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E2
Kinds of E2 Terms modified by E2 Selected AbstractsEffects of short-term food deprivation on orexin-A-induced intestinal bicarbonate secretion in comparison with related secretagoguesACTA PHYSIOLOGICA, Issue 3 2010G. Flemström Abstract Studies of gastrointestinal physiology in humans and intact animals are usually conducted after overnight fast. We compared the effects of orexin-A, vasoactive intestinal polypeptide (VIP), melatonin, serotonin, uroguanylin, ghrelin and prostaglandin E2 (PGE2) on duodenal bicarbonate secretion in fed and overnight fasted animals. This review is a summary of our findings. Secretagogues were administered by intra-arterial infusion or luminally (PGE2). Enterocyte intracellular calcium ([Ca2+]i) signalling was studied by fluorescence imaging. Total RNA was extracted, reverse transcripted to cDNA and expression of orexin receptors measured by quantitative real-time PCR. Orexin-A stimulates the duodenal secretion in continuously fed animals but not in food-deprived animals. Similarly, short-term fasting causes a 100-fold decrease in the amount of the muscarinic agonist bethanechol required for stimulation of secretion. In contrast, fasting does not affect secretory responses to intra-arterial VIP, melatonin, serotonin, uroguanylin and ghrelin, or that to luminal PGE2. Orexin-A induces [Ca2+]i signalling in enterocytes from fed rats but no significant [Ca2+]i responses occur in enterocytes from fasted animals. In addition, overnight fasting decreases the expression of mucosal orexin receptors. Short-term food deprivation thus decreases duodenal expression of orexin receptors and abolishes the secretory response to orexin-A as well as orexin-A-induced [Ca2+]i signalling. Fasting, furthermore, decreases mucosal sensitivity to bethanechol. The absence of declines in secretory responses to other secretagogues tested strongly suggests that short-term fasting does not affect the secretory capacity of the duodenal mucosa in general. Studies of intestinal secretion require particular evaluation with respect to feeding status. [source] Growth and optical characterization of Cd1- xBexSe and Cd1- xMgxSe crystalsCRYSTAL RESEARCH AND TECHNOLOGY, Issue 4-5 2005F. Firszt Abstract Cd1- xBexSe and Cd1- xMgxSe solid solutions were grown from the melt by the high pressure Bridgman method. Optical, luminescence and photothermal properties of these materials were investigated. Spectroscopic ellipsometry was applied for determination of the spectral dependence of the complex dielectric function (E) and refractive index n(E) at room temperature in the photon energy range 0.75-6.5 eV for samples with optic axis (c-axis) perpendicular to the air-sample interface. The critical point (CP) parameters for E0 and E1 transitions were determined using a standard excitonic CP function to fit the numerically calculated differential spectra ,2,2/,E2. The dispersion of the refractive index of the alloys was modelled using a Sellmeier-type relation. The values of fundamental and exciton band-gap energies were estimated from the ellipsometric and photoluminescence measurements. The origin of luminescence in Cd1- xBexSe and Cd1- xMgxSe was discussed. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Influence of hormones and hormone metabolites on the growth of schwann cells derived from embryonic stem cells and on tumor cell lines expressing variable levels of neurofibromin,DEVELOPMENTAL DYNAMICS, Issue 2 2008Therese M. Roth Abstract Loss of neurofibromin, the protein product of the tumor suppressor gene neurofibromatosis type 1 (NF1), is associated with neurofibromas, composed largely of Schwann cells. The number and size of neurofibromas in NF1 patients have been shown to increase during pregnancy. A mouse embryonic stem cell (mESC) model was used, in which mESCs with varying levels of neurofibromin were differentiated into Schwann-like cells. NF1 cell lines derived from a malignant and a benign human tumor were used to study proliferation in response to hormones. Estrogen and androgen receptors were not expressed or expressed at very low levels in the NF1+/+ cells, at low levels in NF1+/,cells, and robust levels in NF1,/,cells. A 17,-estradiol (E2) metabolite, 2-methoxy estradiol (2ME2) is cytotoxic to the NF1,/, malignant tumor cell line, and inhibits proliferation in the other cell lines. 2ME2 or its derivatives could provide new treatment avenues for NF1 hormone-sensitive tumors at times of greatet hormonal influence. Developmental Dynamics 237:513,524, 2008. © 2008 Wiley-Liss, Inc. [source] Identification of prostaglandin E2 receptors mediating perinatal masculinization of adult sex behavior and neuroanatomical correlatesDEVELOPMENTAL NEUROBIOLOGY, Issue 12 2008Christopher L. Wright Abstract Prostaglandin E2 (PGE2) mediates the organization of male rat sexual behavior and medial preoptic area (MPOA) neuroanatomy during a sensitive perinatal window. PGE2 is up-regulated in response to estradiol, and initiates a two-fold increase in dendritic spines densities on neurons. All the four receptors for PGE2 and EP1-4 are present in developing POA, a critical region controlling male sexual behavior. Previous studies explored that EP receptors are involved in PGE2-induction of neonatal levels of spinophilin protein, a surrogate marker for dendritic spine formation, but did not assess behavioral masculinization. Here, we used two approaches, suppression of EP receptor expression with antisense oligonucleotides and activation of EP receptors with selective agonists, to test which receptors are necessary and sufficient, respectively, for the effects of PGE2 on behavior and neuronal morphology. In female rats, neonatal treatment with antisense oligonucleotides against EP2 or EP4 but not EP1 or EP3 completely prevented the expression of adult behavior organized by PGE2 exposure. The effects of ONO-DI-004, ONO-AE-259-01, ONO-AE-248, and ONO-AE1-329 (EP1-4 agonists respectively) were equivalent to PGE2 treatment, which suggests activating any EP receptor neonatally suffices in masculinizing sex behavior. When given alone, not all EP agonists increased neonatal POA spinophilin levels; yet giving each agonist neonatally increased adult levels. Moreover, adult spinophilin levels significantly correlated with two measures of male sexual behavior. The body of evidence suggests that EP2 and EP4 are both necessary and sufficient for PGE2-induced masculinization of sex behavior, whereas EP1 and EP3 provide redundant roles. