetoprotein (P = 0.002) concentrations in women carrying female fetuses, who were accompanied by lower total estriol concentrations (P = 0.045). Differences between groups B and A in terms of amniotic fluid analyses were only related to female fetal sex. Thus, group B showed higher hPL (P = 0.028), testosterone (P = 0.020), and FSH (P = 0.006) levels, and lower alpha-fetoprotein (P = 0.013) concentrations. It is concluded that elevated maternal serum levels of alpha-fetoprotein are accompanied in female fetuses by an endocrine milieu different from that of matched controls. This difference may put the conceptus at a disadvantage, but the majority of the girls were born on time without signs of small-for-date.

Adult↗
PubMed1984

Characterization of the interaction between estrogen metabolites and taurocholate for uptake into isolated hepatocytes. Lack of correlation between cholestasis and inhibition of taurocholate uptake.

The cholestasis induced by estrogen metabolites has been postulated to be due to an inhibition of bile acid transport. Therefore, the uptake of [3H]taurocholate (TC) into isolated hepatocytes was examined in the presence of known cholestatic steroid glucuronides. The cholestatic D-ring glucuronide conjugates of estradiol, estriol, ethynylestradiol and dihydrotestosterone did not inhibit the uptake of TC suggesting that these organic anions are transported by different carrier systems. Estrone sulfate inhibited TC uptake 65% but did not decrease bile flow following i.v. administration to the rat (22 mumol/kg), under conditions which the steroid glucuronide estradiol-17 beta-(beta-D-glucuronide) ( E217G ) decreased bile flow 100%. The hepatocytic uptake of [3H] E217G (100 microM) was inhibited by estriol-16 alpha-(beta-D-glucuronide) (200 microM, 40%) and estradiol-17 beta-3-(beta-D-glucuronide) (200 microM, 22%) as well as by the organic anions bromosulfophthalein (150 microM, 57%), dibromosulfophthalein (150 microM, 59%), indocyanine green (150 microM, 62%), rose bengal (150 microM, 56%) and bilirubin (50 microM, 40%). Thus, the bile acids and steroid glucuronides are transported into the hepatocyte by different carrier systems so that the cholestasis induced by the steroid D-ring glucuronides cannot be explained by an inhibition of bile acid uptake. Furthermore, the hepatocytic uptake of E217G occurs by a carrier system similar to that for the other steroid glucuronides and organic anions.

Animals↗
PubMed1980

Hormone patterns during bromocriptine-induced pregnancy in hyperprolactinemic patients.

Plasma prolactin (PRL) and human placental lactogen (HPL), and urinary estriol and pregnanediol were studied during pregnancies induced with bromocriptine (Parlodel, Sandoz) in 10 cases of hyperprolactinemia. Previous selective adenomectomy or intrasellar implantation of radioactive gold (198Au) failed to induce a complete remission in 3 of these subjects. PRL rapidly increases after bromocriptine withdrawal, reaching values higher than those in normal women in the same stage of pregnancy within a few weeks. At term, pathological PRL levels occurred in 3 subjects only (with distinct alterations of the sella turcica). Estriol, pregnanediol and HPL were normal in all cases. These findings suggest that PRL levels higher than those normally observed during pregnancy do not alter fetoplacental endocrine function.

Adult↗
PubMed1987

The efficacy of biochemical assays in assessing an IUGR risk-group, preselected with ultrasound fetometry.

