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Sample records for bromine-80m-labeled estrogens auger-electron

  1. Bromine-80m-labeled estrogens: Auger-electron emitting, estrogen receptor-directed ligands with potential for therapy of estrogen receptor positive cancers

    International Nuclear Information System (INIS)

    DeSombre, E.R.; Mease, R.C.; Hughes, A.; Harper, P.V.; DeJesus, O.T.; Friedman, A.M.

    1988-01-01

    A triphenylbromoethylene, 1,1-bis(p-hydroxyphenyl)-2-bromo-2-phenylethylene, Br-BHPE, and a bromosteroidal estrogen, 17α- bromovinylestradiol, BrVE 2 , were labeled with the Auger electron emitting nuclide bromine-80m, prepared by the [p,n] reaction with 80 Se. To assess their potential as estrogen receptor (ER) directed therapeutic substrates the bromine-80m labeled estrogens were injected into immature female rats and the tissue distribution studied at 0.5 and 2 hours. Both radiobromoestrogens showed substantial diethylstilbesterol (DES)-inhibitable localization in the ER rich tissues, uterus, pituitary, ovary and vagina at both time points. While the percent dose per gram tissue was higher for the Br-BHPE, the BrVE 2 showed higher tissue to blood ratios, especially at 2 hr, reflecting the lower blood concentrations of radiobromine following administration of the steroidal bromoestrogen. Comparing intraperitoneal, intravenous and subcutaneous routes of administration for the radiobromine labeled Br-BHPE, the intraperitoneal route was particularly advantageous to provide maximum, DES-inhibitable concentrations in the peritoneal, ER-rich target organs, the uterus, ovary and vagina. While uterine concentrations after BrBHPE were from 10--48% dose/g and after BrVE 2 were 15--25% dose/g, similar treatment with /sup 80m/Br as sodium bromide showed uniform low concentrations in all tissues at about the levels seen in blood. The effective specific activity of [/sup 80m/Br]BrBHPE, assayed by specific binding to ER in rat uterine cytosol, was 8700 Ci/mmole. 23 refs., 9 figs., 2 tabs

  2. Auger electron spectroscopy

    International Nuclear Information System (INIS)

    Gopalaraman, C.P.

    1975-01-01

    General features of electron excited Auger electron spectroscopy (AES) which is a nondestructive technique for the analysis of surfaces upto about 15 Adeg depth with a detection limit of about 0.1% of a monolayer. Methods of measuring the Auger electron energies and recent improvements in the instrumentation are reviewed. Typical energy resolution is found to be about 0.5% which is specially suited for the detection of light elements. It is widely used in metallurgy, surface chemistry and thin film studies. (K.B.)

  3. Auger electron spectroscopy of alloys

    International Nuclear Information System (INIS)

    Kuijers, F.J.

    1978-01-01

    This thesis describes how the surface compositions of some alloys can be determined by Auger Electron Spectroscopy (AES). The motivation for this research and the reasons for the choice of alloy systems studied are formulated. The theoretical background of AES is briefly discussed and the apparatus used and the experimental procedures applied are described. Four alloy systems have been investigated in this thesis - Ni-Cu and Pd - Ag (consisting of a component active in most cataytic reactions - Ni and Pd; and a component which is almost inactive for a number of reactions - Cu and Ag) and Pt - Pd and Pt-Ir (consisting of two active components). Knowledge of the surface composition of the various alloy systems is shown to be essential for the interpretation of catalytic results. (Auth./C.F.)

  4. Auger electron spectroscopy of alloy surfaces

    International Nuclear Information System (INIS)

    Overbury, S.H.; Somorjai, G.A.

    1975-03-01

    Regular solution models are used to predict surface segregation of the constituent of lowest surface free energy in homogeneous multicomponent systems. Analysis of the Auger electron emission intensities from alloys yield the surface composition and the depth distribution of the composition near the surface. Auger Electron Spectroscopy (AES) studies of the surface composition of the Ag--Au and Pb--In systems have been carried out as a function of bulk composition and temperature. Although these alloys have very different regular solution parameters their surface compositions are predictable by the regular solution models. (U.S.)

  5. PAES: Positron annihilation induced Auger electron spectrometer

    OpenAIRE

    Hugenschmidt, Christoph

    2015-01-01

    Positron annihilation induced Auger electron spectroscopy (PAES) is a newly developed application for surface studies with high elemental selectivity and exceptional surface sensitivity. The instrument is operated by the Technische Universität München and is located at NEPOMUC.

  6. PAES: Positron annihilation induced Auger electron spectrometer

    Directory of Open Access Journals (Sweden)

    Christoph Hugenschmidt

    2015-08-01

    Full Text Available Positron annihilation induced Auger electron spectroscopy (PAES is a newly developed application for surface studies with high elemental selectivity and exceptional surface sensitivity. The instrument is operated by the Technische Universität München and is located at NEPOMUC.

  7. A computer simulation of auger electron spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Ragheb, M S; Bakr, M H.S. [Dept. Of Accellerators and Ion Sources, Division of Basic Nuclear Sciences, NRC, Atomic Energy Authority, (Egypt)

    1997-12-31

    A simulation study of Auger electron spectroscopy was performed to reveal how far the dependency between the different parameters governing the experimental behavior affects the peaks. The experimental procedure followed by the AC modulation technique were reproduced by means of a computer program. It generates the assumed output Auger electron peaks, exposes them to a retarding AC modulated field and collects the resulting modulated signals. The program produces the lock-in treatment in order to demodulate the signals revealing the Auger peaks. It analyzes the spectrum obtained giving the peak positions and energies. Comparison between results of simulation and the experimental data showed good agreement. The peaks of the spectrum obtained depend upon the amplitude, frequency and resolution of the applied modulated signal. The peak shape is effected by the rise time, the slope and the starting potential of the retarding field. 4 figs.

  8. Auger Electron Therapy And Brachytherapy Tumor Treatment

    International Nuclear Information System (INIS)

    Laster, B.H.; Shani, G.

    2002-01-01

    Auger Electron Therapy (AET) is a binary approach for improving cancer radiotherapy. It involves the selective targeting of an atom to tumor cells using physiological pathway. The atom is then irradiated by a specific radiation that produces secondary radiation called Auger electrons. One of the problems associated with the clinical application of AET, is that the energy of the photons required for stimulating photoelectric absorption in most of the available high Z target atoms, is too low to achieve penetration through normal surrounding tissues to the depth of the tumor, when an external source is used. The solution is therefore the use of a brachytherapy technique. There are two other problems associated with the use of radiation as a cancer treatment. The first is the limitation on radiation dose to the normal tissue within the treatment volume. The second problem is the limitation imposed by the miniscule size of the critical target of the cell, namely the DNA (0.25% of the cell mass). The solution to the first problem can be achieved by using the brachytherapy technique. The second problem can be resolved by placing the radiation source in close position to the DNA. AET, as we apply it, provides the two solutions to the two problems. When a photon is absorbed by an electron in the K or L shell of an high Z atom, the electron is ejected from the atom, creating a vacancy in the shell. This vacancy is immediately filled with an electron from an upper shell. The energy difference between the two shells is sometimes emitted as an x-ray, however, frequently the energy is transferred to an outer shell electron that is emitted as an Auger electron. These electrons are emitted at energies of up to ∼30 keV and therefore have a very short range in the cell. They will deposit all their energy within 20-30 nm from the point of emission. i.e. all the energy is deposited in the DNA. In our work indium is used as the high Z atom

  9. Auger electron spectroscopy studies of boron carbide

    International Nuclear Information System (INIS)

    Madden, H.H.; Nelson, G.C.; Wallace, W.O.

    1986-01-01

    Auger electron spectroscopy has been used to probe the electronic structure of ion bombardment (IB) cleaned surfaces of B 9 C and B 4 C samples. The shapes of the B-KVV and C-KVV Auger lines were found to be relatively insensitive to the bulk stoichiometry of the samples. This indicates that the local chemical environments surrounding B and C atoms, respectively, on the surfaces of the IB cleaned samples do not change appreciably in going from B 9 C to B 4 C. Fracturing the sample in situ is a way of producing a clean representative internal surface to compare with the IB surfaces. Microbeam techniques have been used to study a fracture surface of the B 9 C material with greater spatial resolution than in our studies of IB surfaces. The B 9 C fracture surface was not homogeneous and contained both C-rich and B-rich regions. The C-KVV line for the C-rich regions was graphitic in shape. Much of the C-rich regions was found by IB to be less than 100 nm in thickness. The C-KVV line from the B-rich regions was carbidic and did not differ appreciably in shape from those recorded for the IB cleaned surfaces

  10. Chemical information from Auger electron spectroscopy

    International Nuclear Information System (INIS)

    Madden, H.H.

    1981-01-01

    The nature of chemical information in Auger electron spectroscopy (AES) data is reviewed with special emphasis on data from solid surface systems. Two strategies are most frequently used to extract this information: (i) measuring and analyzing energy (chemical) shifts in Auger peaks; and (ii) making use of the shapes of Auger signals to determine the chemical environment at the site of the initial core hole. Chemical shift data are primarily illustrated by highlighting the interaction of oxygen with solids; and analyses of these data based on core-level binding-energy shifts, relaxation, and hole--hole interactions are outlined and discussed. Auger transitions that involve valence electrons are usually those for which lineshapes are taken as indications of the local chemistry at the initial core-hole site. Attempts at extracting valence band density-of-states information from lineshapes are proving successful and this approach to the surface chemical information in AES is illustrated with the aid of examples dealing with the interaction of silicon with hydrogen and with oxygen. The use of the AES lineshapes simply as ''fingerprints'' of the core-hole-site chemistry is examined and illustrated by examples which include studies of silicon nitride properties, of solid surface properties related to catalytic reactions, and of passive films on iron. Auger decay activated desorption processes are briefly examined and found to promise new and unique chemical information when combined with conventional AES. Some gas phase AES studies are also briefly reviewed

  11. Interaction of measles virus vectors with Auger electron emitting radioisotopes

    International Nuclear Information System (INIS)

    Dingli, David; Peng, K.-W.; Harvey, Mary E.; Vongpunsawad, Sompong; Bergert, Elizabeth R.; Kyle, Robert A.; Cattaneo, Roberto; Morris, John C.; Russell, Stephen J.

    2005-01-01

    A recombinant measles virus (MV) expressing the sodium iodide symporter (NIS) is being considered for therapy of advanced multiple myeloma. Auger electrons selectively damage cells in which the isotope decays. We hypothesized that the Auger electron emitting isotope 125 I can be used to control viral proliferation. MV was engineered to express both carcinoembryonic antigen and NIS (MV-NICE). Cells were infected with MV-NICE and exposed to 125 I with appropriate controls. MV-NICE replication in vitro is inhibited by the selective uptake of 125 I by cells expressing NIS. Auger electron damage is partly mediated by free radicals and abrogated by glutathione. In myeloma xenografts, control of MV-NICE with 125 I was not possible under the conditions of the experiment. MV-NICE does not replicate faster in the presence of radiation. Auger electron emitting isotopes effectively stop propagation of MV vectors expressing NIS in vitro. Additional work is necessary to translate these observations in vivo

  12. A study of Al/Si interface by photoemission, Auger electron yield and Auger electron spectroscopies

    International Nuclear Information System (INIS)

    Kobayashi, K.L.I.; Barth, J.; Gerken, F.; Kunz, C.; Deutsches Elektronen-Synchrotron

    1980-06-01

    Photoemission, Auger electron yield and Auger electron spectra were observed for Al/Si(111) interfaces with various Al coverage prepared by successive deposition using a molecular beam source. The Al 3p derived states are introduced at around the top of the valence band by the Al coverage of less than one monolayer. The Al surface layer behaves as a 'metal' and the Fermi level is stabilized in the Al 3p derived states at about 0.3 eV above the top of the valence band of Si. The Schottky barrier height in this stage is about 0.8 eV and further increase in Al coverage does not change the barrier height. A covalent bonding model of the Al/Si interface based on the experimental results is proposed. The present result favors the on-top geometry of Al atoms on Si(111) surface among the geometries used in the pseudopotential calculation by Zhang and Schlueter. (orig.)

  13. Auger electron emitters: Insights gained from in vitro experiments

    International Nuclear Information System (INIS)

    Makrigiorgos, G.; Adelstein, S.J.; Kassis, A.I.

    1990-01-01

    This paper outlines the evolution of the current rationale for research into the biological effects of tissue-incorporated Auger electron emitters. The first section is a brief review of the research conducted by several groups in the last fifteen years. The second section describes the in vitro model used in our studies, dosimetric calculations, experimental techniques and recent findings. The third section focuses on the use of Auger electron emitters as in vitro microprobes for the investigation of the radiosensitivity of distinct subcellular components. Examination of the biological effects of the Auger electron emitter 125 I located in different cellular compartments of a single cell line (V 79 hamster lung fibroblast) verifies that DNA is the critical cell structure for radiation damage and that the sensitive sites are of nanometer dimensions. The data from incorporation of several Auger electron emitters at the same location within DNA suggest that there are no saturation effects from the decay of these isotopes (i.e. all the emitted energy is biologically effective) and provide some insight into which of the numerous physical mechanisms accompanying the Auger decay are most important in causing cell damage. Finally the implications of Auger electron emission for radiotherapy and radiation protection in diagnostic nuclear medicine are detailed and further research possibilities are suggested. (orig.)

  14. Physical design of the positron induced auger electron spectrometer

    International Nuclear Information System (INIS)

    Qin Xiubo; Jiang Xiaopan; Wang Ping; Yu Runsheng; Wang Baoyi; Wei Long

    2009-01-01

    Positron Annihilation Induced Auger Electron Spectroscopy (PAES) has several advantages over those excited by X-rays, high energy electrons or neutrons, such as excellent surface selectivity, high signal-to-noise ratio, low radiation damage,etc. A physical design of time of flight PAES (TOF-PAES) apparatus based on the Beijing Intense Slow Positron Beam (BIPB) is described in this paper. The positrons and electrons are transported in a 4 x 10 -3 T uniform magnetic field, and the gradient of magnetic field is designed to pluralize the Auger electrons emitted with 2π angle. The Auger electron energy is adjusted by a Faraday cage to optimize the energy resolution,which can be better than 2 eV. (authors)

  15. Auger electron and X-ray spectroscopy of hollow atoms

    NARCIS (Netherlands)

    Morgenstern, R; Johnson, RL; Schmidtbocking, H; Sonntag, BF

    1997-01-01

    Hollow atoms as formed during collisions of multiply charged ions on metallic, semiconducting and insulating surfaces have in recent years successfully been investigated by various spectroscopic methods: low- and high-resolution X-ray spectroscopy as well as high resolution Auger electron

  16. Photoion Auger-electron coincidence measurements near threshold

    International Nuclear Information System (INIS)

    Levin, J.C.; Biedermann, C.; Keller, N.; Liljeby, L.; Short, R.T.; Sellin, I.A.; Lindle, D.W.

    1990-01-01

    The vacancy cascade which fills an atomic inner-shell hole is a complex process which can proceed by a variety of paths, often resulting in a broad distribution of photoion charge states. We have measured simplified argon photoion charge distributions by requiring a coincidence with a K-LL or K-LM Auger electron, following K excitation with synchrotron radiation, as a function of photon energy, and report here in detail the argon charge distributions coincident with K-L 1 L 23 Auger electrons. The distributions exhibit a much more pronounced photon-energy dependence than do the more complicated non-coincident spectra. Resonant excitation of the K electron to np levels, shakeoff of these np electrons by subsequent decay processes, double-Auger decay, and recapture of the K photoelectron through postcollision interaction occur with significant probability. 17 refs

  17. Recommended Auger-electron kinetic energies for 42 elemental solids

    International Nuclear Information System (INIS)

    Powell, C.J.

    2010-01-01

    An analysis is presented of Auger-electron kinetic energies (KEs) from four data sources for 65 Auger transitions in 45 elemental solids. For each data source, a single instrument had been used to measure KEs for many elements. In order to compare KEs from two sources, it was necessary to recalibrate the energy scales of each instrument using recommended reference data. Mean KEs are given for most of the Auger transitions for which there were at least two independent measurements and for which differences from the mean KEs were considered acceptably small. In several cases, comparisons were made to published KE data to resolve discrepancies. We are able to recommend mean KEs for 59 Auger transitions from 42 elemental solids and to provide estimates of the uncertainties of these KEs. This compilation should be useful for the determination of chemical shifts of Auger peaks in Auger electron spectroscopy and X-ray photoelectron spectroscopy.

  18. Auger electron spectroscopy for the advanced student laboratory

    International Nuclear Information System (INIS)

    Greczylo, Tomasz; Mazur, Piotr; Debowska, Ewa

    2009-01-01

    This paper presents Auger electron spectroscopy with a retarding field analyser designed for an advanced physics experiment carried out in 'Physics Laboratory II' at the Institute of Experimental Physics, University of Wroclaw, Poland. The authors discuss the process of setting up the experiment and the results of the measurement of Auger spectra. The advantages and disadvantages of the apparatus are discussed along with its implementation in the teaching process

  19. Study of solute segregation at interfaces using Auger electron spectroscopy

    International Nuclear Information System (INIS)

    White, C.L.

    1984-01-01

    Interfacial segregation, often confined to within a few atomic distances of the interface, can strongly influence the processing and properties of metals and ceramics. The thinness of such solute-enriched regions can cause them to be particularly suitable for study using surface sensitive microanalytical techniques such as Auger electron spectroscopy (AES). The application of AES to studies of interfacial segregation in metals and ceramics is briefly reviewed, and several examples are presented. 43 references, 14 figures

  20. Positron annihilation induced Auger electron spectroscopic studies of oxide surfaces

    Science.gov (United States)

    Nadesalingam, Manori

    2005-03-01

    Defects on oxide surfaces are well known to play a key role in catalysis. TiO2, MgO, SiO2 surfaces were investigated using Time-Of-Flight Positron induced Auger Electron Spectroscopy (TOF-PAES). Previous work in bulk materials has demonstrated that positrons are particularly sensitive to charged defects. In PAES energetic electron emission results from Auger transitions initiated by annihilation of core electrons with positrons trapped in an image-potential well at the surface. Annealed samples in O2 environment show a strong Auger peak of Oxygen. The implication of these results will be discussed

  1. A coincidence study between photo- and Auger electrons

    International Nuclear Information System (INIS)

    Ricz, S.; Koever, A.; Varga, D.; Molnar, J.; Aksela, S.; Jurvansuu, M.

    2000-01-01

    Complete text of publication follows. The investigation of double differential cross sections of photon induced Auger electrons provides very sensitive method for studying the rearrangement process, especially when the angular correlation between photo- and Auger electrons is also studied. Such type of measurements could reveal a new aspect in studying the electron-electron, hole-electron and photoelectron - Auger electron interactions. It enables one to separate the overlapping Auger lines belonging to different initial holes. The traditional coincidence measurement is very time consuming and causes serious calibration problems. In order to overcome these experimental difficulties a new electron-spectrometer (ESA-22) was developed in ATOMKI, Debrecen in cooperation with the Electron spectroscopy group of University of Oulu, Finland. The analyzer consists of a spherical and a cylindrical part. It is very similar to the ESA-21 analyzer. The main differences is that the focal ring can be set different diameters thus either a series of channel detectors can be used to detect the electrons at different angles or a position sensitive channel plate can be applied for simultaneous angular recording of electrons. Furthermore the outer sphere and cylinder are cut into two parts so the spectrometer is capable to analyze two independent angularly resolved electron spectra (in the 0 deg - 180 deg region) at different energy regions, simultaneously. A special electronic control and data handling electronics and software was worked out to control the analyzer. The first results were presented in. In the last year the ESA-22 electron-spectrometer was transported to the I411 beam line of MAX-II synchrotron in Lund, Sweden. The advanced properties of the spectrometer was investigated by measuring coincidences between the photoelectrons originated from the Ar L 3 subshell and the Ar Auger electrons in the 203-207 eV energy region. Fig. 1 shows the single and the coincidence spectra

  2. X-ray induced production and yield kinetics of photo- and Auger Electrons in semiconductors

    International Nuclear Information System (INIS)

    Peregudov, V.I.; Pashaev, Eh.M.

    1991-01-01

    The paper is dedicated to theoretical and experimental analysis of the mechanism of indirect excitation of soft Auger-electrons due to atom electron ionization using Ge crystal exposed to MoK α radiation as an example. Process of generation of these Auger-electrons is considered in detail, solution of kinetic equation for electrons, as well as, experimental data proving crucial role of indirect processes in generation of soft Auger-electrons are given

  3. 3 to 15 keV Ar+ induced Auger electron emission from Si and Ar

    International Nuclear Information System (INIS)

    Kempf, J.; Kaus, G.

    1977-01-01

    Ar + induced Auger electrons from Si and Ar were investigated at bombardment energies between 3-15 keV and target currents of a few μA. The Auger electron yields were compared with secondary ion yields of Si and Ar by simultaneous SIMS-AES measurements. In the ion induced Auger spectra of Si five Auger peaks and in the Ar spectra three Auger peaks were observed. The ion induced Auger electron yield of Si and Ar were found to be strongly dependent upon the primary ion energy. 'Bulk like' and 'atomic like' Auger transitions of ion induced Auger electrons of Si were observed. (orig.) [de

  4. Back-view Auger electron spectrometer-diffractometer

    International Nuclear Information System (INIS)

    Antipov, V.G.; Bol'shunov, I.B.; Romanov, S.S.

    1990-01-01

    Design of a device on the base of quasispherical four-grid energy analyzer for recording the Auger electron spectra (AES) and observation of the patterns of slow electron diffraction (SED) on the side of an electron gun, is described. A layout of a small-sized electron gun providing for diffraction pattern recording up to the electron energies E ≅ 20 eV, is presented. At E=100 eV the gun current is ≅ 0.8 muA at electron beam diameter on a sample ≤ 1 mm. In the AES regime the gun allows one to record Auger spectra at electron energy E ≤ 3 keV, current ≅ 5 muA and electron beam diameter on a sample ≤ 0.2 mm. The maximum gun current is ≅ 25 muA for an increased beam diameter. Exapmles illustrating the device operation in AES and SED regimes, are presented

  5. Photoelectron spectroscopy and Auger electron spectroscopy of solids and surfaces

    International Nuclear Information System (INIS)

    Kowalczyk, S.P.

    1976-01-01

    The use of photoelectron spectroscopy, primarily x-ray photoelectron spectroscopy, to obtain information on the electronic structure of a wide variety of solids (especially the bulk electronic structure of solids) is covered. Both valence band and core-level spectra, as well as a few cases of photon excited Auger electron spectroscopy, are employed in the investigations to derive information on N(E). The effect of several modulations inherent in the measured I(E)'s, such as final state band structure, cross section, and relaxation, is discussed. Examples of many-electron interactions in PES are given. Some experimental aspects of PES and AES studies are given with emphasis on sample preparation techniques. Multiple splitting of core levels is examined using the Mn levels in MnF 2 as a detailed case study. Core level splittings in transition metals, rare earth metals, transition metal halides and several alloys are also reported. The application of PES to the study of the chemical bond in some crystalline semiconductors and insulators, A/sup N/B/sup 8-N/ and A/sup N/B/sup 10-N/ compounds is treated, and a spectroscopic scale of ionicity for these compounds is developed from the measured ''s-band'' splitting in the valence band density of states

  6. Relationship between chromatin structure and sensitivity to molecularly targeted auger electron radiation therapy.

    NARCIS (Netherlands)

    Terry, S.Y.A.; Vallis, K.A.

    2012-01-01

    PURPOSE: The open structure of euchromatin renders it susceptible to DNA damage by ionizing radiation (IR) compared with compact heterochromatin. The effect of chromatin configuration on the efficacy of Auger electron radiotherapy was investigated. METHODS AND MATERIALS: Chromatin structure was

  7. Local radiolytic effectiveness of Auger electrons of iodine-125 in benzene-iodine solutions

    International Nuclear Information System (INIS)

    Uenak, P.; Uenak, T.

    1987-01-01

    High radiotoxicity of iodine-125 has been mainly attributed to the local radiolytic effects of Auger electrons on biological systems. In the present study, experimental and theoretical results are compared. The agreement between the experimental and theoretical results explains that the energy absorption of iodine aggregates has an important role in the radiolytic effectiveness of Auger electrons and iodine-125 in benzene-iodine solutions. (author) 18 refs.; 3 figs

  8. Ne, Ar, Fe, and Cu Auger-electron production at National Synchrotron Light Source

    International Nuclear Information System (INIS)

    Lee, D.H.; Johnson, B.M.; Jones, K.W.; Guardala, N.A.; Price, J.L.; Stumborg, M.F.; Glass, G.A.