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source] Monetary Policy, Credit and Aggregate Supply: The Evidence from ItalyECONOMIC NOTES, Issue 3 2002Riccardo Fiorentini This paper concerns theory and evidence of the monetary transmission mechanisms. Current research has deeply investigated factors, such as dependence of firms on bank credit, that amplify the impact of monetary policy impulses on aggregate demand exerting strong but temporary effects on output and employment. We present an intertemporal macroeconomic equilibrium model of a competitive economy where current production is financed by bank credit, and then we use it to identify supply,side effects of the credit transmission mechanism in data drawn from the Italian economy. We find evidence that the ,credit variables' identified by the model , the overnight rate as a proxy of monetary policy and a measure of credit risk , have permanent effects on employment and output by altering credit supply conditions to firms. To save on space, mathematical proofs, statistical tests and data sources have been gathered in two separate appendices that can be examined on request. (J.E.L.: E2, E5). [source] The influence of ant-attendance on aphid behaviour investigated with the electrical penetration graph techniqueENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 1 2002Gisep Rauch Abstract For the mutualistic interaction between the aphid Metopeurum fuscoviride Stroyan (Homoptera: Aphididae) and the ant Lasius niger L. (Hymenoptera: Formicidae) it has been shown that ant-tended aphids develop faster, reproduce at a higher rate, and live longer than aphids not tended by ants. We used electrical penetration graphs (EPG) to investigate if behavioural patterns differ between ant-tended and untended M. fuscoviride during 8 h experiments. Measurements were made on adult aphids from four different ant-tended colonies that continued to be tended by L. niger during the experiments, and from four different colonies where ant workers were excluded several days before the start of the experiment and that were also not tended by ants during the experiments. Ants readily tended wired aphids and ant tending did not interfere with the EPG measurements. There were no significant differences in the duration of sieve element penetration or in any other analysed feeding-related EPG parameters between ant-tended and untended individuals. However, the quality of the EPG recordings did not allow the distinction between the EPG-waveform E1 (salivation only) and E2 (salivation and ingestion). These results suggest that the changes in life-history traits of ant-tended aphids do not result from changes in time of sieve element penetration waveforms. Alternative mechanisms may involve an increase in the rate of sap uptake or a higher effectiveness in nutrient uptake in the presence of ants. Our study demonstrates that the EPG technique is a useful tool to investigate the feeding behaviour of aphids during interactions with ants. [source] Vertical profiles of methanogenesis and methanogens in two contrasting acidic peatlands in central New York State, USAENVIRONMENTAL MICROBIOLOGY, Issue 8 2006Hinsby Cadillo-Quiroz Summary Northern acidic peatlands are important sources of atmospheric methane, yet the methanogens in them are poorly characterized. We examined methanogenic activities and methanogen populations at different depths in two peatlands, McLean bog (MB) and Chicago bog (CB). Both have acidic (pH 3.5,4.5) peat soils, but the pH of the deeper layers of CB is near-neutral, reflecting its previous existence as a neutral-pH fen. Acetotrophic and hydrogenotrophic methanogenesis could be stimulated in upper samples from both bogs, and phylotypes of methanogens using H2/CO2 (Methanomicrobiales) or acetate (Methanosarcinales) were identified in 16S rRNA gene clone libraries and by terminal restriction fragment length polymorphism (T-RFLP) analyses using a novel primer/restriction enzyme set that we developed. Particularly dominant in the upper layers was a clade in the Methanomicrobiales, called E2 here and the R10 or fen group elsewhere, estimated by quantitative polymerase chain reaction to be present at ,108 cells per gram of dry peat. Methanogenic activity was considerably lower in deeper samples from both bogs. The methanogen populations detected by T-RFLP in deeper portions of MB were mainly E2 and the uncultured euryarchaeal rice cluster (RC)-II group, whereas populations in the less acidic CB deep layers were considerably different, and included a Methanomicrobiales clade we call E1-E1,, as well as RC-I, RC-II, marine benthic group D, and a new cluster that we call the subaqueous cluster. E2 was barely detectable in the deeper samples from CB, further evidence for the associations of most organisms in this group with acidic habitats. [source] Methyl mercury influences growth-related signaling in MCF-7 breast cancer cellsENVIRONMENTAL TOXICOLOGY, Issue 1 2005Olga A. Sukocheva Abstract Environmental contaminants have been shown to alter growth-regulating signaling pathways through molecular mechanisms that are mainly unclear. Here we report that within a narrow concentration range (0.5,1 ,M) methyl mercury (MeHg) significantly stimulated growth of MCF-7 cells, induced Ca2+ mobilization, and activated extracellular signal,regulated kinase ½ (Erk1/2). MeHg modulated E2 -dependent stimulation of growth in a dose-dependent manner, although MeHg neither suppresses nor increases constitutive E2 metabolism. MeHg demonstrated weak estrogen receptor (ER),binding ability. However, long preincubation with antiestrogens LY156,758 and ICI164,384 decreased MeHg-induced foci formation, Ca2+ mobilization, and Erk1/2 activation, confirming involvement of ERs. The MeHg-induced increase in [Ca2+]i was observed to coincide with enhanced Erk1/2 phosphorylation. These data suggest that MeHg can significantly modulate the intracellular signaling environment in MCF-7 cells, resulting in a dose-dependent alteration of ER,mediated estrogenic capacity and therefore should be considered as a potential estrogen-disrupting compound. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 32,44, 2005. [source] Estrogenic effect of leachates and soil extracts from lysimeters spiked with sewage sludge and reference endocrine disruptersENVIRONMENTAL TOXICOLOGY, Issue 2 2002Halim Dizer Abstract Several experiments were conducted to evaluate the behavior and performance of some potential endocrine disrupters (ECDs). Two in vitro screening assays, one based on MCF7-cell proliferation (E-screen test) and the other on estrogenic receptor activity [enzyme-linked receptor assay (ELRA)], were used for the tests, which were done in lysimeters 80 cm in diameter with depths of 30 cm (shallow) or 90 cm (deep). A sandy soil was used to fill in all lysimeters, which were spiked on the surface with either: (a) a sewage sludge (SS) at a dose equivalent to 20 tons ha,1; (b) a mixture of reference ECDs, comprising 17,- and 17,-estradiol (E2), nonylphenol, octylphenol, and bisphenol A at doses 100 times higher than the maximum concentrations respectively found in the applied SS; or (c) a mixture of ECDs and SS. After percolation of the lysimeters with rain and/or artificial water, five leachates were sampled from each lysimeter during a period of 210 days. Immediately after the lysimeter percolation experiments, four and six soil fractions were dissected from, respectively, the 30-cm and 90-cm lysimeters and extracted by water. Both the leachate and soil extract samples were analyzed for their estrogenicity using the assays indicated above. The E-screen assay was highly sensitive only for some leachate and extract samples but gave no response for most leachates and soil extracts. The results of the ELRA assay suggests a significantly higher estrogenicity of leachate samples from shallow lysimeters compared with that of leachates from deep lysimeters. In contrast, the estrogenic effect measured for soil extracts of shallow lysimeters was lower than that measured for soil extracts of deep lysimeters. The results of the E-screen assay suggests the occurrence of a fast mobilization of applied ECDs and a moderate retardation effect of native ECDs contained in applied SS in the sandy soil used in the lysimeters. In lysimeters spiked with a mixture of SS and ECDs, the washing-out effect of ECDs in the first leachate fraction decreased, but the distribution of ECDs in the lysimeters increased. The relatively high estrogenic impact measured for soil water extracts suggests that the ECDs were mostly associated with water-soluble fractions of organic matter and/or water-suspended fractions of the mineral soil matrix. The application of SS to agricultural and forest fields may determine the immobilization of ECDs in soil or their movement to surface and/or groundwater. Therefore, an endocrine risk of exposure exists for the water and soil organisms. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 105,112, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10038 [source] Effects of 17 ,-estradiol exposure on Xenopus laevis gonadal histopathologyENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2010Jeffrey C. Wolf Abstract The natural estrogen 17 ,-estradiol (E2) is a potential environmental contaminant commonly employed as a positive control substance in bioassays involving estrogenic effects. The aquatic anuran Xenopus laevis is a frequent subject of reproductive endocrine disruptor research; however, histopathological investigations have tended to be less than comprehensive. Consequently, a study was designed to characterize gross and microscopic changes in the gonads of X. laevis as a result of E2 exposure. Additional goals of this study, which consisted of three separate experiments, included the standardization of diagnostic terminology and criteria, the validation of statistical methodology, and the establishment of a half maximal effective concentration (EC50) for E2 as defined by an approximately 50% conversion of presumptive genotypic males to phenotypic females. In the first experiment, frogs were exposed to nominal concentrations of 0, 0.2, 1.5, or 6.0,µg/L E2. From these experimental results and those of a subsequent range finding trial, the EC50 for E2 was determined to be approximately 0.2,µg/L. This E2 concentration was utilized in the other two experiments, which were performed at different facilities to confirm the reproducibility of results. Experiments were conducted according to Good Laboratory Practice guidelines, and the histopathologic evaluations were peer reviewed by an independent pathologist. Among the three trials, the histopathological findings that were strongly associated with E2-exposure (p,<,0.001 to 0.0001) included an increase in the proportion of phenotypic females, mixed sex, dilated testis tubules, dividing gonocytes in the testis, and dilated ovarian cavities in phenotypic ovaries. A comparison of the gross and microscopic evaluations suggested that some morphologic changes in the gonads may potentially be missed if studies rely entirely on macroscopic assessment. Environ. Toxicol. Chem. 2010;29:1091,1105. © 2010 SETAC [source] Time-Dependent transcriptional profiles of genes of the hypothalamic-pituitary-gonadal axis in medaka (Oryzias latipes) exposed to fadrozole and 17,-trenboloneENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2008Xiaowei Zhang Abstract Both the anabolic androgen 17,-trenbolone (TRB) and the aromatase inhibitor fadrozole (FAD) can cause decreased plasma concentrations of estrogen (E2) and reduce fecundity of fish. However, the underlying mechanisms and the molecular pathways involved are largely unknown. The present study was designed to assess time-dependent effects of FAD and TRB on the transcriptional responses of the hypothalamic-pituitary-gonadal (HPG) axis of Japanese medaka (Oryzias latipes). Fourteen-week-old Japanese medaka were exposed to 50 ,g FAD/L or 2 ,g TRB/L in a 7-d static renewal test, and the expression profiles of 36 HPG axis genes were measured by means of a medaka HPG real-time reverse-transcription polymerase chain reaction array after 8 h, 32 h, or 7 d of exposure. Exposure to TRB or FAD caused lesser fecundity of Japanese medaka and down-regulated transcription of vitellogenin and choriogenin (CHG) gene expression in the liver of females. Exposure to FAD for 8 h resulted in an 8-fold and 71-fold down-regulation of expression of estrogen receptor , and choriogenin L (CHG L), respectively, in female liver. 