Dehydroepiandrosterone sulphate, progesterone, estradiol, estriol and human placental lactogen (hPL) were biochemically assayed in a group of 92 pregnancies in which intra-uterine growth retardation was suspected. The group was selected with ultrasound fetometry at 32 weeks of gestation, and maternal blood was sampled at 33, 35, 37 and 39 weeks of gestation. The IUGR group consisted of 30 pregnancies resulting in the birth of an infant with a birthweight of 2 standard deviations or more below the mean for gestational age in the Malmö population. Intra-uterine growth trends were defined by serial ultrasound fetometry performed every second week. Both serum hormone and hPL content were examined in relation to birth-weight, occurrence of imminent asphyxia at delivery, Apgar score, and pH in the umbilical vein. Neither dehydroepiandrosterone sulphate, nor progesterone nor estradiol values correlated to any of the outcome variables. To some extent estriol values distinguished IUGR from non-IUGR fetuses but not until the 39th gestational week, whereas hPL was effective in this respect in all weeks studied. An hPL value below 4 mg/l predicted IUGR with a sensitivity ranging from 52% to 74%, and a specificity ranging from 85% to 78%. HPL correlated well with the subsequent intra-uterine growth rate, but not with the outcome variables studied.

Adult↗
PubMed1992

Responses of placental steroids, prostacyclin and thromboxane A2 to thermal stress during pregnancy.

The effect of heat stress on plasma prostacyclin and thromboxane A2 and serum estradiol, estriol and progesterone responses was studied in pregnant and non-pregnant women. Group I consisted of 15 healthy non-pregnant women, group II of 23 women 13-14 weeks pregnant, and group III of 23 women 36-37 weeks pregnant. Blood samples were taken before the heat stress, at the end of the stress (70 degrees C for 20 min) and 20 min and/or 45 min after the end of stress. The rectal temperature increased 0.3-0.4 degrees C. The concentration of progesterone did not change during the experiment but that of estradiol increased by 11% (P less than 0.005) in group II and by 10% (P less than 0.01) in group III after the end of the stress. Estriol increased only in group III (by 12%, P less than 0.005) after the end of the stress and the increase was higher as compared to group II (P less than 0.005). The metabolite of prostacyclin increased only in group III by 15% (P less than 0.05) during the heat stress. The metabolite of thromboxane A2 decreased in group II by 20% (P less than 0.005) at the end of the stress while there was no change in group III. The fetal heart rate reactivity remained unchanged and only few uterine contractions were recorded. The small changes found in the levels of prostanoids and placental steroids in response to heat stress do not seem to have any deleterious effects on fetal well-being. The slightly increased concentration of placental steroids may rather reflect changes in metabolism than an increase in uteroplacental blood flow.

6-Ketoprostaglandin F1 alpha↗
PubMed1975

New approach to the study of hormone-protein interaction using the microcalorimetric method.

Binding enthalpies of various hormones to bovine serum albumin (BSA) and human serum albumin (HSA) in 50 mM phosphate buffer, pH 7.4, at 37 degrees C have been determined by direct microcalorimetry. The observed enthalpies of binding of progesterone, testosterone, dihydrotestosterone, corticosterone and estriol to BSA were found to be -13.24 plus or minus 0.11 -10.31 plus or minus 0.02, -2.37 plus or minus 0.46, -17.64 plus or minus 0.32 and -17.14 plus or minus 0.36 kcal/mol of hormone, respectively. under the same experimental conditions the enthalpies of binding of progesterone, testosterone, dihydrotestosterone, corticosterone and estriol to HSA were found to be -23.94 plus or minus 0.32, -18.88 plus or minus 0.49, -11.14 plus or minus 0.02, -9.88 plus or minus 0.14 and -20.85 plus or minus 0.39 kcal/mol of hormone, respectively.

Animals↗
PubMed1978

Direct radioimmunoassay of specific urinary estrogen glucosiduronates in normal men and nonpregnant women.

Direct radioimmunoassay are described for the measurement of each of three specific estrogen glucosiduronates: estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate and estriol-16 alpha-glucosiduronate in urine. Each assay utilizes a specific antiserum prepared by complexing the carboxylic acid group of the appropriate glucosiduronate to the epsilon-amino group of lysine in bovine serum albumin or bovine thyroglobulin. The antisera showed little or no cross reactivity toward other estrogens that might be present in significant amounts in urine. These antisera were used for the direct assay of the conjugates in urine from normal men and nonpregnant women without prior extraction or chromatography. The values were similar to those obtained after extraction, chromatographic purification on DEAE-Sephadex and subsequent immunoassay; The following mean values +/- SE (microgram/g creatinine) were obtained: estrone glucosiduronate, male 10.1 +/- 0.6, follicular phase female 17.3+/- 1.6, luteal phase female 31.8 +/- 2.5; 17 beta-estradiol-17-glucosiduronate, male 1.7 +/- 0.3, follicular phase female 2.4 +/- 0.1, luteal phase female 4.2 +/- 0.4; estriol-16 alpha-glucosiduronate, male 1.8 +/- 0.2, follicular phase female 4.7 +/- 0.9, luteal phase female 10.0 +/- 1.6.