    1992-01-01

    Energetic K and L Auger electrons produced by focussed, filtered, broad-band synchrotron radiation have been measured at the x-ray ring of the National Synchrotron Light Source (NSLS). The x-ray beam was used to study inner-shell photoionization of Ne and Ar gas and Fe and Cu solid film targets. The Auger electrons were analyzed by means of a semi-hemispherical electrostatic electron spectrometer at the energy resolution of ∼ 3 %. The electrons were detected at both 90 degree and 0 degree with respect to the photon beam direction. Broad distributions of the inner-shell photoelectrons were also observed, reflecting the incoming photon flux distribution. The Fe and Cu K Auger electron spectra were found to be very similar to the Ar K Auger electron spectra. This was expected, since deep inner-shell Auger processes are not affected by the outer valence electrons. Above 3 keV in electron energy, there have been few previous Auger electron measurements. 2 figs., 13 refs

  9. Application of a digital data acquisition system for time of flight Positron annihilation-induced Auger Electron Spectroscopy

    Science.gov (United States)

    Gladen, R. W.; Chirayath, V. A.; McDonald, A. D.; Fairchild, A. J.; Chrysler, M. D.; Imam, S. K.; Koymen, A. R.; Weiss, A. H.

    We describe herein a digital data acquisition system for a time-of-flight Positron annihilation-induced Auger Electron Spectrometer. This data acquisition system consists of a high-speed digitizer collecting signals induced by Auger electrons and annihilation gammas in a multi-channel plate electron detector and a BaF2 gamma detector, respectively. The time intervals between these two signals is used to determine the times of flight of the Auger electrons, which are analyzed by algorithms based on traditional nuclear electronics methods. Ultimately, this digital data acquisition system will be expanded to incorporate the first coincidence measurements of Auger electron and annihilation gamma energies.

  10. Coincident Auger electron and recoil ion momentum spectroscopy for low-energy ion-atom collisions

    International Nuclear Information System (INIS)

    Laurent, G.; Tarisien, M.; Flechard, X.; Jardin, P.; Guillaume, L.; Sobocinski, P.; Adoui, L.; Bordenave-Montesquieu, A.; Bordenave-Montesquieu, D.; Chesnel, J.-Y.; Fremont, F.; Hennecart, D.; Lienard, E.; Maunoury, L.; Moretto-Capelle, P.; Cassimi, A.

    2003-01-01

    The recoil ion momentum spectroscopy (RIMS) method combined with the detection of Auger electrons has been used successfully to analyse double electron capture following O 6+ + He collisions at low impact velocities. Although RIMS and Auger spectroscopies are known to be efficient tools to obtain details on the primary processes occurring during the collision, the conjunction of both techniques provides new insights on the electron capture process. In the present experiment, triple coincidence detection of the scattered projectile, the target recoil ion and the Auger electron allows for a precise identification of the doubly excited states O 4+ (1s 2 nln ' l ' ) populated after double electron-capture events

  11. Measurement of Auger electron energies and intensities from muonic transitions in silver

    International Nuclear Information System (INIS)

    Callies, R.; Daniel, H.; Egidy, T. von; Hagn, H.; Hartmann, F.J.; Neumann, W.

    1983-01-01

    There is now general agreement that Coulomb capture of mesonic particles and deexcitation of the formed exotic atom must be accompanied by Auger electron emission. Auger electrons from a thin silver foil were counted by Si-pn-junction detectors with an extraordinarily thin dead layer. Lines could be resolved and intensity ratios determined. Two types of experiments were performed simultaneously, (I) with the slow-muon telescope in coincidence with any e - detector of the array and (II) as above but with an additional Ag X-ray coincidence from a Ge(Li) detector placed close to the target. (Auth.)

  12. Correlation of the Auger electrons direction of movement with the internal electron conversion direction of movement

    International Nuclear Information System (INIS)

    Mitrokhovich, N.F.; Kupryashkin, V.T.; Sidorenko, L.P.

    2013-01-01

    On installation of coincidences of γ-quanta with electrons and with law energy electrons about zero area the spatial correlation of the direction emitting Auger-electrons and electron of internal conversion was investigated at the 152 Eu decay. Auger-electrons were registered on e 0 -electrons of the secondary electron emission (γ e IC e 0 -coincidences). It was established, that Auger-electrons of M-series, as well as electrons 'shake-off' at β-decay and internal conversion, are strongly correlated at the direction of movement with the direction of movement of basic particle (β -particle, conversion electron), moving together mainly in the forward hemisphere. The intensity of correlated M-Auger radiation in range energy 1000 - 1700 eV is equal to intensity of correlated radiation 'shake-off' electron from internal conversion in this range. The assumption, that the presence of spatial correlating Auger-electron and conversion electron caused by cur-rent components of electron-electron interaction of particles in the final state is made

  13. Auger-electron spectroscopy investigation of thin Ag-As-S-Se films

    International Nuclear Information System (INIS)

    Todorov, R; Spasov, G; Petkov, K; Tasseva, J

    2010-01-01

    The photoinduced changes in the refractive index and optical band-gap of thin As 32 S 34 Se 34 films photodoped with silver were studied using spectrophotometric methods. The compositional profile of the films was revealed by means of Auger-electron spectroscopy.

  14. Auger-electron spectroscopy investigation of thin Ag-As-S-Se films

    Energy Technology Data Exchange (ETDEWEB)

    Todorov, R; Spasov, G; Petkov, K; Tasseva, J, E-mail: jordanka@clf.bas.b [Acad. J. Malinowski Central Laboratory of Photoprocesses, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 109, 1113 Sofia (Bulgaria)

    2010-04-01

    The photoinduced changes in the refractive index and optical band-gap of thin As{sub 32}S{sub 34}Se{sub 34} films photodoped with silver were studied using spectrophotometric methods. The compositional profile of the films was revealed by means of Auger-electron spectroscopy.

  15. Microprocessor system for data acquisition processing and display for Auger electrons spectrometer

    International Nuclear Information System (INIS)

    Pawlowski, Z.; Cudny, W.; Hildebrandt, S.; Marzec, J.; Walentek, J.; Zaremba, K.

    1984-01-01

    Data acquisition system for Auger electron spectrometry is developed. The system is used for chemical and structural analysis of materials and consists of a cylindrical mirror analyzer being a measuring spectrometer device, CAMAC unit and control unit. The control unit comprises a microcomputer based on INTEL 8080 microprocessor and display

  16. Estrogen

    Science.gov (United States)

    ... menopause ('change of life', the end of monthly menstrual periods). Some brands of estrogen are also used ... you.Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

  17. Positron annihilation induced Auger electron spectroscopy and its implementation at accelerator based low energy positron factories

    International Nuclear Information System (INIS)

    Weiss, A.; Koeymen, A.R.; Mehl, D.; Lee, K.H.; Yang Gimo; Jensen, K.

    1991-01-01

    Positron annihilation induced auger electron spectroscopy (PAES) makes use of a beam of low energy positrons to excite Auger transitions by annihilating core electrons. The large secondary electron background usually present in Auger spectra can be eliminated by setting the positron beam energy well below the Auger electron energy. This allows true Auger lineshapes to be obtained. Further, because the positron is localized just outside the surface before it annihilates, PAES is extremely sensitive to the topmost atomic layer. Recent PAES results obtained at the University of Texas at Arlington will be presented. In addition, the use of high resolution energy analyzers with multichannel particle detection schemes to prevent problems due to the high data rates associated with accelerator based positron beams will be discussed. (orig.)

  18. Coincident Auger electron and recoil ion momentum spectroscopy for low-energy ion-atom collisions

    Energy Technology Data Exchange (ETDEWEB)

    Laurent, G. E-mail: glaurent@ganil.fr; Tarisien, M.; Flechard, X.; Jardin, P.; Guillaume, L.; Sobocinski, P.; Adoui, L.; Bordenave-Montesquieu, A.; Bordenave-Montesquieu, D.; Chesnel, J.-Y.; Fremont, F.; Hennecart, D.; Lienard, E.; Maunoury, L.; Moretto-Capelle, P.; Cassimi, A

    2003-05-01

    The recoil ion momentum spectroscopy (RIMS) method combined with the detection of Auger electrons has been used successfully to analyse double electron capture following O{sup 6+} + He collisions at low impact velocities. Although RIMS and Auger spectroscopies are known to be efficient tools to obtain details on the primary processes occurring during the collision, the conjunction of both techniques provides new insights on the electron capture process. In the present experiment, triple coincidence detection of the scattered projectile, the target recoil ion and the Auger electron allows for a precise identification of the doubly excited states O{sup 4+} (1s{sup 2}nln{sup '}l{sup '}) populated after double electron-capture events.

  19. Production of the Ne Auger electrons by Ne/sup +/ bombardment of Mg and Al surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Ferrante, J; Pepper, S V [National Aeronautics and Space Administration, Cleveland, Ohio (USA). Lewis Research Center

    1976-07-01

    The authors have bombarded Mg and Al surfaces with Ne/sup +/ ions and in this letter present evidence for the production of an inner shell vacancy in the Ne by the asymmetric Ne-Mg and Ne-Al collision. In addition, autoionization states of neutral Ne have been observed. These states are to be distinguished from the more usual case in Auger electron spectroscopy of de-excitation of an ion with a core vacancy.

  20. Determination of local absolute detection efficiency of a ceratron with 55Fe Auger electrons

    International Nuclear Information System (INIS)

    Mori, C.; Sugiyama, T.; Watanabe, T.

    1983-01-01

    The local absolute detection efficiency of a Ceratron (channel electron multiplier made of ceramics) was determined with collimated Mn K Auger electrons ( 5 keV) emitted from 55 Fe as a function of electron incident position and applied voltage. The local efficiency at the channel inlet did not depend so much on the applied voltage. The efficiency at the funnel increased with the applied voltage, while it was always lower than that at the channel inlet. (orig.)

  1. Application of positron annihilation induced auger electron spectroscopy to the study of surface chemistry

    International Nuclear Information System (INIS)

    Weiss, A.H.; Yang, G.; Nangia, A.; Kim, J.H.; Fazleev, N.G.

    1996-01-01

    Positron annihilation induced Auger Electron Spectroscopy (PAES), makes use a beam of low energy positrons to excite Auger transitions by annihilating core electrons. This novel mechanism provides PAES with a number of unique features which distinguishes it from other methods of surface analysis. In PAES the very large collisionally induced secondary electron background which is present under the low energy Auger peaks using conventional techniques can be eliminated by using a positron beam whose energy is below the range of Auger electron energies. In addition, PAES is more surface selective than conventional Auger Spectroscopy because the PAES signal originates almost exclusively from the topmost atomic layer due to the fact that the positrons annihilating with the core electrons are trapped in an image correlation well just outside the surface. In this paper, recent applications of Positron Annihilation Induced Auger Electron Spectroscopy (PAES) to the study of surface structure and surface chemistry will be discussed including studies of the growth, alloying and inter-diffusion of ultrathin layers of metals, metals on semiconductors, and semiconductors on semiconductors. In addition, the possibilities for future application of PAES to the study of catalysis and surface chemistry will be outlined. (author)

  2. Novel time-of-flight spectrometer for the analysis of positron annihilation induced Auger electrons

    International Nuclear Information System (INIS)

    Hugenschmidt, Christoph; Legl, Stefan

    2006-01-01

    Positron annihilation induced Auger-electron spectroscopy (PAES) has several advantages over conventional Auger-electron spectroscopy such as extremely high surface sensitivity and outstanding signal-to-noise ratio at the Auger-transition energy. In order to benefit from these prominent features a low-energy positron beam of high intensity is required for surface sensitive PAES studies. In addition, an electron energy analyzer is required, which efficiently detects the Auger electrons with acceptable energy resolution. For this reason a novel time-of-flight (TOF) spectrometer has been developed at the intense positron source NEPOMUC that allows PAES studies within short measurement time. This TOF-PAES setup combines a trochoidal filter and a flight tube in a Faraday cage in order to achieve an improved energy resolution of about 1 eV at high electron energies up to E≅1000 eV. The electron flight time is the time between the annihilation radiation at the sample and when the electron hits a microchannel plate detector at the end of the flight tube

  3. Electron beam effects in auger electron spectroscopy and scanning electron microscopy

    International Nuclear Information System (INIS)

    Fontaine, J.M.; Duraud, J.P.; Le Gressus, C.

    1979-01-01

    Electron beam effects on Si(100) and 5% Fe/Cr alloy samples have been studied by measurements of the secondary electron yield delta, determination of the surface composition by Auger electron spectroscopy and imaging with scanning electron microscopy. Variations of delta as a function of the accelerating voltage Esub(p) (0.5 -9 Torr has no effect on technological samples covered with their reaction layers; the sensitivities to the beam depend rather on the earlier mechanical, thermal and chemical treatment of the surfaces. (author)

  4. A new route to nanoscale tomographic chemical analysis: Focused ion beam-induced auger electron spectrosocpy

    Science.gov (United States)

    Parvaneh, Hamed

    This research project is aimed to study the application of ion-induced Auger electron spectroscopy (IAES) in combination with the characteristics of focused ion beam (FIB) microscopy for performing chemical spectroscopy and further evaluate its potential for 3-dimensional chemical tomography applications. The mechanism for generation of Auger electrons by bombarding ions is very different from its electron induced counterpart. In the conventional electron-induced Auger electron spectroscopy (EAES), an electron beam with energy typically in the range 1-10kV is used to excite inner-shell (core) electrons of the solid. An electron from a higher electron energy state then de-excites to fill the hole and the extra energy is then transferred to either another electron, i.e. the Auger electron, or generation of an X-ray (photon). In both cases the emitting particles have charac-teristic energies and could be used to identify the excited target atoms. In IAES, however, large excitation cross sections can occur by promotion of in-ner shell electrons through crossing of molecular orbitals. Originally such phenomenological excitation processes were first proposed [3] for bi-particle gas phase collision systems to explain the generation of inner shell vacancies in violent collisions. In addition to excitation of incident or target atoms, due to a much heavier mass of ions compared to electrons, there would also be a substantial momentum transfer from the incident to the target atoms. This may cause the excited target atom to recoil from the lattice site or alternatively sputter off the surface with the possibility of de-excitation while the atom is either in motion in the matrix or traveling in vacuum. As a result, one could expect differences between the spectra induced by incident electrons and ions and interpretation of the IAE spectra requires separate consideration of both excitation and decay processes. In the first stage of the project, a state-of-the-art mass

  5. Characterization of a Fe inclusion in beryllium-matrix using auger electron spectroscopy

    International Nuclear Information System (INIS)

    Arkusk, R.; Moreno, D.; Simca, F.; Yeheskel, O.; Utzmoni, U.

    1991-04-01

    The auger electron spectroscopy techniques was employed to investigate the nature of an inclusion that had been revealed by radiography in a beryllium body produced by the hot isostatic press technique. The investigation's are that the inclusion is composed of several different iron-beryllium intermetallic compounds (BeFe 3 , BeFe 5 , Be 7 Fe). The conclusion drawn is that iron metal impurity was imbedded in the Be powder and that interdiffusion under the process's conditions gave rise to the enlarged inclusion. (author)

  6. Surface analysis of Al alloys with X-ray photoelectron and Auger electron spectroscopies

    International Nuclear Information System (INIS)

    Sakairi, Masatoshi; Suzuki, Keita; Sasaki, Ryo

    2015-01-01

    In this paper, X-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES) were applied to investigate passive films formed on aluminum alloy in 0.5 kmol m -3 H 3 BO 3 /0.05 kmol m -3 Na 2 B 4 O 7 with different metal cations. The metal cation is classified by metal cation hardness, X, which are calculated based on the concept of hard and soft acids and bases (HSAB) of the acid and base in Lewis's rule. From XPS analysis, the metal cations with X > 4 were incorporated in passive films. The area-selected surface analysis of AES was also introduced. (author)

  7. Use of analytical electron microscopy and auger electron spectroscopy for evaluating materials

    International Nuclear Information System (INIS)

    Jones, R.H.; Bruemmer, S.M.; Thomas, M.T.; Baer, D.R.

    1982-11-01

    Analytical electron microscopy (AEM) can be used to characterize the microstructure and microchemistry of materials over dimensions less than 10 nm while Auger electron spectroscopy (AES) can be used to characterize the chemical composition of surfaces and interfaces to a depth of less than 1 nm. Frequently, the information gained from both instruments can be coupled to give new insight into the behavior of materials. Examples of the use of AEM and AES to characterize segregation, sensitization and radiation damage are presented. A short description of the AEM and AES techniques are given

  8. Summary Report of Consultants' Meeting on Auger Electron Emission Data Needs for Medical Applications

    International Nuclear Information System (INIS)

    Noy, Roberto Capote; Chung, Hyun Kyung; Bartschat, Klaus; Dong, Chenzhong; Jonsson, Per; Kibedi, Tibor; Kondev, Filip G.; Nikjoo, Hooshang; Palffy, Adriana

    2013-11-01

    A summary is given of a Consultants' Meeting on 'Auger Electron Emission Data Needs for Medical Applications'. Participants assessed and reviewed detailed atomic and nuclear data needs for a number of Auger emitters deemed as potentially suitable for applications in nuclear medicine and radiotherapy. Technical discussions are described in this report, along with recommendations for future work, along with recommendations for future work. Presentations by the consultants at the meeting are available at http://www-nds.iaea.org/index-meeting-crp/CM-Auger-2013/. (author)

  9. IMPURITY SEGREGATION OF STAINLESS STEEL STUDIED BY ATOM-PROBE AND AUGER ELECTRON SPECTROSCOPY

    OpenAIRE

    Koguchi , Y.; Takahashi , K.; Ishikawa , Y.

    1987-01-01

    The surface compositions of type 304 stainless steel heated in vacuum at 600-900°C were determined by an atom-probe and Auger electron spectroscopic analysis. In addition to enrichment and depletion of alloying elements in the surface of the stainless steel, segregation of impurity elements such as carbon, nitrogen, phosphorus and sulfur is known to occur. In this paper the atom-probe was used to measure the impurity segregation in the grains as well as in the grain boundary while the AES was...

  10. Angular distribution of Auger electrons due to 3d-shell ionization of krypton

    Science.gov (United States)

    Omidvar, K.

    1977-01-01

    Cross sections for electron impact ionization of krypton due to ejection of a 3rd shell electron have been calculated using screened hydrogenic and Hartree-Slater wave functions for target atom. While the total ionization cross sections in the two approximations are within 10% of each other, the Auger electron angular distribution, related to cross sections for specific magnetic quantum numbers of the 3rd electrons, is widely different in the two approximations. The angular distribution due to Hartree-Slater approximation is in excellent agreement with measurement. The physical reason for the discrepancies in the two approximations is explained.

  11. Angular distribution of Auger electrons due to 3d-shell impact ionization of krypton

    Science.gov (United States)

    Omidvar, K.

    1977-01-01

    Cross sections for electron impact ionization of krypton due to ejection of a 3d-shell electron have been calculated using screened hydrogenic and Hartree-Slater wavefunctions for the target atom. While the total ionization cross sections in the two approximations are within 10% of each other, the Auger electron angular distribution, related to cross sections for specific magnetic quantum numbers of the 3d electrons, are widely different in the two approximations. The angular distribution due to the Hartree-Slater approximation is in excellent agreement with measurement. The physical reason for the discrepancies in the two approximations is explained.

  12. Chirped Auger electron emission due to field-assisted post-collision interaction

    Directory of Open Access Journals (Sweden)

    Bonitz M.

    2013-03-01

    Full Text Available We have investigated the Auger decay in the temporal domain by applying a terahertz streaking light field. Xenon and krypton atoms were studied by implementing the free-electron laser in Hamburg (FLASH as well as a source of high-order harmonic radiation combined with terahertz pulses from an optical rectification source. The observed linewidth asymmetries in the streaked spectra suggest a chirped Auger electron emission which is understood in terms of field-assisted post-collision interaction. The experimentally obtained results agree well with model calculations.

  13. Auger electron spectroscopy study on interaction between aluminum thin layers and uranium substrate

    International Nuclear Information System (INIS)

    Zhou Wei; Liu Kezhao; Yang Jiangrong; Xiao Hong; Jiang Chunli; Lu Lei

    2005-01-01

    Aluminum thin layers on uranium were prepared by sputter deposition at room temperature in ultra high vacuum analysis chamber. Interaction between U and Al, and growth mode were investigated by Auger electron spectroscopy (AES) and electron energy loss spectroscopy (EELS). It is shown that Al thin film growth follows the volmer-weber (VW) mode. At room temperature, Al and U interact with each other, resulting in interdiffusion action and formation of U-Al alloys at U/Al interface. Annealing promotes interaction and interdiffusion between U and Al, and UAl x maybe formed at interface. (authors)

  14. Methods for Determining Metal Uptake in Cellular DNA for Auger Electron Therapy

    International Nuclear Information System (INIS)

    Seror, V.; Novick, S.; Weiner, E.; Laster, B.; Hambright, P.

    2004-01-01

    Stable indium-labeled tetra(4-N-methylpyridyl)porphyrin [InTMPyP(4)] was evaluated as a carrier of a high Z atom, indium (In), into tumor cell DNA for its subsequent activation by radiation in a proposed radiotherapeutic technique, Auger Electron Therapy (AET). Porphyrins with metals can bind to DNA and are useful vehicles for transporting the indium to the DNA of the tumor. AET combines the use of a metalloporphyrin with a stable high Z atom, such as indium, and photons emitted from radioactive brachytherapy seeds, such as iodine-125, to increase the radiation dose in the DNA of the tumor by generating a photoelectric effect in the K absorption edge of the indium (In) atom. This results in the emission of cascading Auger electrons that act as high LET radiation and thus impart significant non-reparable damage to the tumor compared to the radiation alone. The K absorption edge of In is 27.9 keV and the average photon energy of the iodine-125 seeds is ∼ 28 keV

  15. A new calculational method to assess the therapeutic potential of Auger electron emission

    International Nuclear Information System (INIS)

    Humm, J.L.; Charlton, D.E.

    1989-01-01

    This paper discusses a new computer code to estimate the efficacy of Auger electron sources in cancer therapy. Auger electron emission accompanies the decay of many radionuclides already commonly used in nuclear medicine, for example; 99m Tc and 201 Tl. The range of these electrons is in general sub-cellular, therefore, the toxicity of the source depends on the site of decay relative to the genetic material of the cell. Electron track structure methods have been used which enable the study of energy deposition from Auger sources down to the Angstrom level. A figure for the minimum energy required per single strand break is obtained by fitting our energy deposition calculations for 125 I decays in a model of the DNA to experimental data on break lengths from 125 I labeled plasmid fragments. This method is used to investigate the efficiency of double strand break production by other Auger sources which have potential value for therapy. The high RBE of Auger sources depends critically on the distance between the source and target material. The application of Auger emitters for therapy may necessitate a carrier molecule that can append the source to the DNA. Many DNA localizing agents are known in the field of chemotherapy, some of which could be carrier molecules for Auger sources; the halogenated thymidine precursors are under scrutiny in this field. The activation of Auger cascades in situ by high energy, collimated X ray and neutron beams is also assessed

  16. Depth-selective X-ray absorption spectroscopy by detection of energy-loss Auger electrons

    Energy Technology Data Exchange (ETDEWEB)

    Isomura, Noritake, E-mail: isomura@mosk.tytlabs.co.jp [Toyota Central R& D Labs., Inc., 41-1 Yokomichi, Nagakute, Aichi 480-1192 (Japan); Soejima, Narumasa; Iwasaki, Shiro [Toyota Central R& D Labs., Inc., 41-1 Yokomichi, Nagakute, Aichi 480-1192 (Japan); Nomoto, Toyokazu; Murai, Takaaki [Aichi Synchrotron Radiation Center (AichiSR), 250-3 Minamiyamaguchi-cho, Seto, Aichi 489-0965 (Japan); Kimoto, Yasuji [Toyota Central R& D Labs., Inc., 41-1 Yokomichi, Nagakute, Aichi 480-1192 (Japan)

    2015-11-15

    Graphical abstract: - Highlights: • A unique XAS method is proposed for depth profiling of chemical states. • PEY mode detecting energy-loss electrons enables a variation in the probe depth. • Si K-edge XAS spectra of the Si{sub 3}N{sub 4}/SiO{sub 2}/Si multilayer films have been investigated. • Deeper information was obtained in the spectra measured at larger energy loss. • Probe depth could be changed by the selection of the energy of detected electrons. - Abstract: A unique X-ray absorption spectroscopy (XAS) method is proposed for depth profiling of chemical states in material surfaces. Partial electron yield mode detecting energy-loss Auger electrons, called the inelastic electron yield (IEY) mode, enables a variation in the probe depth. As an example, Si K-edge XAS spectra for a well-defined multilayer sample (Si{sub 3}N{sub 4}/SiO{sub 2}/Si) have been investigated using this method at various kinetic energies. We found that the peaks assigned to the layers from the top layer to the substrate appeared in the spectra in the order of increasing energy loss relative to the Auger electrons. Thus, the probe depth can be changed by the selection of the kinetic energy of the energy loss electrons in IEY-XAS.