17,-Trenbolone caused similar down-regulation of these genes, but the effects were not observed until 32 h of exposure. These results support the hypothesis that FAD reduces plasma E2 more quickly by inhibiting aromatase enzyme activity than does TRB, which inhibits the production of the E2 precursor testosterone. Exposure to FAD and TRB resulted in rapid (after 8 h) down-regulation of luteinizing hormone receptor and low-density-lipoprotein receptor in the testis to compensate for excessive androgen levels. Overall, the molecular responses observed in the present study differentiate the mechanisms of the reduced fecundity by TRB and FAD. [source] Evaluation of estrogenic activity of phthalate esters by gene expression profiling using a focused microarray (estrarray®),ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2008Meher Parveen Abstract Phthalates are used industrially as plasticizers and are known to contaminate natural environments, mostly as di-ester or mono-ester complexes. Because they are structurally similar to natural estrogens, they could act as endocrine disruptors. Here, we used a DNA microarray containing estrogen responsive genes (EstrArray®) to examine gene expression profiles in MCF-7 cells treated with 10 ,M butylbenzyl phthalate (BBP), dibutyl phthalate (DBP), diethyl phthalate (DEP), and diisopropyl phthalate (DIP) along with the natural estrogen 17,-estradiol ([E2], 10 nM). The profiles for phthalate esters and E2 were examined by correlation analysis using correlation coefficients (r -values) and cluster analysis. We found that BBP showed the highest correlation with E2 (r = 0.85), and DEP and DIP showed moderate r -values (r = 0.52 and r = 0.49, respectively). Dibutyl phthalate exhibited the lowest (but still significant) correlation with E2 (r = 0.36). Furthermore, among the pairs of chemicals, DEP-DIP and DIP-DBP showed very high correlations (r = 0.90 and r = 0.80, respectively), and the other pairs showed moderate relationships, which reflected how structurally close they are to each other. The analysis of six functional groups of genes (enzymes, signaling, proliferation, transcription, transport, and others) indicated that the genes belonging to the enzyme, transcription, and other functional groups showed common responses to phthalate esters and E2. Although the effect of BBP was similar to that of E2, the other phthalate esters showed different types of effects. These results indicate that the structure of estrogenic chemicals is strongly related to their estrogenic activity and can be evaluated by appropriate grouping of the responsive genes by focused microarray analysis. [source] Ultra-trace analysis of multiple endocrine-disrupting chemicals in municipal and bleached kraft mill effluents using gas chromatography,high-resolution mass spectrometryENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2008Michael G. Ikonomou Abstract A comprehensive gas chromatographic,high-resolution mass spectrometric (GC-HRMS),based method was developed that permitted the simultaneous determination of 30 estrogenic endocrine-disrupting chemicals (EDCs) and related compounds, including surfactants, biogenic and synthetic steroids, fecal sterols, phytoestrogens, and plasticizers, in wastewater. Features of the method include low sample volume (,40 ml), optimized Florisil® cleanup to minimize matrix interferences and optimized analyte derivatization to improve sensitivity via GC-HRMS. Detection limits were in the low- to mid-ng/L range, and recoveries were greater than 60% for most target analytes. This new method allows for high throughput analysis of many organic wastewater contaminants in a complex matrix with relative standard deviation of less than 15% for most measurable compounds. The applicability of the method was demonstrated by examining wastewater samples from different origins. Compounds such as di(2-ethylhex-yl)phthalate, cholesterol, cholestanol, and other cholesterol derivatives were measured in much higher concentrations in untreated sewage and were reduced substantially in concentration by the treatment process. However, steroidal compounds, particularly estrone (E1), 17,-estradiol (E2), and estriol (E3), as well as plant sterols (except stigmastanol), were greater in the treated municipal wastewater versus the untreated effluent. Plant and fungi sterols, stigmastanol and ergosterol, were found largely associated with bleached kraft mill effluent (BKME) as compared to the municipal effluents. [source] Fate of estrogens and xenoestrogens in four sewage treatment plants with different technologies,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2008Guang-Guo Ying Abstract The fate and removal of the estrogens 17,-estradiol (E2), estrone (E1), and 17,-ethynylestradiol (EE2) and of the xenoestrogens bisphenol A (BPA), 4- tert -octylphenol (4- t -OP), 4-nonylphenol (4-NP), and nonylphenol mono- and diethoxylate (NPEO1 and NPEO2, respectively) were investigated in four South Australian sewage treatment plants (STPs; plants A,D) with different treatment technologies. The concentrations in the effluent from the two-year survey were similar to those reported in other studies. In the effluent, 4-NP, NPEO1, and NPEO2 had total concentrations up to 8 ,g/L, which were much higher than those of BPA and 4-t-OP. Estrone had the highest concentrations among the three estrogens, ranging between 13.3 and 39.3 ng/L, whereas the concentrations for E2 and EE2 varied between 1.0 and 4.2 ng/L and between 0.1 and 1.3 ng/L, respectively. The removal rates for the estrogens and xenoestrogens were variable but consistent with the plant performance parameters (biochemical oxygen demand, suspended solids, and ammonia). Considering all the estrogenic compounds analyzed in the present study, plant D, with a series of anaerobic and aerobic lagoons, was the least efficient of the four STPs in the removal of these compounds. The removal rates for 4-NP, NPEO1, and NPEO2 within the plants were 92% for plant A, with conventional activated sludge treatment; 80% for plant B, with two oxidation ditches; 70% for plant C, with three bioreactors; and 64% for plant D, with 10 lagoons in series. Comparatively, the removal of estrogens was lower, with rates ranging between 47 and 68% for E2 at the four plants. Both E1 and EE2 were more persistent during treatment, especially in plants C and D. [source] Aqueous exposure to 4-nonylphenol and 17,-estradiol increases stress sensitivity and disrupts ion regulatory ability of juvenile Atlantic salmonENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2007Darren T. Lerner Abstract Population declines of wild Atlantic salmon have been attributed to an array of anthropogenic disturbances, including dams, commercial and recreational fishing, habitat loss, and pollution. Environmental contaminants in particular, can act as environmental stressors on fish, typically causing disruption of ion homeostasis due to their close association with the aquatic environment. To examine the effects of the xenoestrogen 4-nonylphenol (NP) or 17,-estradiol (E2) on stress sensitivity and ion regulation, we exposed juvenile Atlantic salmon continuously for 21 d to either 10 or 100 ,g/L NP (NP-L or NP-H), 2 ,g/L E2 (positive control), or vehicle control during the parr-smolt transformation in April. After treatment, fish were sampled in freshwater (FW), transferred to 30, seawater (SW) for 24 h, or subjected to a handling stress. Estradiol and NP-H increased plasma vitellogenin in males and females, and E2 increased gonadosomatic index only in males. In FW, E2 reduced sodium potassium,activated adenosine triphosphatase activity as well as plasma levels of