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PubMed2006

Maternal hormone levels and perinatal characteristics: implications for testicular cancer.

PURPOSE: It was hypothesized that the risk for testicular germ cell tumors (TGCTs) is associated with maternal hormone levels. To examine the hypothesis, some studies used perinatal factors as surrogates for hormone levels. To determine the validity of this assumption, hormone-perinatal factor relationships were examined in the Collaborative Perinatal Project. METHODS: Maternal estradiol, estriol, and testosterone levels in first- and third-trimester serum samples were correlated with perinatal factors in 300 mothers representative of populations at high (white Americans) or low (black Americans) risk for TGCT. RESULTS: For white participants, testosterone levels were associated negatively with maternal height (p < 0.01) and age (p = 0.02) and positively with maternal weight (p = 0.02) and body mass index (BMI; p < 0.01), whereas estradiol levels were associated negatively with height (p = 0.03) and positively with son's birth weight (p = 0.04). For black participants, estriol levels were associated negatively with maternal weight (p = 0.01), BMI (p = 0.02), and gestational age p < 0.01) and positively with son's birth weight (p < 0.01), length (p = 0.04), and head circumference (p = 0.03). CONCLUSIONS: These findings indicate that use of perinatal characteristics as surrogates for hormone levels should be limited to a specific ethnic group. For white men, previously reported associations of TGCT with maternal weight and age may be caused by lower maternal testosterone levels.

Black or African American↗
PubMed2005

Placental defence is considered sufficient to control lipid peroxidation in pregnancy.

Oxidative stress is characterized by an overweight of pro-oxidants against antioxidant forces and is associated with atherosclerosis, aging, and reproductive complications. Placenta is the major source of pro-oxidant agents, antioxidant enzyme-systems, and hormones and is able to keep the lipid peroxidation under control in normal pregnancy. As oxidation processes are increased in pregnancy, we would expect a shortening of lag phase of low density lipoprotein (LDL)-oxidation. LDL oxidation assessed by measuring conjugated diene formation is a marker for the early part of lipid peroxidation process and the balance of pro-oxidants and antioxidants influences length of lag phase. Our results show that resistance of LDL oxidation is unchanged during normal pregnancy in the second and third trimester. Only antioxidants are able to protect LDL. Estriol is an antioxidant, increases the lag-phase of LDL-oxidation in vitro, and its serum concentration raises enormous during late pregnancy. Thus the biological role of high levels of estriol during pregnancy may be part of the self-protection to limit oxidative damages.

Antioxidants↗
PubMed1983

Extra-adrenal deoxycorticosterone production in hypoestrogenic pregnancies: Serum concentrations of progesterone and deoxycorticosterone in anencephalic fetuses and in women pregnant with an anencephalic fetus.

In a continuing effort to define the origin of and the regulation of the production of deoxycorticosterone, we measured deoxycorticosterone and progesterone in the umbilical cord plasma of 16 anencephalic fetuses and newborn infants (21 to 45 weeks' gestation) and deoxycorticosterone, progesterone, 17 beta-estradiol, and estriol in the plasma of 18 women pregnant (16 to 45 weeks) with an anencephalic fetus. Whereas umbilical cord plasma levels of progesterone in the anencephalic fetuses were similar to those of normal abortuses and newborn infants, those of deoxycorticosterone (1.3 +/- 0.21 ng/ml, mean +/- SE) were significantly lower (P less than 0.001) than those in normal abortuses and newborn infants delivered between 31 and 42 weeks' gestation (3.94 +/- 0.26 ng/ml). We found that plasma levels of deoxycorticosterone were significantly correlated (P less than 0.001) to those of progesterone in women pregnant with an anencephalic fetus, as well as in women pregnant with a normal fetus. Plasma levels of deoxycorticosterone (range = 0.14 to 0.92 ng/ml) in women pregnant with an anencephalic fetus were significantly lower than those in women pregnant with a normal fetus; plasma levels of progesterone were similar in both groups. The plasma levels of 17 beta-estradiol and of estriol were extremely low in women pregnant with an anencephalic fetus compared with those in women with a normal fetus and did not vary as a function of gestational age. In one subject who was pregnant with an anencephalic fetus, we found that estrogen treatment (100 mg of diethylstilbestrol/day) for 6 days caused a progressive increase in the serum levels of deoxycorticosterone and in the ratio of the concentration of concentration of deoxycorticosterone to that of progesterone in serum. Both the serum levels of deoxycorticosterone and the ratio of the concentration of deoxycorticosterone and in the ratio of the concentration of deoxycorticosterone to that of progesterone declined after cessation of estrogen treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Glands↗
PubMed1984