  17. Depth-selective X-ray absorption spectroscopy by detection of energy-loss Auger electrons

    International Nuclear Information System (INIS)

    Isomura, Noritake; Soejima, Narumasa; Iwasaki, Shiro; Nomoto, Toyokazu; Murai, Takaaki; Kimoto, Yasuji

    2015-01-01

    Graphical abstract: - Highlights: • A unique XAS method is proposed for depth profiling of chemical states. • PEY mode detecting energy-loss electrons enables a variation in the probe depth. • Si K-edge XAS spectra of the Si_3N_4/SiO_2/Si multilayer films have been investigated. • Deeper information was obtained in the spectra measured at larger energy loss. • Probe depth could be changed by the selection of the energy of detected electrons. - Abstract: A unique X-ray absorption spectroscopy (XAS) method is proposed for depth profiling of chemical states in material surfaces. Partial electron yield mode detecting energy-loss Auger electrons, called the inelastic electron yield (IEY) mode, enables a variation in the probe depth. As an example, Si K-edge XAS spectra for a well-defined multilayer sample (Si_3N_4/SiO_2/Si) have been investigated using this method at various kinetic energies. We found that the peaks assigned to the layers from the top layer to the substrate appeared in the spectra in the order of increasing energy loss relative to the Auger electrons. Thus, the probe depth can be changed by the selection of the kinetic energy of the energy loss electrons in IEY-XAS.

  18. The characterisation of non-evaporable getters by Auger electron spectroscopy Analytical potential and artefacts

    CERN Document Server

    Scheuerlein, C; Taborelli, M

    2002-01-01

    The surfaces of getter materials are particularly difficult to analyse because of their high chemical reactivity. The results obtained can be strongly influenced by the experimental set-up and procedures. In this paper the experimental influence on the Auger electron spectroscopy results is discussed, based on the measurements of more than 100 different non-evaporable getter (NEG) materials. There are four typical changes in the Auger electron spectra when a NEG becomes activated. The oxygen peak intensity decreases, the shape of the metal peaks changes, the carbon peak shape changes shape and intensity and a chlorine peak occurs. All these changes are affected by instrumental artefacts. The Zr-MNV peak shape changes occurring during the reduction of ZrO2 are well suited to determine the onset of NEG activation, while the slope with which the O-KLL peak intensity decreases in a certain temperature range is a better criterion for the determination of the temperature at which activation is complete. The O-KLL i...

  19. Photoelectron-Auger electron coincidence spectroscopy of free molecules: New experiments

    International Nuclear Information System (INIS)

    Ulrich, Volker; Barth, Silko; Lischke, Toralf; Joshi, Sanjeev; Arion, Tiberiu; Mucke, Melanie; Foerstel, Marko; Bradshaw, Alex M.; Hergenhahn, Uwe

    2011-01-01

    Photoelectron-Auger electron coincidence spectroscopy probes the dicationic states produced by Auger decay following the photoionization of core or inner valence levels in atoms, molecules or clusters. Moreover, the technique provides valuable insight into the dynamics of core hole decay. This paper serves the dual purpose of demonstrating the additional information obtained by this technique compared to Auger spectroscopy alone as well as of describing the new IPP/FHI apparatus at the BESSY II synchrotron radiation source. The distinguishing feature of the latter is the capability to record both the photoelectron and Auger electron with good energy and angle resolution, for which purpose a large hemispherical electrostatic analyser is combined with several linear time-of-flight spectrometers. New results are reported for the K-shell photoionization of oxygen (O 2 ) and the subsequent KVV Auger decay. Calculations in the literature for non-coincident O 2 Auger spectra are found to be in moderately good agreement with the new data.

  20. X-ray fluorescence/Auger-electron coincidence spectroscopy of vacancy cascades in atomic argon

    International Nuclear Information System (INIS)

    Arp, U.

    1996-01-01

    Argon L 2.3 -M 2.3 M 2.3 Auger-electron spectra were measured in coincidence with Kα fluorescent x-rays in studies of Ar K-shell vacancy decays at several photon energies above the K-threshold and on the 1s-4p resonance in atomic argon. The complex spectra recorded by conventional electron spectroscopy are greatly simplified when recorded in coincidence with fluorescent x-rays, allowing a more detailed analysis of the vacancy cascade process. The resulting coincidence spectra are compared with Hartree-Fock calculations which include shake-up transitions in the resonant case. Small energy shifts of the coincidence electron spectra are attributed to post-collision interaction with 1s photoelectrons

  1. Surface analysis of WC--Co composite materials (2) Quantitative Auger electron spectrometry

    International Nuclear Information System (INIS)

    Tongson, L.L.; Biggers, J.V.; Dayton, G.O.; Bind, J.M.; Knox, B.E.

    1978-01-01

    The unique sensitivity of Auger electron spectrometry (AES) to combined carbon has been exploited in measuring the surface compositions of hot-pressed, conventionally sintered and mixed powders of WC--Co composite materials. AES sensitivity factors for tungsten and carbon (in WC) relative to cobalt were determined. The concentrations of the major elements in hot-pressed samples measured with AES using the relative sensitivity method were compared to those obtained independently by electron microprobe (EMP) and x-ray fluorescence (XRF) techniques. Corollary studies using ion scattering spectrometry (ISS) showed the absence of (1) matrix effects in the AES measurements, (2) preferential sputtering during ion bombardment, and (3) deposition of the easier-to-sputter component (cobalt) onto WC

  2. Auger electron spectroscopy investigation of metallic fusible links in programmable read-only memories

    International Nuclear Information System (INIS)

    Morgan, A.E.; Quackenbush, T.R.; Lim, S.C.P.

    1983-01-01

    The composition of Ni-Cr, Ti-W and Ti-W-N thin film fuses as used in bipolar programmable read-only memories was studied using Auger electron spectroscopy. Measurements were performed on both intact and blown fuses in actual devices, and also on thin film samples processed so as to duplicate device fabrication. Topics of interest were (a) selection of film deposition technique, (b) minimization of contact resistance to aluminum, (c) promotion of good adhesion to SiO 2 , (d) avoidance of chemical attack during device production, (e) fuse corrosion in the finished product and (f) the fusing mechanism during device programming. The results are used to compare and contrast the behavior of the different types of fuses. From these studies, it appears that Ni-Cr could be beneficially replaced as the fuse material by Ti-W or Ti-W-N. (Auth.)

  3. Atomic and molecular photoelectron and Auger-electron-spectroscopy studies using synchrotron radiation

    International Nuclear Information System (INIS)

    Southworth, S.H.

    1982-01-01

    Electron spectroscopy, combined with synchrotron radiation, was used to measure the angular distributions of photoelectrons and Auger electrons from atoms and molecules as functions of photon energy. The branching ratios and partial cross sections were also measured in certain cases. By comparison with theoretical calculations, the experimental results are interpreted in terms of the characteristic electronic structure and ionization dynamics of the atomic or molecular sample. The time structure of the synchrotron radiation source was used to record time-of-flight (TOF) spectra of the ejected electrons. The double-angle-TOF method for the measurement of photoelectron angular distributions is discussed. This technique offers the advantages of increased electron collection efficiency and the elimination of certain systematic errors. An electron spectroscopy study of inner-shell photoexcitation and ionization of Xe, photoelectron angular distributions from H 2 and D 2 , and photoionization cross sections and photoelectron asymmetries of the valence orbitals of NO are reported

  4. Angular Correlation between Photoelectrons and Auger Electrons from K-Shell Ionization of Neon

    International Nuclear Information System (INIS)

    Landers, A. L.; Robicheaux, F.; Bhandary, A.; Jahnke, T.; Schoeffler, M.; Titze, J.; Akoury, D.; Doerner, R.; Osipov, T.; Lee, S. Y.; Adaniya, H.; Hertlein, M.; Weber, Th.; Prior, M. H.; Belkacem, A.; Ranitovic, P.; Bocharova, I.; Cocke, C. L.

    2009-01-01

    We have used cold target recoil ion momentum spectroscopy to study the continuum correlation between the photoelectron of core-photoionized neon and the subsequent Auger electron. We observe a strong angular correlation between the two electrons. Classical trajectory Monte Carlo calculations agree quite well with the photoelectron energy distribution that is shifted due to the potential change associated with Auger decay. However, a striking discrepancy results in the distribution of the relative angle between Auger and photoelectron. The classical model predicts a shift in photoelectron flux away from the Auger emission direction, and the data strikingly reveal that the flux is lost rather than diverted, indicating that the two-step interpretation of photoionization followed by Auger emission is insufficient to fully describe the core-photoionization process.

  5. Study of surface segregation of Si on palladium silicide using Auger electron spectroscopy

    International Nuclear Information System (INIS)

    Abhaya, S; Amarendra, G; Gopalan, Padma; Reddy, G L N; Saroja, S

    2004-01-01

    The transformation of Pd/Si to Pd 2 Si/Si is studied using Auger electron spectroscopy over a wide temperature range of 370-1020 K. The Pd film gets totally converted to Pd 2 Si upon annealing at 520 K, and beyond 570 K, Si starts segregating on the surface of silicide. It is found that the presence of surface oxygen influences the segregation of Si. The time evolution study of Si segregation reveals that segregation kinetics is very fast and the segregated Si concentration increases as the temperature is increased. Scanning electron microscopy measurements show that Pd 2 Si is formed in the form of islands, which grow as the annealing temperature is increased

  6. X-ray photoelectron and x-ray-induced Auger electron spectroscopic data, 1

    International Nuclear Information System (INIS)

    Baba, Yuji; Sasaki, T.A.

    1984-02-01

    The intrinsic data of the X-ray photoelectron spectra (XPS) and X-ray-induced Auger electron spectra (XAES) for 3d transition-metals and related oxides were presented. The clean surfaces of the metals were obtained by two different methods ; mechanical filings and Ar + ion etchings. The oxides examined are typical compounds such as Sc 2 O 3 , TiO 2 , V 2 O 5 and NiO. The report consists of 4 wide scans, 26 core-line spectra, 10 valence-band spectra and 20 XAES spectra. The peak positions of the core-lines and the Auger lines were summarized in 8 tables together with their chemical shifts. (author)

  7. Auger-electron cascades, charge potential and microdosimetry of iodine-125

    Energy Technology Data Exchange (ETDEWEB)

    Booz, J.; Pomplun, E.; Olko, P.; Paretzke, H.G.

    1987-06-01

    This paper is a contribution to the microdosimetry of I-125. It shows microdosimetric spectra of individual and average disintegrations of I-125 for various target sizes and gives evidence for the relative contributions of energy-depositon events of low and high LET. It further presents information on the relative efficiencies of Auger-electrons and multiple charges in terms of local energy deposition, e.g. to model targets of DNA, and discusses their radiobiological implications, e.g. the microdosimetric understanding of the different efficiencies of specific and random incorporations of I-125. When I-125 is specifically incorporated into DNA, most of the energy deposition events are very large, e.g. above 40 keV/..mu..m for a simulated target volume of 20 nm diameter, regardless of the number and energy of Auger electrons emitted. Therefore it is not necessary, for the discussion of the radiobiological implications, to distinguish between different classes of disintegrations. For unspecific, homogeneous incorporation of I-125 somewhere into tissue, about 20% of the dose to critical targets of 25 nm diameter is made up by disintegrations that happen to occur within these targets. When assuming that other critical targets and target structures can be neglected, this part of the dose will be equally effective as in the case of specific incorporation of I-125 into such target models. In addition, there are the normal, low-LET radiation effects from the other, 80% large fraction of the dose. With this information, for the biological systems and end points for which a short section of the elemental chromatine fiber can be taken as the relevant critical target, it is shown that the expected D/sub 37/ value for homogeneous unspecific incorporation of I-125 can be estimated when the D/sub 37/ for specific incorporation in DNA is known.

  8. Relationship Between Chromatin Structure and Sensitivity to Molecularly Targeted Auger Electron Radiation Therapy

    International Nuclear Information System (INIS)

    Terry, Samantha Y.A.; Vallis, Katherine A.

    2012-01-01

    Purpose: The open structure of euchromatin renders it susceptible to DNA damage by ionizing radiation (IR) compared with compact heterochromatin. The effect of chromatin configuration on the efficacy of Auger electron radiotherapy was investigated. Methods and Materials: Chromatin structure was altered in MDA-MB-468 and 231-H2N human breast cancer cells by suberoylanilide hydroxamic acid (SAHA), 5-aza-2-deoxycytidine, or hypertonic treatment. The extent and duration of chromatin structural changes were evaluated using the micrococcal nuclease assay. DNA damage (γH2AX assay) and clonogenic survival were evaluated after exposure to 111 In-DTPA-hEGF, an Auger electron-emitting radiopharmaceutical, or IR. The intracellular distribution of 111 In-DTPA-hEGF after chromatin modification was investigated in cell fractionation experiments. Results: Chromatin remained condensed for up to 20 minutes after NaCl and in a relaxed state 24 hours after SAHA treatment. The number of γH2AX foci per cell was greater in MDA-MB-468 and 231-H2N cells after IR (0.5 Gy) plus SAHA (1 μM) compared with IR alone (16 ± 0.6 and 14 ± 0.3 vs. 12 ± 0.4 and 11 ± 0.2, respectively). More γH2AX foci were observed in MDA-MB-468 and 231-H2N cells exposed to 111 In-DTPA-hEGF (6 MBq/μg) plus SAHA vs. 111 In-DTPA-hEGF alone (11 ± 0.3 and 12 ± 0.7 vs. 9 ± 0.4 and 7 ± 0.3, respectively). 5-aza-2-deoxycytidine enhanced the DNA damage caused by IR and 111 In-DTPA-hEGF. Clonogenic survival was reduced in MDA-MB-468 and 231-H2N cells after IR (6 Gy) plus SAHA (1 μM) vs. IR alone (0.6% ± 0.01 and 0.3% ± 0.2 vs. 5.8% ± 0.2 and 2% ± 0.1, respectively) and after 111 In-DTPA-hEGF plus SAHA compared to 111 In-DTPA-hEGF alone (21% ± 0.4% and 19% ± 4.6 vs. 33% ± 2.3 and 32% ± 3.7). SAHA did not affect 111 In-DTPA-hEGF nuclear localization. Hypertonic treatment resulted in fewer γH2AX foci per cell after IR and 111 In-DTPA-hEGF compared to controls but did not significantly alter clonogenic

  9. Electron stimulated carbon adsorption in ultra high vacuum monitored by Auger Electron Spectroscopy (AES)

    CERN Document Server

    Scheuerlein, C

    2001-01-01

    Electron stimulated carbon adsorption at room temperature (RT) has been studied in the context of radiation induced surface modifications in the vacuum system of particle accelerators. The stimulated carbon adsorption was monitored by AES during continuous irradiation by 2.5 keV electrons and simultaneous exposure of the sample surface to CO, CO2 or CH4. The amount of adsorbed carbon was estimated by measuring the carbon Auger peak intensity as a function of the electron irradiation time. Investigated substrate materials are technical OFE copper and TiZrV non-evaporable getter (NEG) thin film coatings, which are saturated either in air or by CO exposure inside the Auger electron spectrometer. On the copper substrate electron induced carbon adsorption from gas phase CO and CO2 is below the detection limit of AES. During electron irradiation of the non-activated TiZrV getter thin films, electron stimulated carbon adsorption from gas phase molecules is detected when either CO or CO2 is injected, whereas the CH4 ...

  10. Contribution of Auger electron spectroscopy to study of mechanism of adhesive wear of valves

    International Nuclear Information System (INIS)

    Smrkovsky, E.; Koutnik, M.; Potmesilova, A.

    1987-01-01

    Briefly characterized are hypotheses describing the process of intensive adhesive wear (jamming) of materials on functional friction surfaces of valves. Two types of alloys were studied, 1Cr18Ni8Mo5Mn5Si5Nb and NiCrSiB. Auger electron spectroscopy was used in the study of the chemical composition of surface layers. The following conclusions can be made from the results of the adhesive wear measurement and the Auger spectroscopy measurement: There are oxide layers on the surfaces of the specimens which, however, can only to a certain extent affect the process of adhesive wear. Adhesive wear resistance tests using low hardness specimens show that in spite of the existence of oxide layers, friction pairs showing low surface hardness also feature low adhesive wear resistance. Following heat treatment, the surface oxide layers have practically the same chemical composition as the specimens without heat treatment. However, there adhesive wear resistance is significantly higher. (Z.M.). 3 tabs., 7 refs

  11. X-ray photoelectron and x-ray-induced auger electron spectroscopic data, 2

    International Nuclear Information System (INIS)

    Baba, Yuji; Sasaki, Teikichi

    1984-04-01

    The intrinsic data of the X-ray photoelectron spectra (XPS) and X-ray-induced Auger electron spectra (XAES) for 4d transition-metals and related oxides were obtained by means of a spherical electron spectrometer. The metallic surfaces were cleaned by two different metheds : mechanical filing and Ar + ion etching. In the case of the Ar + io n bombarded Y, Zr, and Nb metals, the binding energies of the core-lines and the kinetic energies of the Auger lines shift from those for the mechanically filed surfaces. The energy shifts were interpreted in terms of the ion-induced lattice distortion of the metal surfaces. The oxides examined are typical compounds such as Y 2 O 3 , ZrO 2 , Nb 2 O 5 , MoO 3 and RuO 2 . The data consists of 4 wide scans, 33 core-line spectra, 10 valence-band spectra and 12 XAES spectra. The peak positions of the core-lines and the Auger lines were summarized in 6 tables together with their chemical shifts. (author)

  12. Resonant Auger electron-photoion coincidence study of the fragmentation dynamics of an acrylonitrile molecule

    Energy Technology Data Exchange (ETDEWEB)

    Kooser, K; Ha, D T; Granroth, S; Itaelae, E; Nommiste, E; Kukk, E [Department of Physics, University of Turku, FIN-20014 Turku (Finland); Partanen, L; Aksela, H, E-mail: kunkoo@utu.f [Department of Physics, University of Oulu, Box 3000, FIN-90014 Oulu (Finland)

    2010-12-14

    Monochromatic synchrotron radiation was used to promote K-shell electrons of nitrogen and carbon from the cyano group (C {identical_to} N) of gaseous acrylonitrile (C{sub 2}H{sub 3}-CN) to the unoccupied antibonding {pi}*{sub C} {sub {identical_to} N} orbital. Photofragmentation of acrylonitrile molecules following selective resonant core excitations of carbon and nitrogen core electrons to the {pi}*{sub C} {sub {identical_to} N} orbital was investigated using the electron-energy-resolved photoelecton-photoion coincidence technique. The fragment ion mass spectra were recorded in coincidence with the resonant Auger electrons, emitted in the decay process of the core-excited states. Singly and triply deuterated samples were used for fragment identification. The results showed the initial core-hole localization to be of minor importance in determining the dissociation pattern of the molecular cation. The participator and spectator Auger transitions produce entirely different fragmentation patterns and the latter indicates that complex nuclear rearrangements take place. It is suggested that the calculated kinetic energy releases are caused by the existence of metastable states, which appear with the opening of the spectator Auger channels.

  13. Electron beam interactions with CO on W[100] studied by Auger electron spectroscopy

    International Nuclear Information System (INIS)

    Housley, M.; King, D.A.

    1977-01-01

    The interaction of 2500 eV electrons with carbon monoxide chemisorbed on tungsten [100] was investigated by rapid-scan Auger electron spectroscopy. When no α state was present the O and C signals from the β state of CO were invariant during electron bombardment, giving an upper limit estimate for the electron stimulated desorption cross section, Qsub(β), of 2 x 10 -21 cm 2 . With the crystal at room temperature and saturated with CO, however, electron-beam induced accumulation of carbon was observed and characterised, the rate of the process being independent of CO pressure at pressures above 2 x 10 -8 Torr. At 450 K the rate was found to be pressure dependent up to at least 6 x 10 -7 Torr. A model is proposed for the accumulation process, which is based on electron beam dissociation of α 2 -CO to form adsorbed carbon and gaseous O and the creation of new sites for further α 2 -CO adsorption; it is in quantitative agreement with the results and yields a cross section for ESD of α 2 -CO (Qsub(α 2 )=1.55 X 10 -18 cm 2 ) in clo 2 e agreement with direct measurements. (Auth.)

  14. Detecting Fermi-level shifts by Auger electron spectroscopy in Si and GaAs

    Science.gov (United States)

    Debehets, J.; Homm, P.; Menghini, M.; Chambers, S. A.; Marchiori, C.; Heyns, M.; Locquet, J. P.; Seo, J. W.

    2018-05-01

    In this paper, changes in surface Fermi-level of Si and GaAs, caused by doping and cleaning, are investigated by Auger electron spectroscopy. Based on the Auger voltage contrast, we compared the Auger transition peak energy but with higher accuracy by using a more accurate analyzer and an improved peak position determination method. For silicon, a peak shift as large as 0.46 eV was detected when comparing a cleaned p-type and n-type wafer, which corresponds rather well with the theoretical difference in Fermi-levels. If no cleaning was applied, the peak position did not differ significantly for both wafer types, indicating Fermi-level pinning in the band gap. For GaAs, peak shifts were detected after cleaning with HF and (NH4)2S-solutions in an inert atmosphere (N2-gas). Although the (NH4)2S-cleaning in N2 is very efficient in removing the oxygen from the surface, the observed Ga- and As-peak shifts are smaller than those obtained after the HF-cleaning. It is shown that the magnitude of the shift is related to the surface composition. After Si-deposition on the (NH4)2S-cleaned surface, the Fermi-level shifts back to a similar position as observed for an as-received wafer, indicating that this combination is not successful in unpinning the Fermi-level of GaAs.

  15. Strand breaks in plasmid DNA following positional changes of Auger-electron-emitting radionuclides

    International Nuclear Information System (INIS)

    Adelstein, S.J.; Kassis, A.I.

    1996-01-01

    The purpose of our studies is to elucidate the kinetics of DNA strand breaks caused by low-energy Auger electron emitters in close proximity to DNA. Previously we have studied the DNA break yields in plasmids after the decay of indium-111 bound to DNA or free in solution. In this work, we compare the DNA break yields in supercoiled DNA of iodine-125 decaying close to DNA following DNA intercalation, minor-groove binding, or surface binding, and at a distance form DNA. Supercoiled DNA, stored at 4 C to accumulate radiation dose from the decay of 125 I, was then resolved by gel electrophoresis into supercoiled, nicked circular, and linear forms, representing undamaged DNA, single-strand breaks, and double-strand breaks respectively. DNA-intercalated or groove-bound 125 I is more effective than surface-bound radionuclide or 125 I free in solution. The hydroxyl radical scavenger DMSO protects against damage by 125 I free in solution but has minimal effect on damage by groove-bound 125 I. (orig.)

  16. A scanning Auger electron spectrometer for internal surface analysis of Large Electron Positron 2 superconducting radio-frequency cavities

    Science.gov (United States)

    Benvenuti, C.; Cosso, R.; Genest, J.; Hauer, M.; Lacarrère, D.; Rijllart, A.; Saban, R.

    1996-08-01

    A computer-controlled surface analysis instrument, incorporating static Auger electron spectroscopy, scanning Auger mapping, and secondary electron imaging, has been designed and built at CERN to study and characterize the inner surface of superconducting radio-frequency cavities to be installed in the Large Electron Positron collider. A detailed description of the instrument, including the analytical head, the control system, and the vacuum system is presented. Some recent results obtained from the cavities provide examples of the instrument's capabilities.