growth hormone, insulin-like growth factor I, and triiodothyronine. Both E2 and NP-H reduced plasma sodium in FW and increased plasma chloride in SW. Plasma Cortisol levels pre- and poststressor were significantly elevated by all treatments relative to controls, but only E2 increased plasma glucose before and after the stressor. These results indicate that exposure of anadromous salmonids to environmental estrogens heightens sensitivity to external stressors, impairs ion regulation in both FW and SW, and disrupts endocrine pathways critical for smolt development. [source] Effects of the estrogen agonist 17,-estradiol and antagonist tamoxifen in a partial life-cycle assay with zebrafish (Danio rerio)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2007Leo T. M. van der Ven Abstract A partial life-cycle assay (PLC) with zebrafish (Danio rerio) was conducted to identify endocrine-disrupting effects of 17,-estradiol (E2) and tamoxifen (TMX) as reference for estrogen agonist and antagonist activity. Adult zebrafish were exposed for 21 d and offspring for another 42 d, allowing differentiation of gonads in control animals. The assessed end points included reproductive variables (egg production, fertilization, and hatching), gonad differentiation of juveniles, histopathology, and vitellogenin (VTG) expression. With E2, the most sensitive end points were feminization of offspring (at 0.1 nM) and increased VTG production in males (at 0.32 nM). At 1 nM, decreased F1 survival, increased F1 body length and weight, VTG-related edema and kidney lesions, and inhibited spermatogenesis were observed. Oocyte atresia occurred at even higher concentrations. Exposure to TMX resulted in specific effects at an intermediate test concentration (87 nM), including oocyte atresia with granulosa cell transformation and disturbed spermatogenesis (asynchrony within cysts). In F1, decreased hatching, survival, and body weight and length as well as decreased feminization were observed. Decreased vitellogenesis and egg production in females and clustering of Leydig cells in males occurred at higher concentrations. Toxicological profiles of estrogen agonists and antagonists are complex and specific; a valid and refined characterization of endocrine activity of field samples therefore can be obtained only by using a varied set of end points, including histology, as applied in the presented PLC. Evaluation of only a single end point can easily produce under- or overestimation of the actual hazard. [source] Organohalogen contaminants and reproductive hormones in incubating glaucous gulls (Larus hyperboreus) from the Norwegian ArcticENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2006Jonathan Verreault Abstract Organohalogen contaminants detected globally in avian wildlife, including populations from the Arctic, have been related to various reproductive hormone potencies, and altered hormonal balance and functions. Besides legacy organochlorine (OC) substances, that is, polychlorinated biphenyls (PCBs) and OC pesticides and by-products, endocrine-disruptive properties have been defined for chemicals of new and emerging environmental concern, such as polybrominated diphenyl ethers (PBDEs) and metabolically derived products like methylsulfonyl (MeSO2)- and hydroxyl (OH)-PCBs. We investigated the relationships between plasma concentrations of selected legacy OCs, PBDEs, and MeSO2 - and OH-PCB metabolites and the circulating reproductive hormones testosterone (T), 17,-estradiol (E2), and progesterone (P4) in incubating male and female glaucous gulls (Larus hyperboreus) from the Norwegian Arctic. Principal component and regression analyses demonstrated that P4 levels in male glaucous gulls were associated positively with variations of sum (,) PCB, dichloro-diphenyl-trichloroethane (,DDT), chlordane (,CHL), and ,PBDE concentrations, which were the most recalcitrant organohalogens determined in glaucous gulls. No such relationship was found for female glaucous gulls as well as between concentrations of any of the selected organohalogens and levels of T for both sexes. The E2 was not detected in any plasma samples. Present results were highly suggestive that exposure to high organohalogen concentrations in glaucous gulls, particularly the most persistent compound classes, may have the potential to interfere with steroidogenesis and impinge on circulating P4 homeostasis. Because significant effects were found in males exclusively, it cannot be completely ruled out that male glaucous gulls are more sensitive than females to organohalogen-mediated alteration of P4 synthesis and breakdown. [source] Comparison of response to 17,-estradiol and 17,-trenbolone among three small fish speciesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2006Masanori Seki Abstract Three small fish species, medaka (Oryzias latipes), fathead minnow (Pimephales promelas), and zebrafish (Danio rerio), were exposed to an estrogen, 17,-estradiol (E2), and an androgen, 17,-trenbolone (TB), for 21 d under flow-through conditions to compare the susceptibility among these three small fish species to the substances. Effects on gross morphology, including secondary sex characteristics and gonadosomatic index, as well as on blood or liver vitellogenin (VTG) levels were assessed. In E2 exposures, significant increases in estrogenic activity were observed in both sexes of all three fish species. The lowest-observedeffect concentrations (LOECs) of E2 for VTG induction in males of medaka, fathead minnow, and zebrafish were less than or equal to 8.94, 28.6, and 85.9 ng/L, respectively. In TB exposures, we observed masculinization of secondary sex characteristics in females as a result of the androgenic activity of TB in medaka with a LOEC of 365 ng/L and in fathead minnow with a LOEC of 401 ng/L. We also found VTG reduction in females of all three fish species. These results suggest that the susceptibility of medaka to estrogenic chemicals may be higher than those of fathead minnow and zebrafish and that the susceptibility of medaka to androgenic chemicals may be almost equal to that of fathead minnow in the 21-d fish assay. [source] Impact of activated sludge-derived colloidal organic carbon on behavior of estrogenic agonist recombinant yeast bioassayENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2005R. David Holbrook Abstract The impact of size-fractionated colloidal organic carbon (COC) originating from a biological wastewater treatment facility on the sensitivity of the yeast estrogen screen (YES) bioassay containing the human estrogen receptor (hER) gene was evaluated. Dose-response curves of serially diluted 17,-estradiol (E2), both in the presence and absence of