The role of nonstress tests, fetal biophysical profile, and contraction stress tests in the outpatient management of insulin-requiring diabetic pregnancies.

Antepartum fetal surveillance methods applicable in a home glucose-monitored population of pregnant diabetic women have been evaluated. A testing sequence of nonstress heart rate testing, backed up by either the fetal biophysical profile or contraction stress testing employed at a twice weekly interval, in 107 outpatients was compared with the management of 140 historic control patients by weekly nonstress tests and daily plasma estriols. There were 617 of 672 (91.8%) reactive nonstress tests in outpatients compared to 566 of 626 (90.4%) reactive tests in hospitalized control patients. Of 13 contraction stress tests performed in the outpatient group, only one was positive. Although 2,670 estriol determinations were done on hospitalized control patients, none was used for outpatients. No losses were attributed to unexplained antenatal stillbirth in either group. A fetal biophysical score of 8 was found to be at least as reliable as a reactive nonstress test. Antenatal surveillance in the well-controlled, insulin-requiring diabetic woman can be safely achieved with a testing sequence that consists of twice weekly nonstress tests backed up by the fetal biophysical profile and contraction stress tests.

Diabetes Mellitus, Type 1↗
PubMed1988

Evidence for a local change in the progesterone/estrogen ratio in human parturition at term.

The purpose of this study was to determine if a local change in the concentrations of estrogen and progesterone occurs in the amniotic fluid during human parturition at term. Amniotic fluid was retrieved from 20 women in active labor and from 20 women not in labor. Patients were matched for maternal age and gestational age. Estradiol, estriol, progesterone, and dehydroepiandrosterone sulfate were measured in amniotic fluid by radioimmunoassay. For women in active labor, the median concentrations (range) of these steroid hormones were 2.4 ng/ml (1 to 9.2 ng/ml), 1661.2 ng/ml (556.6 to 3928.1 ng/ml), 12.3 ng/ml (4.7 to 41.4 ng/ml), and 187.5 ng/ml (61.2 to 470 ng/ml), respectively. The median concentrations (range) for women not in labor were 1.6 ng/ml (0.3 to 5.7 ng/ml), 684.2 ng/ml (70.6 to 2103.1 ng/ml), 13.2 ng/ml (7.5 to 63 ng/ml), and 65.6 ng/ml (20 to 334 ng/ml), respectively. Thus spontaneous human parturition at term was associated with significantly increased amniotic fluid concentrations of estradiol, estriol, and dehydroepiandrosterone sulfate (p = 0.02, p = 0.002, p = 0.003, respectively). The progesterone/estrogen ratios (progesterone/estradiol and progesterone/estriol) were significantly lower for women in active labor compared with those not in labor (p = 0.002 and p = 0.0006, respectively). We conclude that a local change in the progesterone/estrogen ratio occurs during human parturition at term.

Amniotic Fluid↗
PubMed2002

Protection against gp120-induced neurotoxicity by an array of estrogenic steroids.

gp120, the coat protein of HIV, can be neurotoxic and is thought to contribute to AIDS-related dementia complex. Such toxicity involves activation of glutamate receptors, mobilization of free cytosolic calcium, and generation of oxygen radicals. We have previously shown that the estrogen 17beta-estradiol, in concentrations of 100 nM or higher, lessens the neurotoxicity of gp120 in hippocampal and cortical cultures, blunts gp120-induced calcium mobilization, and lessens the oxidative consequences. In this study, we examined the protective potential of other estrogens. We found gp120 neurotoxicity in hippocampal cultures to be significantly lessened by estrone, equilin and estriol, although with an order of magnitude less potent than 17beta-estradiol. We also found all four estrogens to blunt gp120-induced calcium mobilization, with estriol being more efficacious than the other three estrogens. These findings give insight both into the mechanisms of estrogenic protection (e.g. receptor-dependent versus independent actions) as well as into the potential therapeutic use of estrogens against AIDS-related dementia complex.