  17. Features of atomic images reconstructed from photoelectron, Auger electron, and internal detector electron holography using SPEA-MEM

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Tomohiro, E-mail: matusita@spring8.or.jp [Japan Synchrotron Radiation Research Institute, SPring-8, Sayo, Hyogo 679-5198 (Japan); Matsui, Fumihiko [Graduate School of Materials Science, Nara Institute of Science and Technology, Ikoma, Nara 630-0192 (Japan)

    2014-08-15

    Highlights: • We develop a 3D atomic image reconstruction algorithm for photoelectron, Auger electron, and internal detector holography. • We examine the shapes of the atomic images reconstructed by using a developed kernel function. • We examine refraction effect at surface, limitation effect of the hologram data, energy resolution effect, and angular resolution effect. • These discussions indicate the experimental requirements to obtain the clear 3D atomic image. - Abstract: Three-dimensional atomic images can be reconstructed from photoelectron, Auger electron, and internal detector electron holograms using a scattering pattern extraction algorithm using the maximum entropy method (SPEA-MEM) that utilizes an integral transform. An integral kernel function for the integral transform is the key to clear atomic image reconstruction. We composed the kernel function using a scattering pattern function and estimated its ability. Image distortion caused by multiple scattering was also evaluated. Four types of Auger electron wave functions were investigated, and the effect of these wave function types was estimated. In addition, we addressed refraction at the surface, the effects of data limitation, and energy and angular resolutions.

  18. Many-electron effect in the resonant Auger electron spectroscopy spectra of adsorbates

    International Nuclear Information System (INIS)

    Ohno, Masahide

    2007-01-01

    It is shown by a many-body theory that a resonantly excited core hole state in a chemisorbed molecule such as CO/Ni, CO/Pd, and CO/Pt relaxes to a fully relaxed one, i.e., the ionized core hole state of the smallest binding energy observed by photoelectron spectroscopy, before the core hole decays so that the resonant Auger electron spectroscopy (RAES) spectrum shows the normal Auger decay spectrum. It is shown by a many-body theory that the Auger peaks on the higher kinetic energy (K.E.) side in the RAES or AES spectrum, i.e., so called back-bonding peaks, are the two-hole states consisting of a valence hole and a hole in the adsorbate-substrate hybrid states below the substrate Fermi level. The latter hole is the change in the density of the hybrid states occupied by the screening electron from the core hole state to the valence-hole state. The difference between the back-bonding peak energy and the single valence-hole energy provides an important information about the change in the density of the hybrid states occupied by the screening electron from the core hole state to the valence-hole state. The difference between the RAES spectrum measured at the resonance energy and the AES spectrum measured at far above the ionization limit shows the competition between relaxation and decay of shakeup satellites such as the charge transfer (CT) shakeup. The relaxation rate of the CT shakeup state can be determined by Auger-photoelectron coincidence spectroscopy (APECS)

  19. Development of DNA-based radiopharmaceuticals carrying Auger-electron emitters for anti-gene radiotherapy

    International Nuclear Information System (INIS)

    Panyutin, I.G.; Winters, T.A.; Feinendegen, L.E.; Neumann, R.D.

    2000-01-01

    Targeting of radiation damage to specific DNA sequences is the essence of antigene radiotherapy. This technique also provides a tool to study molecular mechanisms of DNA repair on a defined, single radio damaged site. It was achieved such sequence-specific radio damage by combining the highly localized DNA damage produced by the decay of Auger-electron-emitters such as 125 I with the sequence-specific action of triplex-forming oligonucleotides (TFO). TFO complementary to polypurine-polypyrimidine regions of human genes were synthesized and labeled with 125 I-dCTP by the primer extension method. 125 I-TFO were delivered into cells with several delivery systems. In addition, human enzymes capable of supporting DNA single-strand-break repair were isolated and assessed for their role in the repair of this lesion. Also, the mutagenicity and repairability of 125 I-TFO-induced double strand breaks (DSB) were assessed by repair of plasmid possessing a site-specific DSB lesion. Using plasmids containing target polypurine-polypyrimidine tracts, it was obtained the fine structure of sequence-specific DNA breaks produced by decay of 125 I with single-nucleotide resolution. It was showed that the designed 125 I-TFO in nanomolar concentrations could bind to and introduce double-strand breaks into the target sequences in situ, i.e., within isolated nuclei and intact digitonin-permeabilized cells. It was also showed 125 I-TFO-induced DSB to be highly mutagenic lesions resulting in a mutation frequency of nearly 80%, with deletions comprising the majority of mutations. The results obtained demonstrate the ability of 125 I-TFO to target specific sequences in their natural environment - within eukaryotic nucleus. Repair of 125 I-TFO-induced DNA damage should typically result in mutagenic gene inactivation

  20. Accelerator based production of auger-electron-emitting isotopes for radionuclide therapy

    International Nuclear Information System (INIS)

    Thisgaard, H.

    2008-08-01

    In this research project the focus has been on the identification and production of new, unconventional Auger-electron-emitting isotopes for targeted radionuclide therapy of cancer. Based on 1st principles dosimetry calculations on the subcellular level, the Auger-emitter 119Sb has been identified as a potent candidate for therapy. The corresponding imaging analogue 117Sb has been shown from planar scintigraphy and single-photon emission computed tomography (SPECT) to be suitable for SPECT-based dosimetry of a future Sb-labeled radiopharmaceutical. The production method of these radioisotopes has been developed using a low-energy cyclotron via the nuclear reactions 119Sn(p,n)119Sb and 117Sn(p,n)117Sb including measurements of the excitation function for the former reaction. Moreover, a new high-yield radiochemical separation method has been developed to allow the subsequent separation of the produced 119Sb from the enriched 119Sn target material with high radionuclidic- and chemical purity. A method that also allows efficient recovery of the 119Sn for recycling. To demonstrate the ability of producing therapeutic quantities of 119Sb and other radioisotopes for therapy with a low-energy cyclotron, two new 'High Power' cyclotron targets were developed in this study. The target development was primarily based on theoretical thermal modeling calculations using finite-element-analysis software. With these targets, I have shown that it will be possible to produce several tens of GBq of therapeutics isotopes (e.g. 119Sb or 64Cu) using the PETtrace cyclotron commonly found at the larger PET-centers in the hospitals. Finally, research in a new method to measure the radiotoxicity of Auger-emitters invitro using cellular microinjection has been carried out. The purpose of this method is to be able to experimentally evaluate and compare the potency of the new and unconventional Auger-emitters (e.g. 119Sb). However, due to experimental complications, the development of this

  1. Accelerator based production of auger-electron-emitting isotopes for radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Thisgaard, H.

    2008-08-15

    In this research project the focus has been on the identification and production of new, unconventional Auger-electron-emitting isotopes for targeted radionuclide therapy of cancer. Based on 1st principles dosimetry calculations on the subcellular level, the Auger-emitter 119Sb has been identified as a potent candidate for therapy. The corresponding imaging analogue 117Sb has been shown from planar scintigraphy and single-photon emission computed tomography (SPECT) to be suitable for SPECT-based dosimetry of a future Sb-labeled radiopharmaceutical. The production method of these radioisotopes has been developed using a low-energy cyclotron via the nuclear reactions 119Sn(p,n)119Sb and 117Sn(p,n)117Sb including measurements of the excitation function for the former reaction. Moreover, a new high-yield radiochemical separation method has been developed to allow the subsequent separation of the produced 119Sb from the enriched 119Sn target material with high radionuclidic- and chemical purity. A method that also allows efficient recovery of the 119Sn for recycling. To demonstrate the ability of producing therapeutic quantities of 119Sb and other radioisotopes for therapy with a low-energy cyclotron, two new 'High Power' cyclotron targets were developed in this study. The target development was primarily based on theoretical thermal modeling calculations using finite-element-analysis software. With these targets, I have shown that it will be possible to produce several tens of GBq of therapeutics isotopes (e.g. 119Sb or 64Cu) using the PETtrace cyclotron commonly found at the larger PET-centers in the hospitals. Finally, research in a new method to measure the radiotoxicity of Auger-emitters invitro using cellular microinjection has been carried out. The purpose of this method is to be able to experimentally evaluate and compare the potency of the new and unconventional Auger-emitters (e.g. 119Sb). However, due to experimental complications, the development

  2. Auger electron spectroscopy and Rutherford backscattering studies of copper in 2024-T3 aluminum following electrochemical anodization in phosphoric acid

    Science.gov (United States)

    Solomon, J. S.

    1981-05-01

    The effects of the electrochemical anodization of dioxidized 2024-T3 aluminum on copper were characterized by Auger electron spectroscopy and Rutherford backscattering. Anodization was performed in phosphoric acid at constant potential. Data is presented which shows that constant potential anodization of 2024-T3 is more efficient than aluminum in terms of oxide growth rates for short anodization times. However the maximum anodic oxide thickness achievable on the alloy is less than the pure metal. Copper is shown to be enriched at the oxide metal interface because of its diffusion from the bulk during anodization. The presence of copper at the oxide-metal interface is shown to affect oxide morphology.

  3. L-MM Auger electron production in 0.3-1.6 MeV Kr-Kr collisions

    International Nuclear Information System (INIS)

    DeGroot, P.; Zarcone, M.J.; Kessel, Q.C.; Connecticut Univ., Storrs

    1987-01-01

    Relative total cross sections for Kr L-Auger electron emission are presented and compared with the corresponding X-ray data of Woerlee and Shanker and coworkers. These data sets all show the same incident ion energy dependence, indicating a constant fluorescence yield for the collision conditions under consideration. These data are also in agreement with a rotational coupling calculation by shanker and coworkers that was carried out within the framework of the one-electron molecular orbital model of Fano and Lichten. (orig.)

  4. Auger electron and X-ray photoelectron spectroscopic study of the biocorrosion of copper by alginic acid polysaccharide

    Science.gov (United States)

    Jolley, John G.; Geesey, Gill G.; Hankins, Michael R.; Wright, Randy B.; Wichlacz, Paul L.

    1989-08-01

    Thin films (3.4 nm) of copper on germanium substrates were exposed to 2% alginic acid polysaccharide aqueous solution. Pre- and post-exposure characterization were done by Auger electron spectroscopy and X-ray photoelectron spectroscopy. Ancillary graphite furnace atomic absorption spectroscopy was used to monitor the removal process of the copper thin film from the germanium substrate. Results indicate that some of the copper was oxidized by the alginic acid solution. Some of the copper was removed from the Cu/Ge interface and incorporated into the polymer matrix. Thus, biocorrosion of copper was exhibited by the alginic acid polysaccharide.

  5. Growth and trends in Auger-electron spectroscopy and x-ray photoelectron spectroscopy for surface analysis

    International Nuclear Information System (INIS)

    Powell, C.J.

    2003-01-01

    A perspective is given of the development and use of surface analysis, primarily by Auger-electron spectroscopy (AES) and x-ray photoelectron spectroscopy (XPS), for solving scientific and technological problems. Information is presented on growth and trends in instrumental capabilities, instrumental measurements with reduced uncertainties, knowledge of surface sensitivity, and knowledge and effects of sample morphology. Available analytical resources are described for AES, XPS, and secondary-ion mass spectrometry. Finally, the role of the American Vacuum Society in stimulating improved surface analyses is discussed

  6. Auger electron spectroscopy analysis of high metal content micro-structures grown by electron beam induced deposition

    International Nuclear Information System (INIS)

    Cicoira, F.; Hoffmann, P.; Olsson, C.O.A.; Xanthopoulos, N.; Mathieu, H.J.; Doppelt, P.

    2005-01-01

    An auger electron spectroscopy study was carried out on Rh-containing micro-structures grown by electron beam induced deposition (EBID) of the iso-structural and iso-electronic precursors [RhCl(PF 3 ) 2 ] 2 and [RhCl(CO) 2 ] 2 . A material containing between 55 and 60 at.% Rh was obtained from both precursors. The chemical composition of structures grown from the two different precursors indicates a similar decomposition mechanism. Deposits grown from [RhCl(PF 3 ) 2 ] 2 showed a chemical composition independent of electron energy and electron dose in the investigated range of conditions

  7. Molecular effects in carbon K-shell Auger-electron production by 0.6-2.0 MeV protons and extraction of an atomic cross section

    International Nuclear Information System (INIS)

    McDaniel, F.D.; Lapicki, G.

    1987-01-01

    Carbon K-shell Auger-electron production cross sections are reported for 0.6-2.0 MeV protons incident on CH 4 (methane), C 2 H 2 (acetylene), C 2 H 4 (ethylene), C 2 H 6 (ethane), n-C 4 H 10 (normal butane), i-C 4 H 10 (isobutane), C 6 H 6 (benzene), CO (carbon monoxide), and CO 2 (carbon dioxide). A constant-energy mode 45 0 parallel-plate electrostatic analyzer was used for detection of Auger electrons. The carbon KLL Auger-electron cross sections for all molecules were found to be lower than that found for CH 4 by 9-23%. All carbon KLL Auger-electron data could be brought into agreement when corrected for the chemical shift of the carbon K-shell binding energy in molecules and for intramolecular scattering. KLL Auger-electron production cross sections are compared to first Born and ECPSSR theories and show good agreement with both after the chemical shift of the carbon K-shell binding energy in molecules and the effects of intramolecular scattering are considered. (orig.)

  8. An Auger electron spectroscopy study on the anodization process of high-quality thin-film capacitors made of hafnium

    International Nuclear Information System (INIS)

    Noya, Atsushi; Sasaki, Katsutaka; Umezawa, Toshiji

    1989-01-01

    Formation process of the anodic oxide film of hafnium for use as a thin-film capacitor has been examined by the current-voltage characteristics of the anodization and the in-depth analysis of formed oxide using Auger electron spectroscopy. It is found that the oxide growth obeys three different rate laws such as the linear rate law at first and next the parabolic rate law during the constant current anodization, and then the reciprocal logarithmic rate law during the constant voltage anodization following after the constant current process. From the Auger electron spectroscopy analysis, it is found that the shape of the compositional depth profile of the grown oxide film varies associating with the rate law of oxidation obeyed. The variation of depth profile correlating with the rate law is discussed with respect to each elementary process such as the transport and/or the reaction of chemical species interpreted from the over-all behavior of anodization process. It is revealed that the stoichiometric film having an interface with sharp transition, which is favorable for obtaining excellent electrical properties of the capacitor, can be obtained under the condition that the phase-boundary reaction is the rate-determining step of the anodization. The constant voltage anodization process also satisfies such circumstances and therefore can be favorable method for preparing highquality thin-film capacitors. (author)

  9. Effective attenuation lengths for quantitative determination of surface composition by Auger-electron spectroscopy and X-ray photoelectron spectroscopy

    International Nuclear Information System (INIS)

    Jablonski, A.; Powell, C.J.

    2017-01-01

    Highlights: • Effective attenuation lengths (EALs) for determination of surface composition by XPS. • Considerable difference from EALs used for overlayer thickness measurements. • New analytical algorithms for calculating the effective attenuation length. - Abstract: The effective attenuation length (EAL) is normally used in place of the inelastic mean free path (IMFP) to account for elastic-scattering effects when describing the attenuation of Auger electrons and photoelectrons from a planar substrate by an overlayer film. An EAL for quantitative determination of surface composition by Auger-electron spectroscopy (AES) or X-ray photoelectron spectroscopy (XPS) is similarly useful to account for elastic-scattering effects on the signal intensities. We calculated these EALs for four elemental solids (Si, Cu, Ag, and Au) and for energies between 160 eV and 1.4 keV. The XPS calculations were made for two instrumental configurations while the AES calculations were made from the XPS formalism after “switching off” the XPS anisotropy. The EALs for quantitative determination of surface composition by AES and XPS were weak functions of emission angle for emission angles between 0 and 50°. The ratios of the average values of these EALs to the corresponding IMFPs could be fitted to a second-order function of the single-scattering albedo, a convenient measure of the strength of elastic-scattering effects. EALs for quantitative determination of surface composition by AES and XPS for other materials can be simply found from this relationship.

  10. High energy resolution and first time-dependent positron annihilation induced Auger electron spectroscopty

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, Jakob

    2010-04-03

    It was the aim of this thesis to improve the existing positron annihilation induced Auger spectrometer at the highly intense positron source NEPOMUC (NEutron induced POsitron source MUniCh) in several ways: Firstly, the measurement time for a single spectrum should be reduced from typically 12 h to roughly 1 h or even less. Secondly, the energy resolution, which amounted to {delta}E/E{approx}10%, should be increased by at least one order of magnitude in order to make high resolution positron annihilation induced Auger spectroscopy (PAES)-measurements of Auger transitions possible and thus deliver more information about the nature of the Auger process. In order to achieve these objectives, the PAES spectrometer was equipped with a new electron energy analyzer. For its ideal operation all other components of the Auger analysis chamber had to be adapted. Particularly the sample manipulation and the positron beam guidance had to be renewed. Simulations with SIMION {sup registered} ensured the optimal positron lens parameters. After the adjustment of the new analyzer and its components, first measurements illustrated the improved performance of the PAES setup: Firstly, the measurement time for short overview measurements was reduced from 3 h to 420 s. The measurement time for more detailed Auger spectra was shortened from 12 h to 80 min. Secondly, even with the reduced measurement time, the signal to noise ratio was also enhanced by one order of magnitude. Finally, the energy resolution was improved to {delta}E/E < 1. The exceptional surface sensitivity and elemental selectivity of PAES was demonstrated in measurements of Pd and Fe, both coated with Cu layers of varying thickness. PAES showed that with 0.96 monolayer of Cu on Fe, more than 55% of the detected Auger electrons stem from Cu. In the case of the Cu coated Pd sample 0.96 monolayer of Cu resulted in a Cu Auger fraction of more than 30% with PAES and less than 5% with electron induced Auger spectroscopy

  11. Correlation between energy deposition and molecular damage from Auger electrons: A case study of ultra-low energy (5–18 eV) electron interactions with DNA

    Energy Technology Data Exchange (ETDEWEB)

    Rezaee, Mohammad, E-mail: Mohammad.Rezaee@USherbrooke.ca; Hunting, Darel J.; Sanche, Léon [Groupe en Sciences des Radiations, Département de Médecine Nucléaire et Radiobiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4 (Canada)

    2014-07-15

    Purpose: The present study introduces a new method to establish a direct correlation between biologically related physical parameters (i.e., stopping and damaging cross sections, respectively) for an Auger-electron emitting radionuclide decaying within a target molecule (e.g., DNA), so as to evaluate the efficacy of the radionuclide at the molecular level. These parameters can be applied to the dosimetry of Auger electrons and the quantification of their biological effects, which are the main criteria to assess the therapeutic efficacy of Auger-electron emitting radionuclides. Methods: Absorbed dose and stopping cross section for the Auger electrons of 5–18 eV emitted by{sup 125}I within DNA were determined by developing a nanodosimetric model. The molecular damages induced by these Auger electrons were investigated by measuring damaging cross section, including that for the formation of DNA single- and double-strand breaks. Nanoscale films of pure plasmid DNA were prepared via the freeze-drying technique and subsequently irradiated with low-energy electrons at various fluences. The damaging cross sections were determined by employing a molecular survival model to the measured exposure–response curves for induction of DNA strand breaks. Results: For a single decay of{sup 125}I within DNA, the Auger electrons of 5–18 eV deposit the energies of 12.1 and 9.1 eV within a 4.2-nm{sup 3} volume of a hydrated or dry DNA, which results in the absorbed doses of 270 and 210 kGy, respectively. DNA bases have a major contribution to the deposited energies. Ten-electronvolt and high linear energy transfer 100-eV electrons have a similar cross section for the formation of DNA double-strand break, while 100-eV electrons are twice as efficient as 10 eV in the induction of single-strand break. Conclusions: Ultra-low-energy electrons (<18 eV) substantially contribute to the absorbed dose and to the molecular damage from Auger-electron emitting radionuclides; hence, they should

  12. Origin of Si(LMM) Auger Electron Emission from Silicon and Si-Alloys by keV Ar+ Ion Bombardment

    Science.gov (United States)

    Iwami, Motohiro; Kim, Su Chol; Kataoka, Yoshihide; Imura, Takeshi; Hiraki, Akio; Fujimoto, Fuminori

    1980-09-01

    Si(LMM) Auger electrons emitted from specimens of pure silicon and several Si-alloys (Ni-Si, Pd-Si and Cu-Si) under keV Ar+ ion bombardment, were examined. In the Auger spectra from all specimens studied there were four peaks at energies of 92, 86, 76 and 66 eV. The Auger signal intensity varied considerably with both the incident angle and the energy of the primary ion beam. It is proposed that the Auger electrons are emitted from silicon atoms (or ions) just beneath the specimen surface but free from the bulk network.

  13. Origin of Si(LMM) Auger electron emission from silicon and Si-alloys by keV Ar/sup +/ ion bombardment

    Energy Technology Data Exchange (ETDEWEB)

    Iwami, M; Kim, S; Kataoka, Y; Imura, T; Hiraki, A [Osaka Univ., Suita (Japan). Faculty of Engineering

    1980-09-01

    Si(LMM) Auger electrons emitted from specimens of pure silicon and several Si-alloys (Ni-Si, Pd-Si and Cu-Si) under keV Ar/sup +/ ion bombardment, were examined. In the Auger spectra from all specimens studied there were four peaks at energies of 92, 86, 76 and 66 eV. The Auger signal intensity varied considerably with both the incident angle and the energy of the primary ion beam. It is proposed that the Auger electrons are emitted from silicon atoms (or ions) just beneath the specimen surface but free from the bulk network.

  14. Auger electron spectroscopy for the determination of sex and age related Ca/P ratio at different bone sites

    International Nuclear Information System (INIS)

    Balatsoukas, Ioannis; Kourkoumelis, Nikolaos; Tzaphlidou, Margaret

    2010-01-01

    The Ca/P ratio of normal cortical and trabecular rat bone was measured by Auger electron spectroscopy (AES). Semiquantitative analysis was carried out using ratio techniques to draw conclusions on how age, sex and bone site affect the relative composition of calcium and phosphorus. Results show that Ca/P ratio is not sex dependent; quite the opposite, bone sites exhibit variations in elemental stoichiometry where femoral sections demonstrate higher Ca/P ratio than rear and front tibias. Age-related changes are more distinct for cortical bone in comparison with the trabecular bone. The latter's Ca/P ratio remains unaffected from all the parameters under study. This study confirms that AES is able to successfully quantify bone mineral main elements when certain critical points, related to the experimental conditions, are addressed effectively.

  15. Ion-induced Auger electron spectroscopy: a new detection method for compositional homogeneities of alloyed atoms in silicon

    Energy Technology Data Exchange (ETDEWEB)

    Hiraki, A [Osaka Univ., Japan; Imura, T; Iwami, M; Kim, S C; Ushita, K; Okamoto, H; Hamakawa, Y

    1979-09-01

    Auger spectra of Si LMM transitions induced by keV Ar/sup +/ ion bombardment of Si alloy systems have been studied. The spectra observed are composed of two well-defined peaks termed elsewhere the atomic-like and bulk-like peaks, repsectively. A clear correlation has been found between the intensity of the atomic-like peak lying at 88 eV and the content of the foreign atoms alloyed with Si. Experiments were carried out on metallic silicides, or Si alloys with Au, Cu, Pd and Ni, and covalently bonded non-metallic Si alloys of C and H. From these studies, we propose that ion-induced Auger electron spectroscopy might be a useful tool for the determination of alloyed foreign atoms as well as for the study of their compositional homogeneity in binary alloy systems of silicon.

  16. Radioactive gold nanoparticles with beta energy and auger electron cascades in nanomedicine: green nanotechnology and radiochemical approaches

    International Nuclear Information System (INIS)

    Katti, Kattesh V.

    2016-01-01

    In our continued efforts to apply Green Nanotechnology for the development of therapeutic radioactive gold nanoparticles, we have developed a new generation of 198 Au theranostic probes. Laminin receptors are overexpressed in a large number of human tumors and the high in vivo affinity of EGCG toward Laminin receptors has allowed us to develop Laminin receptor specific radioactive gold nanoparticles to achieve tumor specificity. This lecture will provide: (a) Oncological aspects of Auger electrons through nanomedicine; (b) details on the intervention of nuclear activation analysis and various radioanalytical approaches for the production of tumor specific radioactive gold-198 nanoparticles; and (c) full in vivo investigations on therapeutic properties of EGCG-198-AuNP agent in treating prostate tumors

  17. Thermal effects in equilibrium surface segregation in a copper/10-atomic-percent-aluminum alloy using Auger electron spectroscopy

    Science.gov (United States)

    Ferrante, J.