COC, were generated by the YES bioassay. The concentration of E2 leading to a 50% YES response (effective concentration 50%, or EC50) was used to evaluate quantitatively the estrogenic activity of the different COC-E2 mixtures. The EC50 values for all COC size fractions, including COC-free samples (<1 kD), were statistically greater than the controls using Milli-Q water. Normalized EC50 values significantly increased as a function of COC concentration for the larger size fractions (>0.22 ,m), but were not significantly affected by smaller COC material at environmental levels (1,5 mg/L), while both colloidal polysaccharide concentrations and colloidal fluorophores (measured at an excitation/emission wavelength pair of 350 nm/450 nm) appear to have an important role in the sensitivity of the YES bioassay. Estimates of the colloid-associated E2 fraction did not predict accurately increases in EC50 values. Matrix effects of the specific environment being tested with the YES bioassay need to be evaluated closely due to the sensitivity of the hER and reporter plasmid. [source] Photodegradation of common environmental pharmaceuticals and estrogens in river waterENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2005Angela Yu-Chen Lin Abstract Photodegradation rates of five pharmaceuticals (gemfibrozil, ibuprofen, ketoprofen, naproxen, and propranolol) and of four estrogens (estriol, estrone [E1], 17,-estradiol [E2], and 17,-ethinylestradiol [EE2]), which are common contaminants in the aquatic environment, were measured in both purified and river water at environmentally relevant concentrations (1,2 ,g/L) and different oxygen concentrations. Solutions were irradiated with a xenon arc lamp (765 W/m2; 290 nm < , < 700 nm) and analyzed using a high-performance liquid chromatography-tandem mass spectrometry method with electrospray ionization for pharmaceuticals and atmospheric pressure photoionization for estrogens. In river water, half-lives were 4.1 h for ketoprofen, 1.1 min for propranolol, 1.4 h for naproxen, 2 to 3 h for estrogens, and 15 h for gemfibrozil and ibuprofen. In air-saturated purified water, rates generally were slower except for that of ketoprofen, which reacted with a half-life of 2.5 min. Naproxen, propranolol, and E1 reacted with half-lives of 1.9, 4.4, and 4.7 h, respectively. The EE2, estriol, E2, gemfibrozil, and ibuprofen reacted with half-lives of 28.4, 38.2, 41.7, 91.4, and 205 h, respectively. The presence of oxygen doubled the direct photolysis rates of naproxen and propranolol. In nonautoclaved river water, 80% of E2 rapidly biotransformed to E1 within less than 20 min, whereas all other compounds remained stable over 22 h. [source] Plasma sex steroid concentrations and gonadal aromatase activities in African clawed frogs (Xenopus laevis) from South AfricaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2004Markus Hecker Abstract Adult African clawed frogs (Xenopus laevis) were collected from a corn-growing region (CGR) and a non-corn-growing region (NCGR) with different exposure profiles for atrazine and related triazines. Physical, chemical, and biological parameters from the catchment areas were also measured. Frogs were surveyed for possible effects of exposure to triazine herbicides on plasma testosterone (T) and estradiol (E2) titers, gonadal aromatase activity, and gonad growth (GSI). Concentrations of both T and E2 varied among locations and were correlated to some accessory factors, such as pH, several ions, and metals. Greatest median plasma T concentrations (males: 19 ng/ml; females: 16 ng/ml) occurred in frogs inhabiting NCGR as compared to those from the CGR (males: 4 ng/ml; females: 1 ng/ml). Median E2 concentrations were also greater in frogs collected from the NCGR (males: 3 ng/ml; females: 28 ng/ml) than those in frogs from the CGR (males: 2 ng/ml; females: 5 ng/ml). Because some exposure to agricultural chemicals at both regions occurred, as did simultaneous exposures to multiple chemicals, a regression analysis was employed. Negative correlations were observed between plasma T concentrations and concentrations of atrazine, deisopropylatrazine, deethylatrazine, and tertbuthylazine in females and between T and diaminochlorotriazine in males. Estradiol in females exhibited a significant negative correlation with atrazine and deethylatrazine. No correlations were observed between gonadal aromatase activity or GSI and any of the agricultural chemicals measured. Median aromatase activities in ovaries varied among sampling sites ranging from 7 to >3,000 times greater than those in males when measurable. Testicular aromatase activity was below the detection limit of the assay in male frogs at most of the sites. Although exposure to agricultural inputs did not affect aromatase activities, effects of atrazine or coapplied pesticides on sex steroid homeostasis cannot be excluded at this point. [source] The potential for estradiol and ethinylestradiol to sorb to suspended and bed sediments in some English riversENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2002Karlijn I. E. Holthaus Abstract The endocrine-disrupting impact of steroid estrogens on fish will be strongly influenced by their distribution between sediment and water. Laboratory studies were performed to investigate the potential for sorption of 17,-estradiol (E2) and 17,-ethinylestradiol (EE2) to bed and suspended sediments taken from five British rivers. Sediment material was collected from the Rivers Aire and Calder (located in urban and industrialized areas in Yorkshire, UK), the River Thames (at a relatively rural site in Oxfordshire, UK), and from the estuaries of the Rivers Tees and Tyne. Using anaerobic conditions to inhibit biodegradation, it was found that 80 to 90% of binding to bed sediments was complete within 1 d, but that an equilibrium had not been reached after 2 d. Bed sediments gave distribution coefficients (Kd) ranging from 4 to 74 L/kg for E2 and from 8 to 121 L/kg for EE2 for samples taken over a range of seasons and locations. Sorption to suspended sediment gave Kd values ranging from 21 to 122 L/kg for E2 and 19 to 260 L/kg for EE2. However, these Kd values suggest less than 1% removal of the steroid estrogens from the aqueous phase given the ambient suspended sediment concentration. In the bed sediments, higher Kd values were associated with smaller particle size and higher organic carbon content. In most cases, the Kd values obtained for EE2 were higher than those for E2 by a factor of up to three. [source] In vitro assessment of potential mechanism-specific effects of polybrominated diphenyl ethersENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2002Daniel L. Villeneuve