Animals↗
PubMed1983

Metabolism of 3H-estradiol-17 beta by cultures of isolated rat Sertoli cells and the effect of FSH: presence of 16 alpha-hydroxylase.

The ability of Sertoli cells to metabolize 3H-estradiol-17 beta was investigated utilizing Sertoli cell cultures isolated from 18d rat testes. The Sertoli cells converted estradiol-17 beta to estriol as shown by recrystallization of estriol from samples containing cells and media but not from cell-free control media. The effect of FSH treatment on such metabolism was investigated and was shown to be similar to nontreated samples. This is the first demonstration that 16 alpha-hydroxylase is present in Sertoli cells and that this enzyme activity is not under the influence of FSH.

Animals↗
PubMed1999

Effect of long-term local or systemic hormone replacement therapy on post-menopausal mood disturbances. Influences of socio-economic and personality factors.

OBJECTIVES: To clarify the effect exerted by hormone replacement therapy (HRT) versus socio-economic and personality factors in improving postmenopausal mood disorders. STUDY DESIGN: The effect of the 1-year administration of systemic hormone replacement therapy (HRT; n = 22) or a vaginal cream of estriol (n = 14) versus no treatment (n = 26) was evaluated on mood states of anxiety, depression, somatization and inadequacy, as evaluated by the symptom rating test (SRT) scale. Results were correlated with the woman socio-economic status, and her capability to cope with daytime distresses, as evaluated by the Coping Style questionnaire. RESULTS: A spontaneous decline of all SRT scores, except that of inadequacy, was observed in the group with no treatment. In comparison HRT induced a greater improvement of only the SRT score of inadequacy (P < 0.01) and to a lesser extent of anxiety (P < 0.06). Similarly, vaginal estriol induced a greater decline of the SRT score of inadequacy (P < 0.01). Multiple regression analysis showed that modifications of the total SRT score and the SRT score of anxiety were related mainly to socio-economic factors, while those of the SRT score of depression were related only to the coping style of the woman. The decline of somatization was related only to time since the menopause while, the reduction of the SRT score of inadequacy was only the consequence of therapy, either systemic or local. CONCLUSIONS: In a 1-year period improvement of post-menopausal psychological discomfort, is spontaneous and independent of therapy. Only symptoms of inadequacy are improved by the hormonal therapy. Likely, the perceived menopausal 'losses' make the woman to feel inadequate and the use of sex-related hormones is capable to improve this feeling.

Adaptation, Psychological↗
PubMed1992

Two human liver cDNAs encode UDP-glucuronosyltransferases with 2 log differences in activity toward parallel substrates including hyodeoxycholic acid and certain estrogen derivatives.

Two human liver UDP-glucuronosyltransferase cDNA clones, HLUG25 [Jackson, M. R., et al. (1987) Biochem. J. 242, 581-588] and UDPGTh-2 [Ritter, J. K., et al. (1990) J. Biol. Chem. 266, 7900-7906] have previously been shown to encode isozymes active in the glucuronidation of hyodeoxycholic acid (HDCA) and certain estrogen derivatives (estriols and 3,4-catechol estrogens), respectively. Here we report that the UDPGTh-2-encoded isoform (udpgth-2) and the HLUG25-encoded isoform (udpgth-1) have parallel aglycon specificities. Following expression in COS-1 cells, each isoform metabolized three types of dihydroxy- or trihydroxy-substituted ring structures, including the 3,4-catechol estrogen (4-hydroxyestrone), estriol and 17-epiestriol, and HDCA, but the udpgth-2 isozyme is 100-fold more efficient than udpgth-1. udpgth-1 and udpgth-2 are 86% identical overall (76 differences out of 528 amino acids), including 55 differences in the first 300 amino acids of the amino terminus, a domain which confers isoform substrate specificity. The data indicate that a high level of conservation in the amino terminus is not required for the preservation of substrate selectivity. Analysis of glucuronidation activity encoded by UDPGTh-1/UDPGTh-2 chimeric cDNAs constructed at their common restriction sites, SacI (codon 297), NcoI (codon 385), and HhaI (codon 469), showed that nine amino acids between residues 385 and 469 are important for catalytic efficiency, suggesting that this region represents a domain which is critical for catalysis but distinct from that responsible for aglycon selection.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1998

Plasma renin activity and aldosterone serum concentration are decreased in severe preeclampsia but not in the HELLP-syndrome.