    1972-01-01

    Equilibrium surface segregation of aluminum in a copper-10-atomic-percent-aluminum single crystal alloy oriented in the /111/ direction was demonstrated by using Auger electron spectroscopy. This crystal was in the solid solution range of composition. Equilibrium surface segregation was verified by observing that the aluminum surface concentration varied reversibly with temperature in the range 550 to 850 K. These results were curve fitted to an expression for equilibrium grain boundary segregation and gave a retrieval energy of 5780 J/mole (1380 cal/mole) and a maximum frozen-in surface coverage three times the bulk layer concentration. Analyses concerning the relative merits of sputtering calibration and the effects of evaporation are also included.

  18. Auger electron spectroscopy study of initial stages of oxidation in a copper - 19.6-atomic-percent-aluminum alloy

    Science.gov (United States)

    Ferrante, J.

    1973-01-01

    Auger electron spectroscopy was used to examine the initial stages of oxidation of a polycrystalline copper - 19.6 a/o-aluminum alloy. The growth of the 55-eV aluminum oxide peak and the decay of the 59-, 62-, and 937-eV copper peaks were examined as functions of temperature, exposure, and pressure. Pressures ranged from 1x10 to the minus 7th power to 0.0005 torr of O2. Temperatures ranged from room temperature to 700 C. A completely aluminum oxide surface layer was obtained in all cases. Complete disappearance of the underlying 937-eV copper peak was obtained by heating at 700 C in O2 at 0.0005 torr for 1 hr. Temperature studies indicated that thermally activated diffusion was important to the oxidation studies. The initial stages of oxidation followed a logarithmic growth curve.

  19. Growth and structure of rapid thermal silicon oxides and nitroxides studied by spectroellipsometry and Auger electron spectroscopy

    Science.gov (United States)

    Gonon, N.; Gagnaire, A.; Barbier, D.; Glachant, A.

    1994-11-01

    Rapid thermal oxidation of Czochralski-grown silicon in either O2 or N2O atmospheres have been studied using spectroellipsometry and Auger electron spectroscopy. Multiwavelength ellipsometric data were processed in order to separately derive the thickness and refractive indexes of rapid thermal dielectrics. Results revealed a significant increase of the mean refractive index as the film thickness falls below 20 nm for both O2 or N2O oxidant species. A multilayer structure including an about 0.3-nm-thick interfacial region of either SiO(x) or nitroxide in the case of O2 and N2O growth, respectively, followed by a densified SiO2 layer, was found to accurately fit the experimental data. The interfacial region together with the densified state of SiO2 close to the interface suggest a dielectric structure in agreement with the continuous random network model proposed for classical thermal oxides. Auger electron spectroscopy analysis confirmed the presence of noncrystalline Si-Si bonds in the interfacial region, mostly in the case of thin oxides grown in O2. It was speculated that the initial fast growth regime was due to a transient oxygen supersaturation in the interfacial region. Besides, the self-limiting growth in N2O was confirmed and explained in agreement with several recently published data, by the early formation of a very thin nitride or oxynitride membrane in the highly densified oxide beneath the interface. The beneficial effect of direct nitrogen incorporation by rapid thermal oxidation in N2O instead of O2 for the electrical behavior of metal-oxide-semiconductor capacitors is likely a better SiO2/Si lattice accommodation through the reduction of stresses and Si-Si bonds in the interfacial region of the dielectric.

  20. Evaluation of new iodinated acridine derivatives for targeted radionuclide therapy of melanoma using {sup 125}I, an Auger electron emitter

    Energy Technology Data Exchange (ETDEWEB)

    Gardette, M.; Papon, J.; Bonnet, M.; Labarre, P.; Miot-Noirault, E.; Madelmont, J. C.; Chezal, J. M.; Moins, N. [UMR 990, INSERM, Universite d' Auvergne, Clermont-Ferrand (France); Desbois, N. [EA 3660, Universite de Bourgogne, Dijon (France); Wu, T. D.; Guerquin-Kern, J. L. [U 759 INSERM, Institute Curie, Orsay (France)

    2013-06-01

    The full text of the publication follows. The increasing incidence of melanoma and the lack of effective therapy on the disseminated form have led to an urgent need for new specific therapies. Several iodo-benzamides or analogs are known to possess specific affinity for melanoma tissue. New hetero-aromatic derivatives have been designed with a cytotoxic moiety and termed DNA intercalating agents. These compounds could be applied in targeted radionuclide therapy using {sup 125}I, Auger electrons emitter which gives high-energetic localized irradiation. Two iodinated acridine derivatives have been reported to present an in vivo kinetic profile conducive to application in targeted radionuclide therapy. The aim of the present study was to perform a preclinical evaluation of these compounds. The DNA intercalating property was confirmed for both compounds. After radiolabeling with {sup 125}I, the two compounds induced in vitro a significant radiotoxicity on B16F0 melanoma cells. The acridine compound, ICF01040, appeared more radio toxic than the acridone compound, ICF01035. While cellular uptake was similar for both compounds, SIMS analysis and in vitro protocol showed a stronger affinity for melanin with ICF01035, which was able to induce a predominant scavenging process in the melanosome and restrict access to the nucleus. Nevertheless, an important radiotoxicity was measured for the two compounds while the nuclear accumulation was low. Indeed, even if nuclear localization remains the main target sensitive to Auger electrons, the cell membrane remains sensitive to {sup 125}I decays. So, these compounds may induce secondary toxic effects of irradiation, such as membrane lipid damage. Conducted to current experiments are evaluate such hypothesis. Taken together, these results suggest that ICF01040 is a better candidate for application in targeted radionuclide therapy using {sup 125}I. The next step will be in vivo evaluation, where high tumoral vectorization gives

  1. Production of Mg and Al Auger electrons by noble gas ion bombardment of Mg and Al surfaces. [3 KeV, electron promotion

    Energy Technology Data Exchange (ETDEWEB)

    Ferrante, J; Pepper, S V [National Aeronautics and Space Administration, Cleveland, Ohio (USA). Lewis Research Center

    1976-08-01

    In this letter the relative production efficiency of Mg and Al Auger electrons by He, Ne, Ar, Kr and Xe ion bombardment as a function of ion energy (<=3 keV) is reported. Some comments on the interpretation of the results in terms of electron promotion are also given.

  2. The determination of carbon, nitrogen and oxygen in TiCsub(x)Nsub(y)Osub(z) with the Auger electron spectroscopy (AES)

    International Nuclear Information System (INIS)

    Schneider, H.; Nold, E.; Miller, H.T.

    1980-01-01

    The possibility of determining the carbon, nitrogen and oxygen contents in TiCsub(x)Nsub(y)Osub(z) with the Auger-electron-spectroscopy (AES) is discussed. As an example the concentration dependence over the cross section of 1 μm thick TiN-layers is presented. (orig.)

  3. Gold removal rate by ion sputtering as a function of ion-beam voltage and raster size using Auger electron spectroscopy. Final report

    International Nuclear Information System (INIS)

    Boehning, C.W.

    1983-01-01

    Gold removal rate was measured as a function of ion beam voltage and raster size using Auger electron spectroscopy (AES). Three different gold thicknesses were developed as standards. Two sputter rate calibration curves were generated by which gold sputter rate could be determined for variations in ion beam voltage or raster size

  4. Auger electron spectroscopy analysis for growth interface of cubic boron nitride single crystals synthesized under high pressure and high temperature

    Science.gov (United States)

    Lv, Meizhe; Xu, Bin; Cai, Lichao; Guo, Xiaofei; Yuan, Xingdong

    2018-05-01

    After rapid cooling, cubic boron nitride (c-BN) single crystals synthesized under high pressure and high temperature (HPHT) are wrapped in the white film powders which are defined as growth interface. In order to make clear that the transition mechanism of c-BN single crystals, the variation of B and N atomic hybrid states in the growth interface is analyzed with the help of auger electron spectroscopy in the Li-based system. It is found that the sp2 fractions of B and N atoms decreases, and their sp3 fractions increases from the outer to the inner in the growth interface. In addition, Lithium nitride (Li3N) are not found in the growth interface by X-ray diffraction (XRD) experiment. It is suggested that lithium boron nitride (Li3BN2) is produced by the reaction of hexagonal boron nitride (h-BN) and Li3N at the first step, and then B and N atoms transform from sp2 into sp3 state with the catalysis of Li3BN2 in c-BN single crystals synthesis process.

  5. The effect of 111In radionuclide distance and auger electron energy on direct induction of DNA double-strand breaks: a Monte Carlo study using Geant4 toolkit.

    Science.gov (United States)

    Piroozfar, Behnaz; Raisali, Gholamreza; Alirezapour, Behrouz; Mirzaii, Mohammad

    2018-04-01

    In this study, the effect of 111 In position and Auger electron energy on direct induction of DSBs was investigated. The Geant4-DNA simulation toolkit was applied using a simple B-DNA form extracted from PDBlib library. First, the simulation was performed for electrons with energies of 111 In and equal emission probabilities to find the most effective electron energies. Then, 111 In Auger electrons' actual spectrum was considered and their contribution in DSB induction analysed. The results showed that the most effective electron energy is 183 eV, but due to the higher emission probability of 350 eV electrons, most of the DSBs were induced by the latter electrons. Also, it was observed that most of the DSBs are induced by electrons emitted within 4 nm of the central axis of the DNA and were mainly due to breaks with <4 base pairs distance in opposing strands. Whilst, when 111 In atoms are very close to the DNA, 1.3 DSBs have been obtained per decay of 111 In atoms. The results show that the most effective Auger electrons are the 350 eV electrons from 111 In atoms with <4 nm distance from the central axis of the DNA which induce ∼1.3 DSBs per decay when bound to the DNA. This value seems reasonable when compared with the reported experimental data.

  6. Studies Of Oxidation And Thermal Reduction Of The Cu(100) Surface Using Positron Annihilation Induced Auger Electron Spectroscopy

    Science.gov (United States)

    Fazleev, N. G.; Nadesalingam, M. P.; Maddox, W.; Weiss, A. H.

    2011-06-01

    Positron annihilation induced Auger electron spectroscopy (PAES) measurements from the surface of an oxidized Cu(100) single crystal show a large increase in the intensity of the annihilation induced Cu M2,3VV Auger peak as the sample is subjected to a series of isochronal anneals in vacuum up to annealing temperature 300 °C. The PAES intensity then decreases monotonically as the annealing temperature is increased to ˜550 °C. Experimental positron annihilation probabilities with Cu 3p and O 1s core electrons are estimated from the measured intensities of the positron annihilation induced Cu M2,3VV and O KLL Auger transitions. PAES results are analyzed by performing calculations of positron surface states and annihilation probabilities of the surface-trapped positrons with relevant core electrons taking into account the charge redistribution at the surface and various surface structures associated with low and high oxygen coverages. The variations in atomic structure and chemical composition of the topmost layers of the oxidized Cu(100) surface are found to affect localization and spatial extent of the positron surface state wave function. The computed positron binding energy and annihilation characteristics reveal their sensitivity to charge transfer effects, atomic structure and chemical composition of the topmost layers of the oxidized Cu(100) surface. Theoretical positron annihilation probabilities with Cu 3p and O 1s core electrons computed for the oxidized Cu(100) surface are compared with experimental ones. The obtained results provide a demonstration of thermal reduction of the copper oxide surface after annealing at 300 °C followed by re-oxidation of the Cu(100) surface at higher annealing temperatures presumably due to diffusion of subsurface oxygen to the surface.

  7. Studies Of Oxidation And Thermal Reduction Of The Cu(100) Surface Using Positron Annihilation Induced Auger Electron Spectroscopy

    International Nuclear Information System (INIS)

    Fazleev, N. G.; Nadesalingam, M. P.; Maddox, W.; Weiss, A. H.

    2011-01-01

    Positron annihilation induced Auger electron spectroscopy (PAES) measurements from the surface of an oxidized Cu(100) single crystal show a large increase in the intensity of the annihilation induced Cu M2,3VV Auger peak as the sample is subjected to a series of isochronal anneals in vacuum up to annealing temperature 300 deg. C. The PAES intensity then decreases monotonically as the annealing temperature is increased to ∼550 deg. C. Experimental positron annihilation probabilities with Cu 3p and O 1s core electrons are estimated from the measured intensities of the positron annihilation induced Cu M 2,3 VV and O KLL Auger transitions. PAES results are analyzed by performing calculations of positron surface states and annihilation probabilities of the surface-trapped positrons with relevant core electrons taking into account the charge redistribution at the surface and various surface structures associated with low and high oxygen coverages. The variations in atomic structure and chemical composition of the topmost layers of the oxidized Cu(100) surface are found to affect localization and spatial extent of the positron surface state wave function. The computed positron binding energy and annihilation characteristics reveal their sensitivity to charge transfer effects, atomic structure and chemical composition of the topmost layers of the oxidized Cu(100) surface. Theoretical positron annihilation probabilities with Cu 3p and O 1s core electrons computed for the oxidized Cu(100) surface are compared with experimental ones. The obtained results provide a demonstration of thermal reduction of the copper oxide surface after annealing at 300 deg. C followed by re-oxidation of the Cu(100) surface at higher annealing temperatures presumably due to diffusion of subsurface oxygen to the surface.

  8. Oxygen adsorption on Cu-9 at. %Al(111) studied by low energy electron diffraction and Auger electron spectroscopy

    Science.gov (United States)

    Yoshitake, Michiko; Bera, Santanu; Yamauchi, Yasuhiro; Song, Weijie

    2003-07-01

    Cu-based alloys have been used for electric cables for long time. In the field of microelectronics, Al had been used for electrical wiring. However, it became clear that electromigration occurs in Al that causes breaking of wires in minute wirings. Due to this problem, Cu wiring is used in most advanced microprocessors. Cu metal is more corrosive than Al and Cu-based alloys with a small amount of Al is expected to solve problems both on electromigration and corrosion. The initial stage of corrosion is oxygen adsorption. We studied surface segregation of Al on Cu-9% Al(111) and oxygen adsorption on the surface with/without Al segregation in ultrahigh vacuum by low energy electron diffraction (LEED) and Auger electron spectroscopy. It was found that Al segregates on the surface to form (√3×√3)R30° structure and the structure vanishes above 595 K to give (1×1) structure while Al still segregates. The specimen was exposed to oxygen at different temperatures. The amount of oxygen uptake was not structure dependent but temperature dependent. Below 595 K, only a small amount of oxygen adsorbed. Between 595 and 870 K, oxygen adsorbed surface showed amorphous LEED pattern. The specimen was annealed at 1070 K after oxygen exposure. When the specimen was exposed oxygen below 870 K, the oxygen Auger intensity decreased significantly by annealing and the annealed surface showed (√3×√3)R30° structure at room temperature. When the specimen was exposed to oxygen at 870 K, diffused spots developed newly in LEED pattern but the pattern disappeared after 1070 K annealing while oxygen Auger intensity remained almost constant. Exposing the specimen to oxygen at 995 K resulted in clear spots in the LEED pattern, which were attributed to the (7/√3×7√3)R30° structure.

  9. DNA and chromosome breaks induced by 123I-estrogen in CHO cells

    International Nuclear Information System (INIS)

    Schwartz, J.L.

    1997-01-01

    The effects of the Auger electron-emitting isotope I-123, covalently bound to estrogen, on DNA single- and double-strand breakage and on chromosome breakage was determined in estrogen positive Chinese hamster ovary (CHO-ER) cells. Exposure to the 123 I-estrogen induced both single- and double-strand breaks with a ratio of single- to double-strand breaks of 2.2. The corresponding ratio with 60 Co gamma rays was 15.6. The dose-response was biphasic suggesting that either receptor sites are saturated at high does, or that there is a nonrandom distribution of breaks induced by the 123 I-estrogen. The 123 I-estrogen treatment induced chromosome aberrations with an efficiency of about 1 aberration for each 1,000 disintegrations per cell. This corresponds to the mean lethal dose of 123 I-estrogen for these cells suggesting that the lethal event induced by the Auger electron emitter bound to estrogen is a chromosome aberration. Most of the chromosome-type aberrations were dicentrics and rings, suggesting that 123 I-estrogen-induced chromosome breaks are rejoined. The F-ratio, the ratio of dicentrics to centric rings, was 5.8 ± 1.7, which is similar to that seen with high LET radiations. Their results suggest that I-123 bound to estrogen is an efficient clastogenic agent, that the cytotoxic damage produced by I-123 bound to estrogen is very like high LET-induced damage, and the I-123 in the estrogen-receptor-DNA complex is probably in close proximity to the sugar-phosphate backbone of the DNA

  10. Scanning Auger Electron Microscope

    Data.gov (United States)

    Federal Laboratory Consortium — A JEOL model 7830F field emission source, scanning Auger microscope.Specifications / Capabilities:Ultra-high vacuum (UHV), electron gun range from 0.1 kV to 25 kV,...

  11. Many-electron effect in the resonant L23-M23V Auger-electron spectrum of Ti metal

    International Nuclear Information System (INIS)

    Ohno, Masahide

    2006-01-01

    Above the L23 absorption edge the L 23 -M 23 V resonant Auger-electron spectroscopy (RAES) spectrum of Ti metal shows a normal L 23 -M 23 V Auger decay spectrum at a constant kinetic energy (K.E.). Here LX and MY are the atomic shells Lx and My, respectively. Apart from a weak spectral feature of the L2-M23V Auger transition appearing around the L2 edge, the RAES spectra of Ti meal show a very little difference between the L2 and L3 regions [P. Le Fevre, J. Danger, H. Magnan, D. Chandesris, J. Jupille, S. Bourgeois, M.-A. Arrio, R. Gotter, A. Verdini, A. Morgante, Phys. Rev. B69 (2004) 155421]. It is shown that the time scale of relaxation of the resonantly excited L23-hole state to the L23-electron ionized state is much shorter than that of the L23-hole decay so that the L 23 -M 23 V RAES spectrum of Ti metal resembles much the normal L 23 -M 23 V Auger decay spectrum. The relaxation of the resonantly excited L23-hole state to the fully relaxed L23-hole state before the L23-hole decays, explains the extra width which is the primary cause of the discrepancy between the experimental high resolution near edge X-ray absorption spectroscopy (XAS) spectrum of Ti metal and the one calculated by the particle-hole Green's function including the Coulomb exchange interaction between the 2p hole and the 3d electron. The time scale of relaxation of the L3V two-hole state created by the L2-L3V Coster-Kronig (CK) decay to the single L3-hole state is much shorter than that of the L3-hole decay so that the L2-L3V-L3-M23V CK preceded Auger decay spectrum resembles much the L3-M23V Auger decay one

  12. Photoelectron and Auger-electron spectra of Cl{sub 3}SiSi(CH{sub 3}){sub 3} obtained by using monochromatized synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nagaoka, Shin-ichi, E-mail: nagaoka@ehime-u.ac.jp [Department of Chemistry, Faculty of Science and Graduate School of Science and Engineering, Ehime University, Matsuyama 790-8577 (Japan); Endo, Hikaru; Nagai, Kanae [Department of Chemistry, Faculty of Science and Graduate School of Science and Engineering, Ehime University, Matsuyama 790-8577 (Japan); Takahashi, Osamu [Institute for Sustainable Sciences and Development, Hiroshima University, Higashi-Hiroshima 739-8511 (Japan); Tamenori, Yusuke [Synchrotron Radiation Research Institute/SPring-8, 1-1-1 Kouto, Sayo-cho, Sayo-gun 679-5198 (Japan); Suzuki, Isao H. [Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), 1-1 Oho, Tsukuba 305-0801 (Japan); Advanced Institute of Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba 305-8568 (Japan)

    2014-08-15

    Highlights: • Various photo- and Auger-electron spectra of Cl{sub 3}SiSi(CH{sub 3}){sub 3} vapor were measured. • The measured spectra were interpreted with the aid of some calculations. • The spectra showed profiles close to those expected from SiCl{sub 4} and Si(CH{sub 3}){sub 4}. • These results were discussed in conjunction with site-specific fragmentation. - Abstract: A variety of photoelectron and Auger-electron spectra of 1,1,1-trimethyltrichlorodisilane vapor (Cl{sub 3}SiSi(CH{sub 3}){sub 3}) were measured by using monochromatized synchrotron radiation and a hemispherical electron energy analyzer. The measured spectra were interpreted with the aid of some calculations by means of the outer valence Green's function (OVGF) method or the density-functional-theory (DFT) method. Since Cl{sub 3}SiSi(CH{sub 3}){sub 3} consists of -SiCl{sub 3} and -Si(CH{sub 3}){sub 3} moieties, the experimental core-electron binding-energies were compared with those of tetrachlorosilane and tetramethylsilane (SiCl{sub 4} and Si(CH{sub 3}){sub 4}, respectively). This comparison showed that electronic properties of Cl{sub 3}SiSi(CH{sub 3}){sub 3} hold a close correlation with those of SiCl{sub 4} and Si(CH{sub 3}){sub 4}. Si:L{sub 23}VV, Cl:L{sub 23}VV and C:KVV Auger-electron spectra of Cl{sub 3}SiSi(CH{sub 3}){sub 3} also showed profiles close to those expected from the spectra of SiCl{sub 4} and Si(CH{sub 3}){sub 4}. The results obtained here were discussed in conjunction with electronic relaxation leading to site-specific fragmentation.

  13. Interdiffusion in epitaxial, single-crystalline Au/Ag thin films studied by Auger electron spectroscopy sputter-depth profiling and positron annihilation

    International Nuclear Information System (INIS)

    Noah, Martin A.; Flötotto, David; Wang, Zumin; Reiner, Markus; Hugenschmidt, Christoph; Mittemeijer, Eric J.

    2016-01-01

    Interdiffusion in epitaxial, single-crystalline Au/Ag bilayered thin films on Si (001) substrates was investigated by Auger electron spectroscopy (AES) sputter-depth profiling and by in-situ positron annihilation Doppler broadening spectroscopy (DBS). By the combination of these techniques identification of the role of vacancy sources and sinks on interdiffusion in the Au/Ag films was possible. It was found that with precise knowledge of the concentration-dependent self-diffusion and impurity diffusion coefficients a distinction between the Darken-Manning treatment and Nernst-Planck treatment can be made, which is not possible on the basis of the determined concentration-depth profiles alone.

  14. Auger decay of 1σg and 1σu hole states of the N2 molecule. II. Young-type interference of Auger electrons and its dependence on internuclear distance

    International Nuclear Information System (INIS)

    Cherepkov, N. A.; Semenov, S. K.; Schoeffler, M. S.; Titze, J.; Petridis, N.; Jahnke, T.; Cole, K.; Schmidt, L. Ph. H.; Czasch, A.; Jagutzki, O.; Schmidt-Boecking, H.; Doerner, R.; Akoury, D.; Williams, J. B.; Landers, A. L.; Osipov, T.; Lee, S.; Prior, M. H.; Belkacem, A.; Weber, Th.

    2010-01-01

    Theoretical two-center interference patterns produced (i) by the K-shell photoionization process of the N 2 molecule and (ii) by the Auger decay process of the K-shell hole state of the N 2 molecule are compared for the case of equal photo- and Auger-electron energies of about 360 eV. The comparison shows that both the angular distribution of the photoelectrons and the angular distribution of the Auger electrons of equal energy in the molecular frame are primarily defined by the Young interference. The experimental data for the angular resolved K-shell Auger electrons as a function of the kinetic-energy release (KER) obtained earlier [Phys. Rev. A 81, 043426 (2010)] have been renormalized in order to visualize the angular variation in the regions of low Auger-electron intensities. That renormalized data are compared with the corresponding theoretical results. From the known behavior of the potential energy curves, the connection between the KER and the internuclear distance can be established. Since the Young interference pattern is sensitive to the internuclear distance in the molecule, from the measured KER dependence of the Young interference pattern one can trace the behavior of the Auger-electron angular distribution for different molecular terms as a function of internuclear distance. The results of that analysis are in a good agreement with the corresponding theoretical predictions.

  15. 111In-BnDTPA-F3: an Auger electron-emitting radiotherapeutic agent that targets nucleolin.