Abstract This study examined the ability of environmentally relevant concentrations of 10 different polybrominated diphenyl ethers (PBDEs) to induce aryl hydrocarbon receptor (AhR)-and estrogen receptor (ER)-mediated gene expression in vitro. It also examined the ability of PBDEs to displace steroid hormones from serum proteins in vitro. At concentrations ranging up to 880 ng/ml, none of the PBDEs significantly displaced tritiated 17,-estradiol (E2) or testosterone from hormone-stripped carp serum. At concentrations ranging up to 500 ng/ml, 9 of 10 PBDEs tested failed to induce ER- or AhR-mediated gene expression in MVLN and H4IIE-luc cells, respectively. One congener, 3,3,,4,4,,5-pentabromodiphenylether (BDE 126), induced significant AhR-mediated gene expression at 500 ng/ml, but the magnitude of induction was only 13% of that caused by 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD). Overall, the PBDEs tested were found to be at least 200,000 times less potent than TCDD and 50,000 times less potent than E2 for inducing AhR- and ER-mediated gene expression, respectively. [source] Development of a fish reporter gene system for the assessment of estrogenic compounds and sewage treatment plant effluentsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2002Gabriele E. Ackermann Abstract This study reports on the development and application of a fish-specific estrogen-responsive reporter gene assay. The assay is based on the rainbow trout (Oncorhynchus mykiss) gonad cell line RTG-2 in which an acute estrogenic response is created by cotransfecting cultures with an expression vector containing rainbow trout estrogen receptor a complementary DNA (rtER, cDNA) in the presence of an estrogen-dependent reporter plasmid and an estrogen receptor (ER) agonist. In a further approach, RTG-2 cells were stably transfected with the rtER, cDNA expression vector, and clones responsive to 17,-estradiol (E2) were selected. The estrogenic activity of E2, 17,-ethinylestradiol, 4-nonylphenol, nonylphenoxy acetic acid, 4- tert -octylphenol, bisphenol A, o,p,-DDT, p,p,-DDT, o,p,-2,2-bis(chlorophenyl)-1,1-dichloroethylene (o,p,-DDE), p,p,-DDE, o,p,-2,2-bis(chlorophenyl)-1,1-di-chloroethane (o,p,-DDD), p,p,-DDD, and p,p,-2,2-bis(chlorophenyl)acetic acid (p,p,-DDA) was assessed at increasing concentrations. All compounds except o,p,-DDT, p,p,-DDE, and p,p,-DDA showed logistic dose-response curves, which allowed the calculation of lowest-observed-effect concentrations and the concentrations at which half-maximal reporter gene activities were reached. To check whether estrogen-responsive RTG-2 cells may be used to detect the estrogenic activity of environmental samples, an extract from a sewage treatment plant (STP) effluent was assessed and found to have estrogenic activity corresponding to the transcriptional activity elicited by 0.05 nM of E2. Dose-response curves of nonylphenol, octylphenol, bisphenol A, and o,p,-DDD revealed that the RTG-2 reporter gene assay is more sensitive for these compounds when compared to transfection systems recombinant for mammalian ERs. These differences may have an effect on the calculation of E2 equivalents when estrogenic mixtures of known constitution, or environmental samples, such as STP effluents, are assessed. [source] The potential for estradiol and ethinylestradiol degradation in english riversENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2002Monika D. Jürgens Abstract Water samples were collected in spring, summer, and winter from English rivers in urban/industrial (River Aire and River Calder, Yorkshire, UK) and rural environments (River Thames, Oxfordshire, UK) to study the biodegradation potential of the key steroid estrogen 17,-estradiol (E2) and its synthetic derivate ethinylestradiol (EE2). Microorganisms in the river water samples were capable of transforming E2 to estrone (E1) with half-lives of 0.2 to 9 d when incubated at 20°C. The E1 was then further degraded at similar rates. The most rapid biodegradation rates were associated with the downstream summer samples of the River Aire and River Calder. E2 degradation rates were similar for spiking concentrations throughout the range of 20 ng/L to 500 ,g/L. Microbial cleavage of the steroid ring system was demonstrated by release of radiolabeled CO2 from the aromatic ring of E2 (position 4). When E2 was degraded, the loss of estrogenicity, measured by the yeast estrogen screen (YES) assay, closely followed the loss of the parent molecule. Thus, apart from the transient formation of E1, the degradation of E2 does not form other significantly estrogenic intermediates. The E2 could also be degraded when incubated with anaerobic bed sediments. Compared to E2, EE2 was much more resistant to biodegradation, but both E2 and EE2 were susceptible to photodegradation, with half-lives in the order of 10 d under ideal conditions. [source] Intralesional bovine papillomavirus DNA loads reflect severity of equine sarcoid diseaseEQUINE VETERINARY JOURNAL, Issue 4 2010R. HARALAMBUS Summary Reasons for performing study: Sarcoids are nonmetastasising, yet locally aggressive skin tumours that constitute the most frequent neoplasm in equids. Infection by bovine papillomaviruses types 1 and 2 (BPV-1, BPV-2) has been recognised as major causative factor in sarcoid pathogenesis, but a possible correlation of intralesional virus load with disease severity has not been established thus far. Hypothesis: Given the pathogenic role of BPV-1 and BPV-2 in sarcoid disease, we suggest that intralesional viral DNA concentration may reflect the degree of affection. Methods: Severity of disease was addressed by recording the tumour growth kinetics, lesion number and tumour type for 37 sarcoid-bearing horses and one donkey. Viral load was estimated via quantitative real-time PCR (qPCR) of the E2, E5, L1 and L2 genes from the BPV-1/-2 genome for one randomly selected lesion per horse and correlated with disease severity. Results: Quantitative PCR against E2 identified viral DNA concentrations ranging from 0,556 copies/tumour cell. Of 16 horses affected by quiescent, slowly growing single tumours or multiple mild-type lesions, 15 showed a viral load up to 1.4 copies per cell. In stark contrast, all equids (22/22) bearing rapidly growing and/or multiple aggressive sarcoids had a viral load between 3 and 569 copies per cell. Consistent results were obtained with qPCR against E5, L1 and L2. Conclusions: While tumours of the same clinical type carried variable virus load, confirming that viral titre does not determine clinical appearance, we identified a highly significant correlation between intralesional viral load and disease severity. Potential relevance: The rapid determination of BPV viral load will give a reliable marker for disease severity and may also be considered when establishing a therapeutic strategy. [source] Suppression of inflammatory responses by celastrol, a quinone methide triterpenoid isolated from Celastrus regeliiEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2009D. H. Kim Abstract Background, Celastrol, a quinone methide triterpenoid isolated from the Celastraceae family, exhibits various biological properties, including chemopreventive, antioxidant and neuroprotective effects. In this study, we showed that celastrol inhibits inflammatory reactions in macrophages and protects mice from skin inflammation. Materials and methods, Anti-inflammatory effects of celastrol (0,1 ,M) were examined in lipopolysaccharide (LPS)-stimulated RAW 264·7 macrophages. To investigate the effects of celastrol (0,50 ,g per mice) in vivo, activation of myeloperoxidase (MPO) and histological assessment were examined in the 12- O -tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear oedema model. Results, Our in vitro experiments showed that celastrol suppressed not only LPS-stimulated generation of nitric oxide and prostaglandin E2, but also expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW264·7 cells. Similarly, celastrol inhibited LPS-induced production of inflammatory cytokines, including tumour necrosis factor-, and interleukin-6. In an animal model, celastrol protected mice from TPA-induced ear oedema, possibly by inhibiting MPO activity and production of inflammatory cytokines. Conclusions, Our data suggest that celastrol inhibits the production of inflammatory mediators and is a potential target for the treatment of various inflammatory diseases. [source] Pulmonary stromal cells induce the generation of regulatory DC attenuating T-cell-mediated lung inflammationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2008Qian Li Abstract The tissue microenvironment may affect the development and function of immune cells such as DC. Whether and how the pulmonary stromal microenvironment can affect the development and function of lung DC need to be investigated. Regulatory DC (DCreg) can regulate T-cell response. We wondered whether such regulatory DC exist in the lung and what is the effect of the pulmonary stromal microenvironment on the generation of DCreg. Here we demonstrate that murine pulmonary stromal cells can drive immature DC, which are regarded as being widely distributed in the lung, to proliferate and differentiate into a distinct subset of DCreg, which express high levels of CD11b but low levels of MHC class II (I-A), CD11c, secrete high amounts of IL-10, NO and prostaglandin E2 (PGE2) and suppress T-cell proliferation. The natural counterpart of DCreg in the lung with similar phenotype and regulatory function has been identified. Pulmonary stroma-derived TGF-, is responsible for the differentiation of immature DC to DCreg, and DCreg-derived PGE2 contributes to their suppression of T-cell proliferation. Moreover, DCreg can induce the generation of CD4+CD25+Foxp3+ Treg. Importantly, infusion with DCreg attenuates T-cell-mediated eosinophilic airway inflammation in vivo. Therefore, the pulmonary microenvironment may drive the generation of DCreg, thus contributing to the maintenance of immune homoeostasis and the control of inflammation in the lung. [source] Intraocular injection of tamoxifen-loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Yvonne de Kozak Abstract In this study, we tested the efficiency of an intravitreal injection of tamoxifen, a non-steroidal estrogen receptor modulator, in retinal soluble antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). To increase the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene glycol (PEG)-coated nanoparticles (NP-PEG-TAM). The localization of the nanoparticles within the eye was investigated using fluorescent-labeled PEG-coated nanoparticles after injection into the vitreous cavity of rats with EAU. Some nanoparticles were distributed extracellularly throughout the ocular tissues, others were concentrated in resident ocular cells and in infiltrating macrophages. Whereas the injection of free tamoxifen did not alter the course of EAU, injection of NP-PEG-TAM performed 1,2,days before the expected onset of the disease in controls resulted in significant inhibition of EAU. NP-PEG-TAM injection significantly reduced EAU compared to injection of NP-PEG-TAM with 17,-estradiol (E2), suggesting that tamoxifen is acting as a partial antagonist to E2. Diminished infiltration by MHC class,II+ inflammatory cells and low expression of TNF-,, IL-1,, and RANTES mRNA were noted in eyes of NP-PEG-TAM-treated rats. Intravitreal injection of NP-PEG-TAM decreased S-Ag lymphocyte proliferation, IFN-, production by inguinal lymph node cells, and specific delayed-type hypersensitivity indicative of a reduced Th1-type response. It increased the anti-S-Ag IgG1 isotype indicating an antibody class switch to Th2 response. These data suggest that NP-PEG-TAM inhibition of EAU could result from a form of immune deviation. Tamoxifen-loaded nanoparticles may represent a new option for the treatment of experimental uveitis. [source] T cell costimulation by the hepatitis C virus envelope protein E2 binding to CD81 is mediated by LckEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2003Elisabetta Soldaini Abstract Binding of the hepatitis C virus (HCV) envelope protein E2 to CD81 provides a costimulatory signal for human T cells. This phenomenon may play a role in liver damage and autoimmune manifestations associated with HCV infection. Here we show that cross-linking of CD81 by HCV E2 induced a calcium flux in T cells that depends on Lck since it was blocked by PP1 and absent in Lck-deficient Jurkat T cells. In wild-type Jurkat cells, Lck was activated by CD81 cross-linking, and CD81, like Lck, was found in lipid rafts. Indeed, the integrity of the raft compartment was required for the induction of a calcium flux by E2, since methyl-,-cyclodextrin abolished this response. A requirement for TCR/CD3 expression was indicated by the absence of a calcium flux following E2 stimulation of TCR/CD3-deficient Jurkat cells. CD81 cross-linking increased and prolonged the anti-CD3-induced tyrosine phosphorylation of TCR, and of other proteins, indicating that the CD81-mediated signal converges with the TCR/CD3 signaling cascade at its most upstream step. In conclusion, we propose that the costimulatory effects of HCV E2 on T cells depend on CD81 cross-linking that activates Lck through raft aggregation and thus leads to enhanced TCR signaling. [source] | ||||||||||||||||||||||||||||||||||||||||