BACKGROUND: To investigate plasma renin activity and aldosterone serum concentrations in severe preeclampsia (PE) or HELLP-syndrome. METHODS: We measured plasma renin activity and serum concentrations of aldosterone, progesterone, estradiol and estriol in 16 patients with PE and 14 patients with HELLP-syndrome and in well-matched normotensive pregnant controls. Additionally, the umbilical venous levels of aldosterone and plasma renin activity were determined in ten corresponding newborns. RESULTS: Serum aldosterone levels as well as plasma renin activity were significantly lower in patients with PE but not in women with HELLP-syndrome when compared to controls. We did not find any relationship either between aldosterone serum concentration or plasma renin activity and progesterone, estradiol or estriol levels in PE or in the HELLP-syndrome. Umbilical venous renin activity and aldosterone levels were higher than in maternal blood, but there were no significant differences in the umbilical venous levels between normotensive pregnancies and pregnancies complicated by either severe PE or HELLP-syndrome. CONCLUSION: It is concluded that in patients with PE well-known changes in the renin-angiotensin-aldosterone system cannot be found in patients with HELLP- syndrome. This finding is not related to alterations in sex steroid levels.

Adult↗
PubMed1999

Enlarged nuchal translucency and low serum protein concentrations as possible markers for Zellweger syndrome.

We present a case of a fetus in which an enlarged nuchal translucency was detected at 12 weeks' gestation. The karyotype was normal. Subsequent ultrasound examination showed no obvious fetal abnormalities apart from a mild pericardial effusion. Serum screening revealed very low concentrations of estriol and human chorionic gonadotropin. After birth the diagnosis of Zellweger syndrome was made. Nuchal translucency screening, estriol level identification and detailed ultrasound scanning may help to identify fetuses affected by this syndrome.

Adult↗
PubMed2001

First-trimester increased nuchal translucency and fetal hypokinesia associated with Zellweger syndrome.

We report the prenatal detection of increased nuchal translucency and decreased fetal movements, at 11 weeks of gestation, in a fetus at risk for Zellweger syndrome. The diagnosis of Zellweger syndrome was confirmed by metabolic studies on cultured chorionic villus sampling (CVS) cells and the pregnancy was terminated. The couple's subsequent pregnancy was monitored using the same method. In this pregnancy the nuchal translucency measured at 12 weeks' gestation was normal, the fetus was active, and biochemical studies using CVS and amniocentesis confirmed normal results. We believe this to be the first reported case of Zellweger syndrome followed prenatally in which an increased nuchal translucency and fetal hypokinesia were detected in the first trimester. During the pregnancy with the affected child the maternal serum screen (MSS) showed low estriol level. We believe this to be the second report of a low estriol level on MSS in a pregnancy affected with Zellweger syndrome.

Adult↗
PubMed1982

Direct influence of the three natural estrogens on human mammary gland in vitro.

The direct influence of the three basic natural estrogens, estrone, 17 beta-estradiol and estriol, on DNA synthesis in human normal mammary epithelial cells was investigated in organ culture during 7 days, and was assessed by autoradiography. A threshold concentration of I.O. ng per ml was needed to elicit a significant stimulation by estradiol and estriol. No significant increase in the incorporation of tritiated-thymidine could be obtained with estrone in the same conditions. These observations are in keeping with the hypothesis put forward by Gurpide, Tseng and Gusberg (1977) that estrone per se might be devoid of any direct estrogenic effect.

Adolescent↗
PubMed1987

A randomized trial of induction at 42 weeks gestation versus expectant management for postdates pregnancies.