    Science.gov (United States)

    Cornelissen, Bart; Waller, Andrew; Target, Carol; Kersemans, Veerle; Smart, Sean; Vallis, Katherine A

    2012-02-20

    The F3 peptide (KDEPQRRSARLSAKPAPPKPEPKPKKAPAKK), a fragment of the human high mobility group protein 2, binds nucleolin. Nucleolin is expressed in the nuclei of normal cells but is also expressed on the membrane of some cancer cells. The goal was to investigate the use of 111In-labeled F3 peptide for Auger electron-targeted radiotherapy. F3 was labeled with fluorescein isothiocyanate (FITC) for confocal microscopy and conjugated to p-SCN-benzyl-diethylenetriaminepentaacetic acid (BnDTPA) for labeling with 111In to form 111In-BnDTPA-F3. MDA-MB-231-H2N (231-H2N) human breast cancer cells were exposed to 111In-BnDTPA-F3 and used in cell fractionation, γH2AX immunostaining (a marker of DNA double-strand breaks), and clonogenic assays. In vivo, biodistribution studies of 111In-BnDTPA-F3 were performed in 231-H2N xenograft-bearing mice. In tumor growth delay studies, 111In-BnDTPA-F3 (3 μg, 6 MBq/μg) was administered intravenously to 231-H2N xenograft-bearing mice once weekly for 3 weeks. Membrane-binding of FITC-F3 was observed in 231-H2N cells, and there was co-localization of FITC-F3 with nucleolin in the nuclei. After exposure of 231-H2N cells to 111In-BnDTPA-F3 for 2 h, 1.7% of 111In added to the medium was membrane-bound. Of the bound 111In, 15% was internalized, and of this, 37% was localized in the nucleus. Exposure of 231-H2N cells to 111In-BnDTPA-F3 (1 μM, 6 MBq/μg) resulted in a dose-dependent increase in γH2AX foci and in a significant reduction of clonogenic survival compared to untreated cells or cells exposed to unlabeled BnDTPA-F3 (46 ± 4.1%, 100 ± 1.8%, and 132 ± 7.7%, respectively). In vivo, tumor uptake of 111In-BnDTPA-F3 (3 μg, 6 MBq/μg) at 3-h post-injection was 1% of the injected dose per gram (%ID/g), and muscle uptake was 0.5%ID/g. In tumor growth delay studies, tumor growth rate was reduced 19-fold compared to untreated or unlabeled BnDTPA-F3-treated mice (p = 0.023). 111In-BnDTPA-F3 is internalized into 231-H2N cells and translocates

  16. Investigation of the chemistry of the dielectric/FeCoTb interface by x-ray photoelectron spectroscopy and Auger electron spectroscopy

    International Nuclear Information System (INIS)

    Stickle, W.F.; Coulman, D.

    1987-01-01

    The interfacial chemistry of magneto-optic structures of sputter deposited SiO, SiO 2 , Si 3 N 4 /FeCoTb/SiO, SiO 2 , and Si 3 N 4 was studied in detail by x-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES). XPS and AES depth profiles have revealed a substantial amount of redox chemistry at the dielectric/rare-earth transition metal interfaces. The chemical reactions occur preferentially with the terbium as revealed in the XPS portion of the study by the formation of terbium oxide and terbium silicide. In the case of Si 3 N 4 evidence of TbN/sub x/ has also been observed. ''As deposited'' and annealed samples of the magneto-optic structures are compared and contrasted. It is concluded that Si 3 N 4 is a superior dielectric for magneto-optic media

  17. Mass spectroscopy of recoiled ions, secondary ion mass spectroscopy, and Auger electron spectroscopy investigation of Y2O3-stabilized ZrO2(100) and (110)

    International Nuclear Information System (INIS)

    Herman, G.S.; Henderson, M.A.; Starkweather, K.A.; McDaniel, E.P.

    1999-01-01

    We have studied the (100) and (110) surfaces of yttria-stabilized cubic ZrO 2 using Auger electron spectroscopy, low energy electron diffraction (LEED), direct recoil spectroscopy, mass spectroscopy of recoiled ions (MSRI), and secondary ion mass spectroscopy (SIMS). The concentration of yttrium at the surface was weakly influenced by the surface structure under the experimental conditions investigated. Both MSRI and SIMS indicated a more enhanced yttrium signal than zirconium signal at the surface compared to the respective bulk concentrations. The surfaces were not very well ordered as indicated by LEED. The yttria-stabilized cubic ZrO 2 single crystal surfaces may not be a suitable model material for pure phase ZrO 2 surfaces due to significant yttria concentrations at the surface. copyright 1999 American Vacuum Society

  18. Absorbed dose evaluation of Auger electron-emitting radionuclides: impact of input decay spectra on dose point kernels and S-values.

    Science.gov (United States)

    Falzone, Nadia; Lee, Boon Q; Fernández-Varea, José M; Kartsonaki, Christiana; Stuchbery, Andrew E; Kibédi, Tibor; Vallis, Katherine A

    2017-03-21

    The aim of this study was to investigate the impact of decay data provided by the newly developed stochastic atomic relaxation model BrIccEmis on dose point kernels (DPKs - radial dose distribution around a unit point source) and S-values (absorbed dose per unit cumulated activity) of 14 Auger electron (AE) emitting radionuclides, namely 67 Ga, 80m Br, 89 Zr, 90 Nb, 99m Tc, 111 In, 117m Sn, 119 Sb, 123 I, 124 I, 125 I, 135 La, 195m Pt and 201 Tl. Radiation spectra were based on the nuclear decay data from the medical internal radiation dose (MIRD) RADTABS program and the BrIccEmis code, assuming both an isolated-atom and condensed-phase approach. DPKs were simulated with the PENELOPE Monte Carlo (MC) code using event-by-event electron and photon transport. S-values for concentric spherical cells of various sizes were derived from these DPKs using appropriate geometric reduction factors. The number of Auger and Coster-Kronig (CK) electrons and x-ray photons released per nuclear decay (yield) from MIRD-RADTABS were consistently higher than those calculated using BrIccEmis. DPKs for the electron spectra from BrIccEmis were considerably different from MIRD-RADTABS in the first few hundred nanometres from a point source where most of the Auger electrons are stopped. S-values were, however, not significantly impacted as the differences in DPKs in the sub-micrometre dimension were quickly diminished in larger dimensions. Overestimation in the total AE energy output by MIRD-RADTABS leads to higher predicted energy deposition by AE emitting radionuclides, especially in the immediate vicinity of the decaying radionuclides. This should be taken into account when MIRD-RADTABS data are used to simulate biological damage at nanoscale dimensions.

  19. WE-AB-204-12: Dosimetry at the Sub-Cellular Scale of Auger-Electron Emitter 99m-Tc in a Mouse Single Thyroid Follicle Model

    Energy Technology Data Exchange (ETDEWEB)

    Taborda, A; Benabdallah, N; Desbree, A [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-roses (France)

    2015-06-15

    Purpose: To perform a dosimetry study at the sub-cellular scale of Auger-electron emitter 99m-Tc using a mouse single thyroid cellular model to investigate the contribution of the 99m-Tc Auger-electrons to the absorbed dose and possible link to the thyroid stunning in in vivo experiments in mice, recently reported in literature. Methods: The simulation of S-values for Auger-electron emitting radionuclides was performed using both the recent MCNP6 software and the Geant4-DNA extension of the Geant4 toolkit. The dosimetric calculations were validated through comparison with results from literature, using a simple model of a single cell consisting of two concentric spheres of unit density water and for six Auger-electron emitting radionuclides. Furthermore, the S-values were calculated using a single thyroid follicle model for uniformly distributed 123-I and 125-I radionuclides and compared with published S-values. After validation, the simulation of the S-values was performed for the 99m-Tc radionuclide within the several mouse thyroid follicle cellular compartments, considering the radiative and non-radiative transitions of the 99m-Tc radiation spectrum. Results: The calculated S-values using MCNP6 are in good agreement with the results from literature, validating its use for the 99m-Tc S-values calculations. The most significant absorbed dose corresponds to the case where the radionuclide is uniformly distributed in the follicular cell’s nucleus, with a S-value of 7.8 mGy/disintegration, due mainly to the absorbed Auger-electrons. The results show that, at a sub-cellular scale, the emitted X-rays and gamma particles do not contribute significantly to the absorbed dose. Conclusion: In this work, MCNP6 was validated for dosimetric studies at the sub-cellular scale. It was shown that the contribution of the Auger-electrons to the absorbed dose is important at this scale compared to the emitted photons’ contribution and can’t be neglected. The obtained S

  20. Auger electron emitter against multiple myeloma - targeted endo-radio-therapy with 125I-labeled thymidine analogue 5-iodo-4'-thio-2'-deoxyuridine

    International Nuclear Information System (INIS)

    Morgenroth, Agnieszka; Dinger, Cornelia; Zlatopolskiy, Boris D.; Al-Momani, Ehab; Glatting, Gerhard; Mottaghy, Felix M.; Reske, Sven N.

    2011-01-01

    Introduction: Multiple myeloma (MM) is a plasma cell malignancy characterized by accumulation of malignant, terminally differentiated B cells in the bone marrow. Despite advances in therapy, MM remains an incurable disease. Novel therapeutic approaches are, therefore, urgently needed. Auger electron-emitting radiopharmaceuticals are attractive for targeted nano-irradiation therapy, given that DNA of malignant cells is selectively addressed. Here we evaluated the antimyeloma potential of the Auger electron-emitting thymidine analogue 125 I-labeled 5-iodo-4'-thio-2'-deoxyuridine ([ 125 I]ITdU). Methods: Cellular uptake and DNA incorporation of [ 125 I]ITdU were determined in fluorodeoxyuridine-pretreated KMS12BM, U266, dexamethasone-sensitive MM1.S and -resistant MM1.R cell lines. The effect of stimulation with interleukin 6 (IL6) or insulin-like growth factor 1 (IGF1) on the intracellular incorporation of [ 125 I]ITdU was investigated in cytokine-sensitive MM1.S and MM1.R cell lines. Apoptotic cells were identified using Annexin V. Cleavage of caspase 3 and PARP was visualized by Western blot. DNA fragmentation was investigated using laddering assay. Therapeutic efficiency of [ 125 I]ITdU was proven by clonogenic assay. Results: [ 125 I]ITdU was shown to be efficiently incorporated into DNA of malignant cells, providing a promising mechanism for delivering highly toxic Auger radiation emitters into tumor DNA. [ 125 I]ITdU had a potent antimyeloma effect in cell lines representing distinct disease stages and, importantly, in cell lines sensitive or resistant to the conventional therapeutic agent, but was not toxic for normal plasma and bone marrow stromal cells. Furthermore, [ 125 I]ITdU abrogated the protective actions of IL6 and IGF1 on MM cells. [ 125 I]ITdU induced massive damage in the DNA of malignant plasma cells, which resulted in efficient inhibition of clonogenic growth. Conclusion: These studies may provide a novel treatment strategy for overcoming

  1. Magnetooptic effects and Auger electron spectroscopy of two-layer NiFe-Dy and Fe-Dy films with nonuniform layers

    International Nuclear Information System (INIS)

    Ehdel'man, I.S.; Markov, V.V.; Khudyakov, A.E.; Ivantsov, R.D.; Bondarenko, G.V.; Ovchinnikov, S.G.; Kesler, V.G.; Parshin, A.S.; Ronzhin, I.P.

    2001-01-01

    Magneto-optical effects (magnetic circular dichroism and meridional Kerr effect) and element distribution with layer thickness in two-layer NiFe-Dy and Fe-Dy films, prepared by thermal sputtering of component in ultrahigh vacuum, are investigated. It is shown, that Dy in a two-layer film in the temperature range of 80-300 K makes constant contributions to both effects investigated which are approximately equal to the values of the effects observed in an isolated Dy film only at temperatures below the temperature T c of Dy transition into a ferromagnetic state (T c ∼ 100 K for the films under study). This behaviour of magneto-optical effects is assumed to be due to the influence of a NiFe layer spin system on magnetic state of a Dy layer, this influence is enhanced by the deep penetration of Ni and Fe ions into Dy layer as it follows from the data obtained using Auger electron spectroscopy [ru

  2. Complementary Characterization of Cu(In,Ga)Se₂ Thin-Film Photovoltaic Cells Using Secondary Ion Mass Spectrometry, Auger Electron Spectroscopy, and Atom Probe Tomography.

    Science.gov (United States)

    Jang, Yun Jung; Lee, Jihye; Jeong, Jeung-Hyun; Lee, Kang-Bong; Kim, Donghwan; Lee, Yeonhee

    2018-05-01

    To enhance the conversion performance of solar cells, a quantitative and depth-resolved elemental analysis of photovoltaic thin films is required. In this study, we determined the average concentration of the major elements (Cu, In, Ga, and Se) in fabricated Cu(In,Ga)Se2 (CIGS) thin films, using inductively coupled plasma atomic emission spectroscopy, X-ray fluorescence, and wavelengthdispersive electron probe microanalysis. Depth profiling results for CIGS thin films with different cell efficiencies were obtained using secondary ion mass spectrometry and Auger electron spectroscopy to compare the atomic concentrations. Atom probe tomography, a characterization technique with sub-nanometer resolution, was used to obtain three-dimensional elemental mapping and the compositional distribution at the grain boundaries (GBs). GBs are identified by Na increment accompanied by Cu depletion and In enrichment. Segregation of Na atoms along the GB had a beneficial effect on cell performance. Comparative analyses of different CIGS absorber layers using various analytical techniques provide us with understanding of the compositional distributions and structures of high efficiency CIGS thin films in solar cells.

  3. Many-electron effect in the Si K-LL resonant Auger-electron spectroscopy spectra of the Si delta layer in GaAs

    International Nuclear Information System (INIS)

    Ohno, Masahide

    2006-01-01

    The Si K-LL resonant Auger-electron spectroscopy (RAES) spectra of silicon delta dopped layers in GaAs with very thin capping layers show both normal Auger decay and resonant Auger decay, when the core-level electron is excited to the conduction band. The resonant Auger peak kinetic energy (KE) shows no dispersion with photon energy, except when excited by the highest energy photons [M.D. Jackson, J.M.C. Thornton, D. Lewis, A. Robinson, M. Fahy, A. Aviary, P. Weightman, Phys. Rev. B71 (2005) 075313]. The RAES spectra are analyzed using a many-body theory. The presence of resonant Auger decay and no dispersion of resonant Auger peak KE with photon energy is explained in terms of the relaxation of a metastable excited core-hole state to a stable one on the time scale of core-hole decay. The excited electron in the conduction band either delocalizes rapidly leaving the ionized Si to decay by a normal Auger decay or drops to a state localized in the Si delta layer before the core-hole decays so that the RAES spectrum has both normal Auger decay and resonant Auger decay. As a result of the relaxation, the resonant Auger peak KE does not show any dispersion with photon energy. The variations with photon energy of the normal or resonant Auger peak intensity, KE, and width are explained in a consistent manner by a many-body theory

  4. Composition profiles of several contaminated and cleaned surfaces of gold thick films on copper plates by Auger electron and secondary ion mass spectroscopies

    International Nuclear Information System (INIS)

    Komiya, S.; Mizuno, M.; Narusawa, T.; Maeda, H.; Yoshikawa, M.

    1974-01-01

    Preparation and evaluation of a clean Au film are investigated. Development of a preparation method for obtaining clean surface on a copper shell in the JFT-2a (DIVA) TOKAMAK toroidal vacuum chamber is the aim of the present work. Au films prepared by ion plating and vacuum evaporation have been analysed by a cylindrical mirror Auger electron analyser in combination with a quadrupole mass spectrometer during 2 keV Xe ion bombardment from a sputter ion gun over the whole range of thickness of several microns. Contaminants are found to segregate on the top surface and at the interface. To expose a clean Au surface by the ion bombardment, surface layers within 1000 A had to be removed from the surfaces contaminated by touching with either a naked hand or a nylon glove or covered by a small amount of Ti. Mutual diffusions across the interfaces are also analyzed as a function of the substrate temperature. A Nb sandwich layer inhibites effectively the mutual diffusion. (auth.)

  5. X-ray photoelectron and Auger electron spectroscopic study of the adsorption of molecular iodine on uranium metal and uranium dioxide

    International Nuclear Information System (INIS)

    Dillard, J.G.; Moers, H.; Klewe-Nebenius, H.; Kirch, G.; Pfennig, G.; Ache, H.J.

    1984-01-01

    The adsorption of molecular iodine on uranium metal and on uranium dioxide has been investigated at 25 0 C. Clean surfaces were prepared in an ultrahigh vacuum apparatus and were characterized by X-ray photoelectron (XPS) and X-ray and electron-induced Auger electron spectroscopies (AES). Adsorption of I 2 was studied for exposures up to 100 langmuirs (1 langmuir = 10 -6 torr s) on uranium metal and to 75 langmuirs on uranium dioxide. Above about 2-langmuir I 2 exposure on uranium, spectroscopic evidence is obtained to indicate the beginning of UI 3 formation. Saturation coverage for I 2 adsorption on uranium dioxide occurs at approximately 10-15 langmuirs. Analysis of the XPS and AES results as well as studies of spectra as a function of temperature lead to the conclusions that a dissociative chemisorption/reaction process occurs on uranium metal while nondissociative adsorption occurs on uranium dioxide. Variations in the iodine Auger kinetic energy and in the Auger parameter are interpreted in light of extra-atomic relaxation processes. 42 references, 10 figures, 1 table

  6. X-ray photoelectron spectroscopy and Auger electron spectroscopy studies on the passivation behavior of plasma-nitrided low alloy steel in nitric acid

    Energy Technology Data Exchange (ETDEWEB)

    Chyou, S.D.; Shih, H.C. (Dept. of Materials Science and Engineering, National Tsing Hua Univ., Hsinchu (Taiwan))

    1991-12-14

    Nitrided SAE 4140 steel has been passivated by concentrated nitric acid. The resulting film was characterized using a combination of surface-analytical techniques, such as X-ray photoelectron spectroscopy (XPS) to evaluate the chemical composition of the passive film. Auger electron spectroscopy (AES) combined with ion etching was used to determine the composition depth profiles of nitrided surface. It was found that preferential dissolution of iron leads to enhanced nitrogen and chromium concentrations within the oxynitrided layer. A dense protective oxynitrided layer was found to be formed on the nitrided surface when the concentration of nitric acid was as high as 8 M. The results of X-ray diffraction, XPS and AES analyses conclude that the protective nitride layer is composed of (Fe,Cr){sub 4}N, (Fe,Cr){sub 2-3}N and CrN in the inner layer, Fe{sub 2}O{sub 3}, Cr{sub 2}O{sub 3} and remnant nitrides in the middle layer and nitrides accompanying Cr(OH){sub 3}.H{sub 2}O and {gamma}'-FeOOH in the outermost layer. (orig.).

  7. Determination of the thickness distribution of a graphene layer grown on a 2″ SiC wafer by means of Auger electron spectroscopy depth profiling

    International Nuclear Information System (INIS)

    Kotis, L.; Gurban, S.; Pecz, B.; Menyhard, M.; Yakimova, R.

    2014-01-01

    Highlights: • The thickness of graphene grown on SiC was determined by AES depth profiling. • The AES depth profiling verified the presence of buffer layer on SiC. • The presence of unsaturated Si bonds in the buffer layer has been shown. • Using multipoint analysis thickness distribution of the graphene on the wafer was determined. - Abstract: Auger electron spectroscopy (AES) depth profiling was applied for determination of the thickness of a macroscopic size graphene sheet grown on 2 in. 6H-SiC (0 0 0 1) by sublimation epitaxy. The measured depth profile deviated from the expected exponential form showing the presence of an additional, buffer layer. The measured depth profile was compared to the simulated one which allowed the derivation of the thicknesses of the graphene and buffer layers and the Si concentration of buffer layer. It has been shown that the graphene-like buffer layer contains about 30% unsaturated Si. The depth profiling was carried out in several points (diameter 50 μm), which permitted the constructing of a thickness distribution characterizing the uniformity of the graphene sheet

  8. Effect of heating on the behaviors of hydrogen in C-TiC films with auger electron spectroscopy and secondary ion mass spectroscopy analyses

    International Nuclear Information System (INIS)

    Zou, Y.; Wang, L.W.; Huang, N.K.

    2007-01-01

    C-TiC films with a content of 75% TiC were prepared with magnetron sputtering deposition followed by Ar + ion bombardment. Effect of heating on the behaviors of hydrogen in C-TiC films before and after heating was studied with Auger Electron Spectroscopy and Secondary Ion Mass Spectroscopy (SIMS) analyses. SIMS depth profiles of hydrogen after H + ion implantation and thermal treatment show different hydrogen concentrations in C-TiC coatings and stainless steel. SIMS measurements show the existence of TiH, TiH 2 , CH 3 , CH 4 , C 2 H 2 bonds in the films after H + ion irradiation and the changes in the Ti LMM, Ti LMV and C KLL Auger line shape reveal that they have a good hydrogen retention ability after heating up to the temperature 393 K. All the results show that C-TiC coatings can be used as a hydrogen retainer or hydrogen permeable barrier on stainless steel to protect it from hydrogen brittleness

  9. Influence of the "surface effect" on the segregation parameters of S in Fe(100): A multi-scale modelling and Auger Electron Spectroscopy study

    Science.gov (United States)

    Barnard, P. E.; Terblans, J. J.; Swart, H. C.

    2015-12-01

    The article takes a new look at the process of atomic segregation by considering the influence of surface relaxation on the segregation parameters; the activation energy (Q), segregation energy (ΔG), interaction parameter (Ω) and the pre-exponential factor (D0). Computational modelling, namely Density Functional Theory (DFT) and the Modified Darken Model (MDM) in conjunction with Auger Electron Spectroscopy (AES) was utilized to study the variation of the segregation parameters for S in the surface region of Fe(100). Results indicate a variation in each of the segregation parameters as a function of the atomic layer under consideration. Values of the segregation parameters varied more dramatically as the surface layer is approached, with atomic layer 2 having the largest deviations in comparison to the bulk values. This atomic layer had the highest Q value and formed the rate limiting step for the segregation of S towards the Fe(100) surface. It was found that the segregation process is influenced by two sets of segregation parameters, those of the surface region formed by atomic layer 2, and those in the bulk material. This article is the first to conduct a full scale investigation on the influence of surface relaxation on segregation and labelled it the "surface effect".

  10. Surface-site-selective study of valence electronic states of a clean Si(111)-7x7 surface using Si L23VV Auger electron and Si 2p photoelectron coincidence measurements

    International Nuclear Information System (INIS)

    Kakiuchi, Takuhiro; Tahara, Masashi; Nagaoka, Shin-ichi; Hashimoto, Shogo; Fujita, Narihiko; Tanaka, Masatoshi; Mase, Kazuhiko

    2011-01-01

    Valence electronic states of a clean Si(111)-7x7 surface are investigated in a surface-site-selective way using high-resolution coincidence measurements of Si pVV Auger electrons and Si 2p photoelectrons. The Si L 23 VV Auger electron spectra measured in coincidence with energy-selected Si 2p photoelectrons show that the valence band at the highest density of states in the vicinity of the rest atoms is shifted by ∼0.95 eV toward the Fermi level (E F ) relative to that in the vicinity of the pedestal atoms (atoms directly bonded to the adatoms). The valence-band maximum in the vicinity of the rest atoms, on the other hand, is shown to be shifted by ∼0.53 eV toward E F relative to that in the vicinity of the pedestal atoms. The Si 2p photoelectron spectra of Si(111)-7x7 measured in coincidence with energy-selected Si L 23 VV Auger electrons identify the topmost surface components, and suggest that the dimers and the rest atoms are negatively charged while the pedestal atoms are positively charged. Furthermore, the Si 2p-Si L 23 VV photoelectron Auger coincidence spectroscopy directly verifies that the adatom Si 2p component (usually denoted by C 3 ) is correlated with the surface state just below E F (usually denoted by S 1 ), as has been observed in previous angle-resolved photoelectron spectroscopy studies.