Antibody Specificity↗
PubMed1986

Estrogen regulation of tissue plasminogen activator in a human melanoma cell line.

The influence of ethinylestradiol and the three natural estrogens, i.e. estrone, 17-beta-estradiol and estriol, was studied in a melanoma cell line producing a tissue-type plasminogen activator (t-PA). The cell cultures were exposed to the four estrogens by addition of the steroids dissolved in a weak alcoholic solution to the culture media, in which the released t-PA was assayed by an immunoradiometric method. Ethanol (0.76% w/v) stimulated the t-PA production, while no significant effect of the estrogens in the concentration of 1.7 X 10(-7) M was seen. By tenfold increase in estrogen concentration a highly significant reduction of t-PA levels was recorded in the cultures exposed to ethinylestradiol and 17-beta-estradiol. Estriol differed from these two estrogens in having rather weak inhibitory effect; whereas estrone in this concentration had toxic effect on melanoma cells. It was concluded that the present estrogens, in particular ethinylestradiol and 17-beta-estradiol, had a dose-dependent inhibitory effect on the production of t-PA in melanoma cell culture.

Cell Line↗
PubMed1994

Treatment of skin ageing symptoms in perimenopausal females with estrogen compounds. A pilot study.

A wide range of somatic symptoms of the perimenopausal female is due to the decrease of estrogen at that age. Minor attention has been paid hitherto to the involvement of estrogens in female skin ageing symptoms. In our study, the ageing skin of the face of perimenopausal females was treated with a 0.3% estriol cream (8 patients) or with a 0.01% estradiol cream (10 patients) for 6 months. Dermatologic follow-up was performed monthly. At each follow-up venous blood for radioimmuno assay determination of prolactin (PRL), follicle stimulating hormone (FSH) and estradiol (E2) was sampled. In addition, prior to and after 3 and 6 months of treatment, gynecological examinations for climacteric symptoms, mammary and colposcopic investigations and vaginal smears for cytology were performed. Both treatment groups showed improvement of the various skin ageing symptoms at the end of treatment. The effects of the group treated with topical estriol were slightly superior with regard to their extent and onset. No hormonal side effects were noted either clinically or by hormone monitoring. According to these preliminary results, local estrogen treatment appears to be a promising new approach for the treatment of skin ageing in perimenopausal females. However, for minimizing the risk of systemic hormonal side effects, concentrations and size of application field should be limited.

Administration, Cutaneous↗
PubMed1989

Influences of estradiol and of catechol and non-catechol estrogens on the output of prostaglandins in uteri from spayed rats.

The effects of 17-beta estradiol and of some catechol and non-catechol-estrogens on the synthesis and output of prostaglandins (PGs) E and F by uteri from ovariectomized rats, were explored. Uteri from castrated animals released twice as much PGE than PGF. When uterine tissue was obtained from spayed rats injected prior to sacrifice with a low dose of 17-beta estradiol (0.5 + 1.0 microgram, on two consecutive days), the output of PGE diminished significantly. With a higher dose of the hormone (0.5 + 50.0 micrograms) the depressive influence on the synthesis and release of PGE was even more marked, whereas the output of PGF rose significantly. Low or high doses of estrone or of estriol failed to affect the release of either one of the PGs determined. On the other hand, 2-0H-estradiol at a low dose had no action but at a higher one inhibited the release of PGE without influencing PGF. Neither low nor high doses of 2-0H estriol or of 2-0H estrone affected the synthesis and release of uterine PGs. It was also observed that all the compounds tested evoked a significant uterotrophic action. It appears plausible that some catechol metabolites of 17-beta estradiol, but not other catechol-estrogens, could be involved in the mechanism of action of 17-beta estradiol modulating the production of PGs by the rat uterus.