A randomized prospective clinical trial of induction of labor at 42 completed weeks gestation versus expectant management in postdates pregnancies was performed. The primary screening test was the 24-hr urinary estriol creatinine ratio. The cesarean section rate was high in both groups and did not differ statistically. Intervention by delivery at 42 weeks decreased the development of small for gestational age infants, but costs slightly more. Twenty-four-hour urinary estriol creatinine ratio determinations predicted fetal distress in labor, but could not predict postmaturity syndrome or infants who were small for gestational age. As expectant management did not differ from induction of labor at 42 weeks from the standpoint of maternal outcome, and as the cost difference was small, induction of labor at 42 weeks may be the preferred management as it improves infant outcome.

Cesarean Section↗
PubMed1992

Prenatal screening for Down's syndrome with use of maternal serum markers.

BACKGROUND: Approximately 35 percent of all cases of Down's syndrome in fetuses can be detected by measuring maternal serum alpha-fetoprotein during the second trimester in the general population of pregnant women. Recent case-control studies indicate that this detection rate could be approximately doubled by measuring serum levels of unconjugated estriol and chorionic gonadotropin, which are abnormally low and abnormally high, respectively, in women carrying fetuses affected by Down's syndrome. METHODS: We prospectively screened 25,207 women and adolescents in the second trimester of pregnancy and assigned each a risk of fetal Down's syndrome with an algorithm that took into account measurements of all three serum markers in combination with maternal age. On this basis, 1661 subjects (6.6 percent) were initially assigned a second-trimester risk of fetal Down's syndrome of at least 1 in 190, and 962 (3.8 percent) were offered amniocentesis for chromosomal analysis after verification of gestational age. Gestational age was determined on the basis of the first day of the last menstrual period or, when available, by ultrasonography. RESULTS: Among the 760 women and adolescents who chose amniocentesis, 20 cases of fetal Down's syndrome were detected, along with 7 other chromosomal disorders. There was 1 additional case of fetal Down's syndrome among the 202 women who chose not to have amniocentesis. The rate of detection of Down's syndrome was thus 58 percent (21 of 36 expected cases), and the frequency of identifying a fetus with Down's syndrome in women undergoing amniocentesis was 1 per 38 amniocenteses (95 percent confidence interval, 1 in 25 to 1 in 62). CONCLUSIONS: Measuring serum alpha-fetoprotein, chorionic gonadotropin, and estriol is more effective in screening for fetal Down's syndrome than measuring maternal serum alpha-fetoprotein alone. Such an expanded protocol can readily be incorporated into existing prenatal screening programs.

Adolescent↗
PubMed1998

Screening of maternal serum for fetal Down's syndrome in the first trimester.

BACKGROUND: Screening of maternal serum to identify fetuses with Down's syndrome is now routinely offered during the second trimester of pregnancy. Prenatal screening by means of serum assays or ultrasonographic measurements, either alone or in combination, may also be possible in the first trimester. METHODS: We measured serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin (hCG), the free beta subunit of hCG, and pregnancy-associated protein A in 4412 women (82 percent of whom were 35 years of age or older) who came to 16 prenatal diagnostic centers for chorionic-villus sampling or early amniocentesis at 9 to 15 weeks of gestation. Ultrasound measurements of fetal nuchal translucency were also reported. Fetal chromosomal analysis was performed in all pregnancies. Altogether, there were 61 fetuses with Down's syndrome. RESULTS: A total of 48 pregnancies affected by Down's syndrome and 3169 unaffected pregnancies were identified before 14 weeks of gestation; the rates of detection of Down's syndrome for the five serum markers were as follows: 17 percent for alpha-fetoprotein, 4 percent for unconjugated estriol, 29 percent for hCG, 25 percent for the free beta subunit of hCG, and 42 percent for pregnancy-associated protein A, at false positive rates of 5 percent. The results of the measurements of serum hCG and its free beta subunit were highly correlated. When used in combination with the serum concentration of pregnancy-associated protein A and maternal age, the detection rate was 63 percent for hCG (95 percent confidence interval, 47 to 76 percent) and 60 percent for its free beta subunit (95 percent confidence interval, 45 to 74 percent). Measurements of nuchal translucency varied considerably between centers and could not be reliably incorporated into our calculations. CONCLUSIONS: Screening for Down's syndrome in the first trimester is feasible, with use of measurements of pregnancy-associated protein A and either hCG or its free beta subunit in maternal serum.