  11. Effect of relaxation and decay of a charge transfer shakeup satellite on Auger-electron spectroscopy spectra and Auger-photoelectron coincidence spectroscopy spectra of adsorbates

    International Nuclear Information System (INIS)

    Ohno, Masahide

    2008-01-01

    An electron excited to an unoccupied part of adsorbate-substrate hybrid states in a chemisorbed molecule by a resonant core electron excitation or charge transfer (CT) shakeup may delocalize on time scale of core-hole decay so that the excited core-hole state relaxes partly or completely to a fully relaxed one. The Auger decay of the fully relaxed core-hole state via the relaxation of the excited one introduces an additional feature in the resonant Auger-electron spectroscopy (RAES) spectrum and the AES spectrum. However, the additional feature in the RAES spectrum is a normal AES spectrum by decay of the fully relaxed core-hole state, whereas the one in the AES spectrum is the AES spectrum by decay of the fully relaxed core-hole state broadened by the photoelectron spectroscopy (PES) CT shakeup satellite weighted by the branching ratio of the relaxation width. The discrepancies between the AES spectrum measured at high above the ionization threshold and the additional feature in the RAES spectrum consist of the symmetric-like part by the decay of the fully relaxed core-hole state via the relaxation of the CT shakeup state and the asymmetric part by the direct decay of the shakeup states. The asymmetric part increases with a decrease in the hybridization strength. This explains the variation with the hybridization strength in the discrepancies between the RAES spectra and the AES spectra of chemisorbed molecules such as CO/Ni, CO/Cu and CO/Ag. A comparison of the singles PES spectrum with the one measured in coincidence with the AES main line of a selected kinetic energy (KE) provides the delocalization rate of the excited electron in the CT shakeup state as a function of photoelectron KE. The coincidence measurement to obtain the partial singles PES spectrum is discussed

  12. Many-body effect in the resonant Ti L23-M23V Auger-electron spectroscopy spectra and Auger-photoelectron coincidence spectroscopy spectra of Ti oxides

    International Nuclear Information System (INIS)

    Ohno, Masahide

    2007-01-01

    Recently Danger et al. [J. Danger, H. Magnan, D. Chandesris, P. Le Fevre, S. Bourgeois, J. Jupille, A. Verdini, R. Gotter, A. Morgante, Phys. Rev. B 64 (2001) 045110] and Le Fevre et al. [P. Le Fevre, J. Danger, H. Magnan, D. Chandesris, J. Jupille, S. Bourgeois, M.-A. Arrio, R. Gotter, A. Verdini, A. Morgante, Phys. Rev. B 69 (2004) 155421] showed the absence of resonant Raman scattering feature in the Ti L 23 -M 23 V resonant Auger-electron spectroscopy (RAES) spectra of Ti oxides measured across the Ti 2p edges. They attributed the absence to the covalent character of the Ti-O bond which allows an effective delocalization of 3d electrons. It is shown by a many-body theory that when the time scale of relaxation of the resonantly excited core-hole state to the fully relaxed core-hole state is much shorter than that of core-hole decay, any sizeable Raman scattering is absent in the RAES spectra measured across the Ti 2p edges. The relaxation width depends on the hybridization strength and the charge transfer (CT) energy between the two states. The L 2 -L 3 V Coster-Kronig (CK) decay widths of TiO 2 and TiO 2-x are determined from the L 23 -M 23 V Auger-photoelectron coincidence spectroscopy (APECS) spectra reported in the aforementioned papers. They are about 0.18 and 0.35 eV, respectively. The CK-decay width in the reduced Ti oxide increases compared to that of TiO 2 in rutile because of filling of the 3d states just below the Fermi level in the former

  13. The participant Coster-Kronig preceded Auger transition in the resonant L2,3-M2,3V Auger electron spectrum of Ti metal

    International Nuclear Information System (INIS)

    Ohno, Masahide

    2008-01-01

    The L 2,3 -M 2,3 V resonant Auger electron spectroscopy (RAES) spectrum of Ti metal measured by Le Fevre et al. [P. Le Fevre, J. Danger, H. Magnan, D. Chandesris, J. Jupille, S. Bourgeois, M.-A. Arrio, R. Gotter, A. Verdini, A. Morgante, Phys. Rev. B69 (2004) 155421] is analyzed in the light of relaxation and decay of the resonantly excited L 2,3 -hole states. The relaxation time of the resonantly excited L 2,3 -hole state to the fully relaxed (screened) one is much shorter than the L 2,3 -hole Auger decay time, whereas the participant Coster-Kronig (CK) decay time of the resonantly excited L 2 -hole state to the fully relaxed L 3 -hole state at the L 2 resonance is as short as the relaxation time of the resonantly excited L 2 -hole state to the fully relaxed one. The excited electron is predominantly either rapidly decoupled from the L 2,3 -hole decay or annihilated by the participant CK decay. Thus, near the L 2,3 edges the L 2,3 -M 2,3 V RAES spectral peak appears at constant kinetic energy. The L 2,3 -M 2,3 V RAES spectrum shows a normal L 2,3 -M 2,3 V Auger decay profile not modulated by the density of empty d states probed by the resonant excitation. Not only the relaxation time but also the participant CK decay time depends on photon energy because they depend on the density of empty d states probed by the resonant excitation. As a result, the L 2,3 X-ray absorption spectroscopy spectral line broadening depends on photon energy

  14. The calibration of spectrometers for Auger electron and X-ray photoelectron spectrometers part I - an absolute traceable energy calibration for electron spectrometers

    International Nuclear Information System (INIS)

    Smith, G.C.; Seah, M.P.; Anthony, M.T.

    1991-01-01

    Experiments have been made to provide calibrated kinetic energy values for AES peaks in order to calibrate Auger electron spectrometers of various resolving powers. The kinetic energies are measured using a VG Scientific ESCALAB 2 which has power supplies appropriate for AES measurements in both the constant ΔE and constant ΔE/E modes. The absolute calibration of the energy scale is obtained by the development of a new measurement chain which, in turn, is calibrated in terms of the post-1990 representation of electron volts using XPS peaks with a traceable kinetic energy accuracy of 0.02 eV. The effects of instrumental and operating parameters, including the spectrometer dispersion and stray magnetic fields, are all assessed and contribute errors for three peaks not exceeding 0.06 eV and for two peaks not exceeding 0.03 eV. Calibrated positions in the direct spectrum are given for the Cu M 2,3 VV, Au N 6,7 VV, Ag M 4 NN, Cu L 3 VV and Au M 5 N 6,7 N 6,7 transitions at 0.2 eV resolution, referred to both the Standard Vacuum Level and the Fermi level. For the derivative spectrum the positions of the negative excursions are derived numerically by computer from this data and are established with the same accuracy. Data are tabulated for the above peaks in both the direct and differentiated modes for the popular resolutions of 0.15%, 0.3% and 0.6% produced by Gaussian broadening of the high resolution spectra. Differentiations are effected by both sinusoidal modulation and Savitzky-Golay functions of 2 eV and 5 eV peak-to-peak

  15. Radiation-induced biologic bystander effect elicited in vitro by targeted radiopharmaceuticals labeled with alpha-, beta-, and auger electron-emitting radionuclides.

    Science.gov (United States)

    Boyd, Marie; Ross, Susan C; Dorrens, Jennifer; Fullerton, Natasha E; Tan, Ker Wei; Zalutsky, Michael R; Mairs, Robert J

    2006-06-01

    Recent studies have shown that indirect effects of ionizing radiation may contribute significantly to the effectiveness of radiotherapy by sterilizing malignant cells that are not directly hit by the radiation. However, there have been few investigations of the importance of indirect effects in targeted radionuclide treatment. Our purpose was to compare the induction of bystander effects by external beam gamma-radiation with those resultant from exposure to 3 radiohaloanalogs of metaiodobenzylguanidine (MIBG): (131)I-MIBG (low-linear-energy-transfer [LET] beta-emitter), (123)I-MIBG (potentially high-LET Auger electron emitter), and meta-(211)At-astatobenzylguanidine ((211)At-MABG) (high-LET alpha-emitter). Two human tumor cell lines-UVW (glioma) and EJ138 (transitional cell carcinoma of bladder)-were transfected with the noradrenaline transporter (NAT) gene to enable active uptake of MIBG. Medium from cells that accumulated the radiopharmaceuticals or were treated with external beam radiation was transferred to cells that had not been exposed to radioactivity, and clonogenic survival was determined in donor and recipient cultures. Over the dose range 0-9 Gy of external beam radiation of donor cells, 2 Gy caused 30%-40% clonogenic cell kill in recipient cultures. This potency was maintained but not increased by higher dosage. In contrast, no corresponding saturation of bystander cell kill was observed after treatment with a range of activity concentrations of (131)I-MIBG, which resulted in up to 97% death of donor cells. Cellular uptake of (123)I-MIBG and (211)At-MABG induced increasing recipient cell kill up to levels that resulted in direct kill of 35%-70% of clonogens. Thereafter, the administration of higher activity concentrations of these high-LET emitters was inversely related to the kill of recipient cells. Over the range of activity concentrations examined, neither direct nor indirect kill was observed in cultures of cells not expressing the NAT and, thus

  16. Surface-site-selective study of valence electronic structures of clean Si(100)-2x1 using Si-L23VV Auger electron-Si-2p photoelectron coincidence spectroscopy

    International Nuclear Information System (INIS)

    Kakiuchi, Takuhiro; Nagaoka, Shinichi; Hashimoto, Shogo; Fujita, Narihiko; Tanaka, Masatoshi; Mase, Kazuhiko

    2010-01-01

    Valence electronic structures of a clean Si(100)-2x1 surface are investigated in a surface-site-selective way using Si-L 23 VV Auger electron-Si-2p photoelectron coincidence spectroscopy. The Si-L 23 VV Auger electron spectra measured in coincidence with Si-2p photoelectrons emitted from the Si up-atoms or Si 2nd-layer of Si(100)-2x1 suggest that the position where the highest density of valence electronic states located in the vicinity of the Si up-atoms is shifted by 0.8 eV towards lower binding energy relative to that in the vicinity of the Si 2nd-layer. Furthermore, the valence band maximum in the vicinity of the Si up-atoms is indicated to be shifted by 0.1 eV towards lower binding energy relative to that in the vicinity of the Si 2nd-layer. These results are direct evidence of the transfer of negative charge from the Si 2nd-layer to the Si up-atoms. (author)

  17. ¹¹¹In-Bn-DTPA-nimotuzumab with/without modification with nuclear translocation sequence (NLS) peptides: an Auger electron-emitting radioimmunotherapeutic agent for EGFR-positive and trastuzumab (Herceptin)-resistant breast cancer.

    Science.gov (United States)

    Fasih, Aisha; Fonge, Humphrey; Cai, Zhongli; Leyton, Jeffrey V; Tikhomirov, Ilia; Done, Susan J; Reilly, Raymond M

    2012-08-01

    Increased expression of epidermal growth factor receptors (EGFR) in breast cancer (BC) is often associated with trastuzumab (Herceptin)-resistant forms of the disease and represents an attractive target for novel therapies. Nimotuzumab is a humanized IgG(1) monoclonal antibody that is in clinical trials for treatment of EGFR-overexpressing malignancies. We show here that nimotuzumab derivatized with benzylisothiocyanate diethylenetriaminepentaacetic acid for labelling with the subcellular range Auger electron-emitter, (111)In and modified with nuclear translocation sequence (NLS) peptides ((111)In-NLS-Bn-DTPA-nimotuzumab) was bound, internalized and transported to the nucleus of EGFR-positive BC cells. Emission of Auger electrons in close proximity to the nucleus caused multiple DNA double-strand breaks which diminished the clonogenic survival (CS) of MDA-MB-468 cells that have high EGFR density (2.4 × 10(6) receptors/cell) to less than 3 %. (111)In-Bn-DTPA-nimotuzumab without NLS peptide modification was sevenfold less effective for killing MDA-MB-468 cells. (111)In-Bn-DTPA-nimotuzumab with/without NLS peptide modification were equivalently cytotoxic to MDA-MB-231 and TrR1 BC cells that have moderate EGFR density (5.4 × 10(5) or 4.2 × 10(5) receptors/cell, respectively) reducing their CS by twofold. MDA-MB-231 cells have intrinsic trastuzumab resistance due to low HER2 density, whereas TrR1 cells have acquired resistance despite HER2 overexpression. Biodistribution and microSPECT/CT imaging revealed that (111)In-NLS-Bn-DTPA-nimotuzumab exhibited more rapid elimination from the blood and lower tumour uptake than (111)In-Bn-DTPA-nimotuzumab. Tumour uptake of the radioimmunoconjugates in mice with MDA-MB-468 xenografts was high (8-16 % injected dose/g) and was blocked by administration of an excess of unlabelled nimotuzumab, demonstrating EGFR specificity. We conclude that (111)In-Bn-DTPA-nimotuzumab with/without NLS peptide modification are promising Auger

  18. Utility of γH2AX as a molecular marker of DNA double-strand breaks in nuclear medicine: applications to radionuclide therapy employing auger electron-emitting isotopes.

    Science.gov (United States)

    Mah, Li-Jeen; Orlowski, Christian; Ververis, Katherine; El-Osta, Assam; Karagiannis, Tom C

    2011-01-01

    There is an intense interest in the development of radiopharmaceuticals for cancer therapy. In particular, radiopharmaceuticals which involve targeting radionuclides specifically to cancer cells with the use of monoclonal antibodies (radioimmunotherapy) or peptides (targeted radiotherapy) are being widely investigated. For example, the ultra-short range Auger electron-emitting isotopes, which are discussed in this review, are being considered in the context of DNAtargeted radiotherapy. The efficient quantitative evaluation of the levels of damage caused by such potential radiopharmaceuticals is required for assessment of therapeutic efficacy and determination of relevant doses for successful treatment. The DNA double-strand break surrogate marker, γH2AX, has emerged as a useful biomonitor of damage and thus effectiveness of treatment, offering a highly specific and sensitive means of assessment. This review will cover the potential applications of γH2AX in nuclear medicine, in particular radionuclide therapy.

  19. Temperature-dependent surface structure, composition, and electronic properties of the clean SrTiO3(111) crystal face: Low-energy-electron diffraction, Auger-electron spectroscopy, electron energy loss, and ultraviolet-photoelectron spectroscopy studies

    International Nuclear Information System (INIS)

    Lo, W.J.; Somorjai, G.A.

    1978-01-01

    Low-energy-electron diffraction, Auger-electron spectroscopy, electron-energy-loss, and ultraviolet-photoelectron spectroscopies were used to study the structure, composition, and electron energy distribution of a clean single-crystal (111) face of strontium titanate (perovskite). The dependence of the surface chemical composition on the temperature has been observed along with corresponding changes in the surface electronic properties. High-temperature Ar-ion bombardment causes an irreversible change in the surface structure, stoichiometry, and electron energy distribution. In contrast to the TiO 2 surface, there are always significant concentrations of Ti 3+ in an annealed ordered SrTiO 3 (111) surface. This stable active Ti 3+ monolayer on top of a substrate with large surface dipole potential makes SrTiO 3 superior to TiO 2 when used as a photoanode in the photoelectrochemical cell

  20. Auger electron-emitting "1"1"1In-DTPA-NLS-CSL360 radioimmunoconjugates are cytotoxic to human acute myeloid leukemia (AML) cells displaying the CD123"+/CD131"− phenotype of leukemia stem cells

    International Nuclear Information System (INIS)

    Gao, Catherine; Leyton, Jeffrey V.; Schimmer, Aaron D.; Minden, Mark; Reilly, Raymond M.

    2016-01-01

    Chimeric IgG_1 monoclonal antibody CSL360 recognizes the CD123"+/CD131"− phenotype expressed by leukemic stem cells (LSC). Auger electron-emitting "1"1"1In-DTPA-NLS-CSL360 radioimmunoconjugates incorporating nuclear translocation sequence (NLS) peptides bound specifically to Raji cells transfected with CD123 and exhibited a K_D of 11 nmols/L in a competition receptor-binding assay using CD123-transfected CHO cells. "1"1"1In-DTPA-NLS-CSL360 was bound, internalized and transported to the nucleus of human AML-5 myeloid leukemia cells. The clonogenic survival of AML-5 cells was reduced by "1"1"1In-DTPA-NLS-CSL360 up to 3.7-fold. Isotype control "1"1"1In-DTPA-chIgG_1 was 2-fold less cytotoxic, and unlabeled CSL360, DTPA-NLS-CSL360 or free "1"1"1In acetate did not decrease cell survival. These results are promising for further evaluation of "1"1"1In-DTPA-NLS-CSL360 for Auger electron radioimmunotherapy of AML targeting the critical LSC subpopulation. - Highlights: • "1"1"1In-DTPA-NLS-CSL360 the CD123"+/CD131"− phenotype of leukemic stem cells (LSC). • "1"1"1In-DTPA-NLS-CSL360 was bound, internalized and imported into the nucleus of AML-5 leukemia cells. • "1"1"1In-DTPA-NLS-CSL360 reduced the clonogenic survival of AML-5 leukemia cells by 4-fold.

  1. Auger electron emitter against multiple myeloma - targeted endo-radio-therapy with {sup 125}I-labeled thymidine analogue 5-iodo-4'-thio-2'-deoxyuridine

    Energy Technology Data Exchange (ETDEWEB)

    Morgenroth, Agnieszka, E-mail: amorgenroth@ukaachen.de [Nuclear Medicine Clinic, University Ulm, Albert-Einstein-Allee 23, D-89081 Ulm (Germany); Nuclear Medicine Clinic, University Aachen, RWTH, Pauwelsstrasse 30, D-52074 Aachen (Germany); Dinger, Cornelia; Zlatopolskiy, Boris D.; Al-Momani, Ehab; Glatting, Gerhard [Nuclear Medicine Clinic, University Ulm, Albert-Einstein-Allee 23, D-89081 Ulm (Germany); Mottaghy, Felix M. [Nuclear Medicine Clinic, University Aachen, RWTH, Pauwelsstrasse 30, D-52074 Aachen (Germany); Reske, Sven N. [Nuclear Medicine Clinic, University Ulm, Albert-Einstein-Allee 23, D-89081 Ulm (Germany)

    2011-10-15

    Introduction: Multiple myeloma (MM) is a plasma cell malignancy characterized by accumulation of malignant, terminally differentiated B cells in the bone marrow. Despite advances in therapy, MM remains an incurable disease. Novel therapeutic approaches are, therefore, urgently needed. Auger electron-emitting radiopharmaceuticals are attractive for targeted nano-irradiation therapy, given that DNA of malignant cells is selectively addressed. Here we evaluated the antimyeloma potential of the Auger electron-emitting thymidine analogue {sup 125}I-labeled 5-iodo-4'-thio-2'-deoxyuridine ([{sup 125}I]ITdU). Methods: Cellular uptake and DNA incorporation of [{sup 125}I]ITdU were determined in fluorodeoxyuridine-pretreated KMS12BM, U266, dexamethasone-sensitive MM1.S and -resistant MM1.R cell lines. The effect of stimulation with interleukin 6 (IL6) or insulin-like growth factor 1 (IGF1) on the intracellular incorporation of [{sup 125}I]ITdU was investigated in cytokine-sensitive MM1.S and MM1.R cell lines. Apoptotic cells were identified using Annexin V. Cleavage of caspase 3 and PARP was visualized by Western blot. DNA fragmentation was investigated using laddering assay. Therapeutic efficiency of [{sup 125}I]ITdU was proven by clonogenic assay. Results: [{sup 125}I]ITdU was shown to be efficiently incorporated into DNA of malignant cells, providing a promising mechanism for delivering highly toxic Auger radiation emitters into tumor DNA. [{sup 125}I]ITdU had a potent antimyeloma effect in cell lines representing distinct disease stages and, importantly, in cell lines sensitive or resistant to the conventional therapeutic agent, but was not toxic for normal plasma and bone marrow stromal cells. Furthermore, [{sup 125}I]ITdU abrogated the protective actions of IL6 and IGF1 on MM cells. [{sup 125}I]ITdU induced massive damage in the DNA of malignant plasma cells, which resulted in efficient inhibition of clonogenic growth. Conclusion: These studies may provide a

  2. WE-E-BRE-08: Impact of IUdR in Rat 9L Glioma Cell Survival for 25–35 KeV Photo-Activated Auger Electron Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, D; Hogstrom, K [Louisiana State University, Baton Rouge, LA (United States); Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Brown, T; Dugas, J; Varnes, M [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Matthews, K [Louisiana State University, Baton Rouge, LA (United States)

    2014-06-15

    Purpose: To determine the biological effect from Auger electrons with 9% and 18% iododeoxyuridine (IUdR) incorporated into the DNA of rat 9L glioma cells at photon energies above and below the K-edge of iodine (33.2 keV). Methods: Rat 9L glioma cell survival versus dose curves with 0%, 9%, and 18% thymidine replacement with IUdR were measured using four irradiation energies (4 MV x-rays; monochromatic 35, 30, and 25 keV synchrotron photons). For each of 11 conditions (Energy, %IUdR) survival curves were fit to the data (826 cell cultures) using the linear-quadratic model. The ratio of doses resulting in 10% survival gave sensitization enhancement ratios (SER10) from which contributions due to linear-energy transfer (LET), radiosensitization (RS), and Auger effect (AE) were extracted. Results: At 35, 30, and 25 keV, SER10,LET values were 1.08±0.03, 1.22±0.02, and 1.37±0.02, respectively. At 4 MV SER10,RS values for 9% and 18% IUdR were 1.28±0.02 and 1.40±0.02, respectively. Assuming LET effects are independent of %IUdR and radiosensitization effects are independent of energy, SER10,AE values for 18% IUdR at 35, 30, and 25 keV were 1.35±0.05, 1.06±0.03, and 0.98±0.03, respectively; values for 9% IUdR at 35 and 25 keV were 1.01±0.04 and 0.82±0.02, respectively. Conclusion: For 18% IUdR the radiosensitization effect of 1.40 and the Auger effect of 1.35 at 35 keV are equally important to the combined effect of 1.90. No measureable Auger effect was observed for energies below the K-edge at 20 and 25 keV, as expected. The insignificant Auger effect at 9% IUdR was not expected. Additional data (40–70 keV) and radiobiological modeling are being acquired to better understand the energy dependence of Auger electron therapy with IUdR. Funding support in part by the National Science Foundation Graduate Research Fellowship Program and in part by Contract No. W81XWH-10-1-0005 awarded by the U.S. Army Research Acquisition Activity. This paper does not necessarily

  3. Positron lifetime measurements and positron-annihilation induced auger electron spectroscpy using slow positron beams; Teisoku yodenshi bimu wo mochiita yodenshi jumyo sokutei oyobi yodenshi shometsu reiki oje denshi bunko

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, R. [Electrotechnical Lab., Tsukuba (Japan)

    1996-02-20

    Slow positron beam with less than several eV can be controlled freely such as accelerating, throttling the beam size, shortening the pulse or making pulse with short time width and so forth. These low positron beams are applied to various measurements like Doppler broadening measurement of annihilation {gamma} rays or lifetime measurement of positron, and secondary particle measurements using positron microscope, positron electron ray diffraction, flight time method and so forth. In particular, these recent years, high intensity slow positron beams were possible using accelerators like electron linac and its application is increasing. In this report, pulse shortening method for high intensity slow positron beam, and incidence energy variable positron lifetime measurement method using this slow pulsed beam and flight time type positron-annihilation-induced auger electron spectroscopy are outlined. In future, these measurements can be possible to carry out with high resolution and also with high counting rate if higher intensity monochromatic excellent positron beam than present one is produced. 31 refs., 5 figs.

  4. The hydroxylation of passive oxide films on X-70 steel by dissolved hydrogen studied by nuclear reaction analysis, Auger electron spectroscopy, X-ray photoelectron spectroscopy and secondary ion mass spectroscopy

    International Nuclear Information System (INIS)

    Zhang Chunsi; Luo Jingli; Munoz-Paniagua, David; Norton, Peter R.

    2006-01-01

    Dissolved hydrogen is known to reduce the corrosion resistance of a passive oxide film on iron and its alloys, especially towards pitting corrosion. Electrochemical techniques have been used to show that the passive films are changed by dissolved hydrogen in an alloy substrate, but direct confirmation of the chemical and compositional profiles and changes has been missing. In this paper we report the direct profiling and compositional analysis of the 4 nm passive film on X-70 steel by Auger electron spectroscopy (AES), secondary ion mass spectrometry (SIMS), X-ray photoelectron spectroscopy (XPS) and nuclear reaction analysis (NRA) while hydrogen (deuterium) is charged into the alloy samples from the reverse, unpassivated side. The only route for D to the passive film is therefore by dissolution and diffusion. We show that the original duplex structure of the passive film is converted to a more continuous film containing hydroxyl groups, by reaction with the dissolved hydrogen. This conversion of the oxide ions to hydroxyl groups can lead to more rapid reaction and replacement with (e.g.) Cl - , which is known to enhance pitting. These results are entirely consistent with previous electrochemical studies and provide the first direct confirmation of models on the formation and role of hydroxyl groups derived from these earlier studies

  5. Auger electron spectroscopy study of surface segregation in the binary alloys copper-1 atomic percent indium, copper-2 atomic percent tin, and iron-6.55 atomic percent silicon

    Science.gov (United States)

    Ferrante, J.