Animals↗
PubMed1995

Estrogen metabolism in microsomal, cell, and tissue preparations of kidney and liver from Syrian hamsters.

The estrogen-treated golden Syrian hamster has been used as an experimental model for estrogen-induced and estrogen-dependent cancers, but pathways to neoplastic transformation remain unknown in this animal. Metabolism of estrogens to activated or reactive compounds, followed by subsequent oxidative damage to the target tissue, remains a potential step in the tumorigenic process. In this study, the extent of estrogen metabolism is compared in three different in vitro preparations from untreated and estrogen-treated Syrian hamsters, primary kidney cell cultures, microsomal preparations, and freshly prepared tissue kidney slices. In primary kidney cell cultures, the amount of catechol estrogens decreased upon increasing estrogen (DES) treatment period, and completely disappeared after about 6 months treatment. This decrease is not a result of formation of less amounts of catechol estrogens, but rather reflects the presence of the enzyme systems to further metabolize any formed catechol estrogens, since the amount of catechol estrogens formed, as detected by 3H2O release, is unchanged. The polar metabolites a, b and c increased with estrogen treatment, and metabolite c appeared only after DES treatment. The appearance of polar metabolite c only in kidney preparations from DES-treated animals implies that it may serve as a marker of cellular transformation. Estriol and estrone were detected, but were not affected by DES treatment, while no methoxyestrogens were isolated. Studies of estradiol metabolism in microsomal preparations showed a very low rate of metabolism, compared to the primary kidney cell cultures. In contrast, estrogen metabolism was extensive in kidney slices from untreated hamsters, with only approx. 30% of the substrate estradiol remaining unmetabolized after 6 h of incubation. While no catechol estrogens were detected, a small quantity of estriol, and a large amount of estrone and methoxyestrogens were isolated. The polar metabolite a was the main polar metabolite detected, with very little of metabolite b and no metabolite c. In kidney slices from 4 month DES-treated hamsters, a much higher amount of polar metabolites was detected, and metabolite c appeared after 6 h incubation. Mass spectrometric analysis and HPLC data of metabolite c indicate that this metabolite is 15 alpha-hydroxyesteradiol. This metabolite may serve as a biomarker for changes occurring in the hamster kidney cells under continuous estrogen exposure. Finally, formation of water soluble conjugates was demonstrated in both kidney slices and liver slices from Syrian hamsters, with glucuronide, sulfate and thioether conjugates of estrone and estradiol and glucuronides of catechol estrogens detected.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2004

The impact of protease inhibitors on maternal serum screening analyte levels in pregnant women who are HIV positive.

OBJECTIVE: The purpose of this study was to compare alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol levels in women who take protease inhibitors and those women who do not. STUDY DESIGN: This retrospective review from August 2000 to May 2003 was performed for maternal serum screen results, medication use, pregnancy, and perinatal outcomes. RESULTS: Thirty-nine women met study criteria. Sixteen women were treated with protease inhibitors, and 23 women were not treated with protease inhibitors. There was no difference in initial viral load or initial CD4 count between the groups. No difference was found for human chorionic gonadotropin and estriol levels; significantly lower alpha-fetoprotein multiples of the median were found for the women who were treated with protease inhibitors compared with the women who were not (0.97 +/- 0.32 [SD] MoM vs 1.2 +/- 0.4 MoM, respectively; P = .04). Six of 39 women (15%) had positive maternal serum screens. All the babies were normal at birth, and there were no cases of perinatal transmission of human immunodeficiency virus. CONCLUSION: Protease inhibitors are associated with lower alpha-fetoprotein levels in women who are infected with human immunodeficiency virus.

Adult↗