Adolescent↗
PubMed1999

Integrated screening for Down's syndrome based on tests performed during the first and second trimesters.

BACKGROUND: Both first-trimester screening and second-trimester screening for Down's syndrome are effective means of selecting women for chorionic-villus sampling or amniocentesis, but there is uncertainty about which screening method should be used in practice. We propose a new screening method in which measurements obtained during both trimesters are integrated to provide a single estimate of a woman's risk of having a pregnancy affected by Down's syndrome. METHODS: We used data from published studies of various screening methods employed during the first and second trimesters. The first-trimester screening consisted of measurement of serum pregnancy-associated plasma protein A in 77 pregnancies affected by Down's syndrome and 383 unaffected pregnancies and measurements of nuchal translucency obtained by ultrasonography in 326 affected and 95,476 unaffected pregnancies. The second-trimester tests were various combinations of measurements of serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin A in 77 affected and 385 unaffected pregnancies. RESULTS: When we used a risk of 1 in 120 or greater as the cutoff to define a positive result on the integrated screening test, the rate of detection of Down's syndrome was 85 percent, with a false positive rate of 0.9 percent. To achieve the same rate of detection, current screening tests would have higher false positive rates (5 to 22 percent). If the integrated test were to replace the triple test (measurements of serum alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin), currently used with a 5 percent false positive rate, for screening during the second trimester, the detection rate would be higher 85 percent vs. 69 percent), with a reduction of four fifths in the number of invasive diagnostic procedures and consequent losses of normal fetuses. CONCLUSIONS: The integrated test detects more cases of Down's syndrome with a much lower false positive rate than the best currently available test.

Adolescent↗
PubMed2000

Corticotropin-releasing hormone, corticotropin-releasing hormone-binding protein, and activin A in maternal serum: prediction of preterm delivery and response to glucocorticoids in women with symptoms of preterm labor.

OBJECTIVE: The aim of this study was to determine prospectively whether serum concentrations of corticotropin-releasing hormone, corticotropin-releasing hormone-binding protein, and activin A (1) predict preterm birth within 10 days of hospital admission or at <37 weeks' gestation among women with symptoms of preterm labor and (2) are affected by glucocorticoid therapy. STUDY DESIGN: Serum concentrations of corticotropin-releasing hormone and activin A were measured in 94 women with symptoms of preterm labor between 24 and 34 weeks' gestation, and delivery outcomes were monitored. Corticotropin-releasing hormone-binding protein concentrations were measured in 71 of these women. In a subgroup of 15 women the serum analytes were assayed in conjunction with estriol before and 12 to 24 hours after administration of dexamethasone. RESULTS: Forty-six percent (6/13) of the women who were delivered within 10 days of hospital admission had a raised serum corticotropin-releasing hormone level, but the predictive relationship was not significant (chi(2) = 1.7; P =.2). Among the 31 women (including the 6 previously mentioned) who were delivered at <37 weeks' gestation, 39% (12/31) had a raised corticotropin-releasing hormone level. Although a raised corticotropin-releasing hormone concentration was positively associated with delivery at <37 weeks' gestation (chi(2) = 9; P =.003), the predictive diagnostic value was poor, with sensitivity, specificity, and positive and negative predictive values of 39%, 90%, 67%, and 75%, respectively. The serum concentrations of corticotropin-releasing hormone-binding protein and activin A were unrelated to gestational age at delivery. Dexamethasone markedly lowered the serum estriol level (P <.001) but had no effect on concentrations of corticotropinreleasing hormone, corticotropin-releasing hormone-binding protein, and activin A. CONCLUSION: Serum concentrations of corticotropin-releasing hormone, corticotropin-releasing hormone-binding protein, and activin A are not clinically useful for the prediction of preterm delivery among women with symptoms of preterm labor and are not affected by administration of glucocorticoids.

Activins↗