    1973-01-01

    Auger electron spectroscopy was used to examine surface segregation in the binary alloys copper-1 at. % indium, copper-2 at. % tin and iron-6.55 at. % silicon. The copper-tin and copper-indium alloys were single crystals oriented with the /111/ direction normal to the surface. An iron-6.5 at. % silicon alloy was studied (a single crystal oriented in the /100/ direction for study of a (100) surface). It was found that surface segregation occurred following sputtering in all cases. Only the iron-silicon single crystal alloy exhibited equilibrium segregation (i.e., reversibility of surface concentration with temperature) for which at present we have no explanation. McLean's analysis for equilibrium segregation at grain boundaries did not apply to the present results, despite the successful application to dilute copper-aluminum alloys. The relation of solute atomic size and solubility to surface segregation is discussed. Estimates of the depth of segregation in the copper-tin alloy indicate that it is of the order of a monolayer surface film.

  6. Estrogen, Estrogen Receptor and Lung Cancer

    Directory of Open Access Journals (Sweden)

    Li-Han Hsu

    2017-08-01

    Full Text Available Estrogen has been postulated as a contributor for lung cancer development and progression. We reviewed the current knowledge about the expression and prognostic implications of the estrogen receptors (ER in lung cancer, the effect and signaling pathway of estrogen on lung cancer, the hormone replacement therapy and lung cancer risk and survival, the mechanistic relationship between the ER and the epidermal growth factor receptor (EGFR, and the relevant clinical trials combining the ER antagonist and the EGFR antagonist, to investigate the role of estrogen in lung cancer. Estrogen and its receptor have the potential to become a prognosticator and a therapeutic target in lung cancer. On the other hand, tobacco smoking aggravates the effect of estrogen and endocrine disruptive chemicals from the environment targeting ER may well contribute to the lung carcinogenesis. They have gradually become important issues in the course of preventive medicine.

  7. Estrogens and aging skin

    OpenAIRE

    Thornton, M. Julie

    2013-01-01

    Estrogen deficiency following menopause results in atrophic skin changes and acceleration of skin aging. Estrogens significantly modulate skin physiology, targeting keratinocytes, fibroblasts, melanocytes, hair follicles and sebaceous glands, and improve angiogenesis, wound healing and immune responses. Estrogen insufficiency decreases defense against oxidative stress; skin becomes thinner with less collagen, decreased elasticity, increased wrinkling, increased dryness and reduced vascularity...

  8. The human polynucleotide kinase/phosphatase (hPNKP) inhibitor A12B4C3 radiosensitizes human myeloid leukemia cells to Auger electron-emitting anti-CD123 111In-NLS-7G3 radioimmunoconjugates

    International Nuclear Information System (INIS)

    Zereshkian, Arman; Leyton, Jeffrey V.; Cai, Zhongli; Bergstrom, Dane; Weinfeld, Michael; Reilly, Raymond M.

    2014-01-01

    Introduction: Leukemia stem cells (LSCs) are believed to be responsible for initiating and propagating acute myeloid leukemia (AML) and for causing relapse after treatment. Radioimmunotherapy (RIT) targeting these cells may improve the treatment of AML, but is limited by the low density of target epitopes. Our objective was to study a human polynucleotide kinase/phosphatase (hPNKP) inhibitor that interferes with DNA repair as a radiosensitizer for the Auger electron RIT agent, 111 In-NLS-7G3, which recognizes the CD123 + /CD131 - phenotype uniquely displayed by LSCs. Methods: The surviving fraction (SF) of CD123 + /CD131 - AML-5 cells exposed to 111 In-NLS-7G3 (33–266 nmols/L; 0.74 MBq/μg) or to γ-radiation (0.25-5 Gy) was determined by clonogenic assays. The effect of A12B4C3 (25 μmols/L) combined with 111 In-NLS-7G3 (16–66 nmols/L) or with γ-radiation (0.25–2 Gy) on the SF of AML-5 cells was assessed. The density of DNA double-strand breaks (DSBs) in the nucleus was measured using the γ-H2AX assay. Cellular dosimetry was estimated based on the subcellular distribution of 111 In-NLS-7G3 measured by cell fractionation. Results: Binding of 111 In-NLS-7G3 to AML-5 cells was reduced by 2.2-fold in the presence of an excess (1 μM) of unlabeled NLS-7G3, demonstrating specific binding to the CD123 + /CD131 - epitope. 111 In-NLS-7G3 reduced the SF of AML-5 cells from 86.1 ± 11.0% at 33 nmols/L to 10.5 ± 3.6% at 266 nmols/L. Unlabeled NLS-7G3 had no significant effect on the SF. Treatment of AML-5 cells with γ-radiation reduced the SF from 98.9 ± 14.9% at 0.25 Gy to 0.03 ± 0.1% at 5 Gy. A12B4C3 combined with 111 In-NLS-7G3 (16–66 nmols/L) enhanced the cytotoxicity up to 1.7-fold compared to treatment with radioimmunoconjugates alone and was associated with a 1.6-fold increase in DNA DSBs in the nucleus. A12B4C3 enhanced the cytotoxicity of γ-radiation (0.25–0.5 Gy) on AML-5 cells by up to 1.5-fold, and DNA DSBs were increased by 1.7-fold. Exposure to

  9. Effective applications of auger electron spectroscopy

    International Nuclear Information System (INIS)

    Golnabi, H.

    1996-01-01

    The goal of this study is to explore different aspects of the AES process and to present the new techniques which can be used effectively for analytical purposes. More emphasis is given to AES data acquisition, sensitivity factor and Auger intensity. The experimental details of a typical scanning Auger microprobe (SAM) is also presented. Applications of AES to selected systems such as microelectronic devices, superconductors, an in metallurgy are described

  10. Study on cell survival, induction of apoptosis and micronucleus formation in SCL-II and RTiV3 cells after exposure to the Auger electron emitter Tc-99m

    International Nuclear Information System (INIS)

    Kadenbach, K.; Kriehuber, R.; Weiss, D.G.

    2003-01-01

    Full text: Cell survival, induction of apoptosis and micronucleus (MN) formation have been investigated in the human squamous cell carcinoma cell line SCL-II and in the rat tracheal cell line RTiV3 after exposure to the Auger electron emitter Tc-99m. Cells were either acutely gamma(Co-60)-irradiated (0.78 Gy/min) or exposed to Tc-99m-Pertechnetate (25-300 MBq/20ml) for 24 h under cell culture conditions and assayed for cell survival (Colony-forming assay), micronucleus formation (Cytochalasin B assay) and the frequency of apoptotic cells (Fluorescence microscopy). Analytical dosimetrical models have been applied to derive the absorbed dose corresponding to the accumulated decays of Tc-99m. Absorbed doses up to 1.3 Gy could be achieved after Tc-99m exposure leading to no significant cell killing in this dose range except at one dose point (0.25 Gy) in SCL-II cells. MN formation was consistently lower when compared to Co-60 irradiated cells and showed a linear dose-response. The apoptotic response in SCL-II cells after Tc-99m exposure was described best by a 3rd order polynomial and increased apoptosis induction could be observed at much lower doses (0.25 Gy) in comparison to the reference radiation (0.8 Gy). The relative biological effectiveness (RBE) has been determined for MN formation and apoptosis induction and was found to be in the range of 0.1- 1.3 for both investigated biological endpoints, depending on which mathematical model for describing the dose-effect curve was used. Up-take experiments revealed an activity concentration ratio cells vs. medium of 1.2 after 16 h up to 24 h of exposure. No increased biological effectiveness of Tc-99m applied as Sodium-Pertechnetate could be observed in the investigated cell lines in comparison to gamma-irradiation. Induction of apoptosis is slightly increased after Tc-99m exposure in SCL-II cells and it has to be further evaluated, if this is due to the emitted Auger-component. A passive up-take mechanism of Tc-99m is

  11. Estrogens in breast cancer

    International Nuclear Information System (INIS)

    Terzieff, V.; Vázquez, A.

    2004-01-01

    The prolonged exposure to estrogen increases the risk of cancer breast, the precise role of estrogen in the carcinogenesis process is unclear. They are capable of inducing cell proliferation through different channels receptor Estrogen (ER) known, for example through MAPkinasa sensitivity the promoter of proliferation effect depends on the level of RE, or type to â, integrity (mutations may alter its function) and ligand. The different types of estrogens and related compounds have different profile of affinity for RE and effect end. The modulatory role of progestogens proliferation is very complex, and the interaction between the effector pathways of progestin’s, estrogens, EGF and IGF family - maybe others - determines the final effect .. Estrogens are mutagenic per se weak, but is now known for its hepatic metabolism occur highly reactive species such as quinones, and catechol, powerful mutagens in vitro. Direct or indirect genotoxicity probably explains Part of the effects of estrogen on tumor cells. The use of hormone replacement (HTR) increases the risk of CM, as proportional to the time of use. The combination with progestin seems to be increased risk (R R 2). It is unclear the role of phyto estrogens in the prevention the CM. In the male breast is known that the proliferative response to parenchymal different hormonal maneuvers is different. The effect is minimal castration are and maximum with the combination of estrogen and progesterone. It is unclear, however, the risk of the population exposed to hormone therapy for cancer prostate or otherwise

  12. Paradoxical effects of Auger electron-emitting 111In-DTPA-NLS-CSL360 radioimmunoconjugates on hCD45+ cells in the bone marrow and spleen of leukemia-engrafted NOD/SCID or NRG mice

    International Nuclear Information System (INIS)

    Bergstrom, Dane; Leyton, Jeffrey V.; Zereshkian, Arman; Chan, Conrad; Cai, Zhongli; Reilly, Raymond M.

    2016-01-01

    Introduction: 111 In-DTPA-NLS-CSL360 radioimmunoconjugates (RIC) recognize the overexpression of the interleukin-3 receptor α-subchain (CD123) relative to the β-subchain (CD131) on leukemia stem cells (LSC). Our aim was to study Auger electron radioimmunotherapy (RIT) of acute myeloid leukemia (AML) with 111 In-DTPA-NLS-CSL360 in non-obese diabetic severe combined immunodeficiency (NOD/SCID) mice or NOD-Rag1 null IL2rγ null (NRG) mice engrafted with CD123 + human AML-5 cells. Methods: The toxicity of three doses of 111 In-DTPA-NLS-CSL360 (3.3–4.8 MBq; 11–15 μg each) injected i.v. every two weeks was studied in non-engrafted NOD/SCID or NRG mice pre-treated with 200 cGy of γ-radiation required for AML engraftment. Engraftment efficiency of (1–5) × 10 6 cells AML-5 cells inoculated i.v. into NOD/SCID or NRG mice was assessed by flow cytometric analysis for human CD45 + (hCD45 + ) cells in the bone marrow (BM) and spleen. AML-5 engrafted mice were treated with two or three doses (3.7 MBq; 10 μg each) every two weeks of 111 In-DTPA-NLS-CSL360, non-specific 111 In-DTPA-NLS-hIgG, unlabeled CSL360 (10 μg) or normal saline. The percentage of hCD45 + cells in the BM and spleen were measured at one week after completion of treatment. Results: 111 In-DTPA-NLS-CSL360 in combination with 200 cGy of γ-radiation caused an initial transient decrease in body weight in NOD/SCID but not in NRG mice. There were no hematological, liver or kidney toxicities. The spleen exhibited 13-fold lower engraftment efficiency than the BM in NOD/SCID mice inoculated with 1 × 10 6 cells but both organs were highly (>85%) engrafted in NRG mice. Unexpectedly, 111 In-DTPA-NLS-CSL360 or non-specific 111 In-DTPA-NLS-hIgG caused a paradoxical 1.5-fold increase (P < 0.0001) in the proportion of hCD45 + cells in the BM of NOD/SCID mice compared to normal saline treated mice. 111 In-DTPA-NLS-CSL360 reduced hCD45 + cells in the spleen by 3.0-fold compared to 111 In-DTPA-NLS-hIgG (P = 0

  13. Anaerobic biotransformation of estrogens

    International Nuclear Information System (INIS)

    Czajka, Cynthia P.; Londry, Kathleen L.

    2006-01-01

    Estrogens are important environmental contaminants that disrupt endocrine systems and feminize male fish. We investigated the potential for anaerobic biodegradation of the estrogens 17-α-ethynylestradiol (EE2) and 17-β-estradiol (E2) in order to understand their fate in aquatic and terrestrial environments. Cultures were established using lake water and sediment under methanogenic, sulfate-, iron-, and nitrate-reducing conditions. Anaerobic degradation of EE2 (added at 5 mg/L) was not observed in multiple trials over long incubation periods (over three years). E2 (added at 5 mg/L) was transformed to estrone (E1) under all four anaerobic conditions (99-176 μg L -1 day -1 ), but the extent of conversion was different for each electron acceptor. The oxidation of E2 to E1 was not inhibited by E1. Under some conditions, reversible inter-conversion of E2 and E1 was observed, and the final steady state concentration of E2 depended on the electron-accepting condition but was independent of the total amount of estrogens added. In addition, racemization occurred and E1 was also transformed to 17-α-estradiol under all but nitrate-reducing conditions. Although E2 could be readily transformed to E1 and in many cases 17-α-estradiol under anaerobic conditions, the complete degradation of estrogens under these conditions was minimal, suggesting that they would accumulate in anoxic environments

  14. Estrogen and the female heart.

    Science.gov (United States)

    Knowlton, A A; Korzick, D H

    2014-05-25

    Estrogen has a plethora of effects in the cardiovascular system. Studies of estrogen and the heart span human clinical trials and basic cell and molecular investigations. Greater understanding of cell and molecular responses to estrogens can provide further insights into the findings of clinical studies. Differences in expression and cellular/intracellular distribution of the two main receptors, estrogen receptor (ER) α and β, are thought to account for the specificity and differences in responses to estrogen. Much remains to be learned in this area, but cellular distribution within the cardiovascular system is becoming clearer. Identification of GPER as a third ER has introduced further complexity to the system. 17β-estradiol (E2), the most potent human estrogen, clearly has protective properties activating a signaling cascade leading to cellular protection and also influencing expression of the protective heat shock proteins (HSP). E2 protects the heart from ischemic injury in basic studies, but the picture is more involved in the whole organism and clinical studies. Here the complexity of E2's widespread effects comes into play and makes interpretation of findings more challenging. Estrogen loss occurs primarily with aging, but few studies have used aged models despite clear evidence of differences between the response to estrogen deficiency in adult and aged animals. Thus more work is needed focusing on the effects of aging vs. estrogen loss on the cardiovascular system. Published by Elsevier Ireland Ltd.

  15. RNA Regulation of Estrogen

    Science.gov (United States)

    2010-08-01

    Berglund, Rodger Voelker, Paul Barber and Julien Diegel 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING...estrogen  receptors  [reviewed  in  (3,  4)],  also   functions   by  interacting  directly  with  RNA  to  alter  RNA...Mog myelin oligodendrocyte glycoprotein 6.06 207115_x_at mbtd1 mbt domain containing 1 6.06 208004_at Prol1 proline rich, lacrimal 1 6.06 205247_at

  16. Estrogen and gastrointestinal malignancy.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    The concept that E2 exerts an effect on the gastrointestinal tract is not new and its actions on intestinal mucosa have been investigated for at least three decades. An attempt to consolidate results of these investigations generates more questions than answers, thus suggesting that many unexplored avenues remain and that the full capabilities of this steroid hormone are far from understood. Evidence of its role in esophageal, gastric and gallbladder cancers is confusing and often equivocal. The most compelling evidence regards the protective role conferred by estrogen (or perhaps ERbeta) against the development and proliferation of colon cancer. Not only has the effect been described but also many mechanisms of action have been explored. It is likely that, along with surgery, chemotherapy and radiotherapy, hormonal manipulation will play an integral role in colon cancer management in the very near future.

  17. Mixture interactions of xenoestrogens with endogenous estrogens.

    Science.gov (United States)

    There is growing concern of exposure to fish, wildlife, and humans to water sources contaminated with estrogens and the potential impact on reproductive health. These environmental estrogens originate from various sources including concentrated animal feedlot operations (CAFO), m...

  18. Bonding of radioactive contamination. III. Auger electron spectroscopic investigation

    International Nuclear Information System (INIS)

    Rankin, W.N.; Whitkop, P.G.

    1983-01-01

    The mechanisms by which radioactive contamination would be bonded to a DWPF canister surface are being investigated. Tests with low pressure water and air-injected water decontamination of radioactive specimens showed that bonding of contamination increases rapidly with postoxidation temperature. Even with the least severe temperature conditions expected on the waste glass canister, bonding is so great that decontamination cannot be affected by water-only techniques. A preoxidation film increased rather than decreased bonding. This memorandum describes detailed surface analyses of coupons simulating DWPF canister surfaces. Based on this examination we conclude: contamination will be dispersed throughout the oxide film on DWPF canisters. Contamination is concentrated at the surface, decreasing farther into the oxide film; some samples contain sludge contamination at the steel/oxide interface. This was not the case for semi-volatile (Cs 2 O) contamination; in samples with contamination at the steel/oxide interface, at least 80% of the contamination is usually in the oxide layer; no difference in contamination dispersion between preoxidized and non-preoxidized samples was found; and postoxidation atmosphere had no effect on the contamination dispersion within the oxide layer. 6 references, 9 figures

  19. Auger electron spectroscopy, ionization loss spectroscopy, appearance potential spectroscopy

    International Nuclear Information System (INIS)

    Riwan, R.

    1973-01-01

    The spectroscopy of surfaces using an incident electron beam is studied. The fundamental mechanisms are discussed together with the parameters involved in Auger emission: excitation of the atom, de-excitation by electron emission, and the migration of electrons towards the surface and their ejection. Some examples of applications are given (surface structures, metallurgy, chemical information). Two new techniques for analyzing surfaces are studied: ionization spectroscopy, and appearance potential spectroscopy [fr

  20. Estrogenic and pregnancy interceptory effects of Achyranthes ...

    African Journals Online (AJOL)

    ... the dose of 200 mg/kg body weight also exhibited estrogenic activity. Histological studies of the uterus were carried out to confirm this estrogenic activity. Keywords: Achyranthes aspera; antifertility; anti-implantation; estrogenic; uterotropic. The African Journal of Traditional, Complementary and Alternative Medicines Vol.

  1. Mitochondria: Target organelles for estrogen action

    Directory of Open Access Journals (Sweden)

    Małgorzata Chmielewska

    2017-06-01

    Full Text Available Estrogens belong to a group of sex hormones, which have been shown to act in multidirectional way. Estrogenic effects are mediated by two types of intracellular receptors: estrogen receptor 1 (ESR1 and estrogen receptor 2 (ESR2. There are two basic mechanisms of estrogen action: 1 classical-genomic, in which the ligand-receptor complex acts as a transcriptional factor and 2 a nongenomic one, which is still not fully understood, but has been seen to lead to distinct biological effects, depending on tissue and ligand type. It is postulated that nongenomic effects may be associated with membrane signaling and the presence of classical nuclear receptors within the cell membrane. Estrogens act in a multidirectional way also within cell organelles. It is assumed that there is a mechanism which manages the migration of ESR into the mitochondrial membrane, wherein the exogenous estrogen affect the morphology of mitochondria. Estrogen, through its receptor, can directly modulate mitochondrial gene expression. Moreover, by regulating the level of reactive oxygen species, estrogens affect the biology of mitochondria. The considerations presented in this paper indicate the pleiotropic effects of estrogens, which represent a multidirectional pathway of signal transduction.

  2. Estrogen Treatment in Multiple Sclerosis

    OpenAIRE

    Gold, Stefan M; Voskuhl, Rhonda R

    2009-01-01

    Currently available treatments for multiple sclerosis reduce inflammatory lesions on MRI and decrease clinical relapses but have limited effects on disability. Novel treatment options that target both the inflammatory as well as the neurodegenerative component of the disease are therefore needed. A growing body of evidence from basic science and clinical studies supports the therapeutic potential of estrogens in MS. Mechanisms of action include both immunomodulatory and directly neuroprotecti...

  3. Distinct Effects of Estrogen on Mouse Maternal Behavior: The Contribution of Estrogen Synthesis in the Brain

    Science.gov (United States)

    Murakami, Gen

    2016-01-01

    Estrogen surge following progesterone withdrawal at parturition plays an important role in initiating maternal behavior in various rodent species. Systemic estrogen treatment shortens the latency to onset of maternal behavior in nulliparous female rats that have not experienced parturition. In contrast, nulliparous laboratory mice show rapid onset of maternal behavior without estrogen treatment, and the role of estrogen still remains unclear. Here the effect of systemic estrogen treatment (for 2 h, 1 day, 3 days, and 7 days) after progesterone withdrawal was examined on maternal behavior of C57BL/6 mice. This estrogen regimen led to different effects on nursing, pup retrieval, and nest building behaviors. Latency to nursing was shortened by estrogen treatment within 2 h. Moreover, pup retrieval and nest building were decreased. mRNA expression was also investigated for estrogen receptor α (ERα) and for genes involved in regulating maternal behavior, specifically, the oxytocin receptor (OTR) and vasopressin receptor in the medial amygdala (MeA) and medial preoptic area (MPOA). Estrogen treatment led to decreased ERα mRNA in both regions. Although OTR mRNA was increased in the MeA, OTR and vasopressin receptor mRNA were reduced in the MPOA, showing region-dependent transcription regulation. To determine the mechanisms for the actions of estrogen treatment, the contribution of estrogen synthesis in the brain was examined. Blockade of estrogen synthesis in the brain by systemic letrozole treatment in ovariectomized mice interfered with pup retrieval and nest building but not nursing behavior, indicating different contributions of estrogen synthesis to maternal behavior. Furthermore, letrozole treatment led to an increase in ERα mRNA in the MeA but not in the MPOA, suggesting that involvement of estrogen synthesis is brain region dependent. Altogether, these results suggest that region-dependent estrogen synthesis leads to differential transcriptional activation due

  4. Estrogenic activity, estrogens, and calcium in runoff post-layer litter application from rainfall simulated events

    Science.gov (United States)

    Estrogens in runoff from fields fertilized with animal wastes have been implicated as endocrine disruptors of fish in recipient surface waters. The goal of this study was to measure estrogenic activity in runoff post-application of animal waste with the greatest potential for estrogenic activity - ...

  5. CERAPP: Collaborative Estrogen Receptor Activity Prediction Project

    Data.gov (United States)

    U.S. Environmental Protection Agency — Data from a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) demonstrating using predictive computational...

  6. Estrogens and Cognition: Friends or Foes?

    Science.gov (United States)

    Korol, Donna L.; Pisani, Samantha L.

    2015-01-01

    Estrogens are becoming well known for their robust enhancement on cognition particularly for learning and memory that relies upon functioning of the hippocampus and related neural systems. What is also emerging is that estrogen modulation of cognition is not uniform, at times enhancing yet at other times impairing learning. This review explores the bidirectional effects of estrogens on learning from a multiple memory systems view, focusing on the hippocampus and striatum, whereby modulation by estrogens sorts according to task attributes and neural systems engaged during cognition. We highlight our findings that show the ability to solve hippocampus-sensitive tasks typically improves under relatively high estrogen status while the ability to solve striatum-sensitive tasks degrades with estrogen exposures. Though constrained by dose and timing of exposure, these opposing enhancements and impairments of cognition can be observed following treatments with different estrogenic compounds including the hormone estradiol, the isoflavone genistein found in soybeans, and agonists that are selective for specific estrogen receptors, suggesting that activation of a single receptor type is sufficient to produce the observed shifts in learning strategies. Using this multi-dimensional framework will allow us to extend our thinking of the relationship between estrogens and cognition to other brain regions and cognitive functions. PMID:26149525

  7. Impact of Estrogens and Estrogen Receptor Alpha (ESR1) in Brain Lipid Metabolism.

    Science.gov (United States)

    Morselli, Eugenia; de Souza Santos, Roberta; Gao, Su; Ávalos, Yenniffer; Criollo, Alfredo; Palmer, Biff F; Clegg, Deborah J

    2018-03-06

    Estrogens and their receptors play key roles in regulating body weight, energy expenditure, and metabolic homeostasis. It is known that lack of estrogens promotes increased food intake and induces the expansion of adipose tissues, for which much is known. An area of estrogenic research that has received less attention is the role of estrogens and their receptors in influencing intermediary lipid metabolism in organs such as the brain. In this review, we highlight the actions of estrogens and their receptors in regulating their impact on modulating fatty acid content, utilization, and oxidation through their direct impact on intracellular signaling cascades within the central nervous system.

  8. Estrogen induces glomerulosclerosis in analbuminemic rats

    NARCIS (Netherlands)

    Joles, JA; van Goor, H; Koomans, HA

    Progression of chronic renal disease: is usually more rapid in males, both In humans and in experimental animals. Estrogen-replacement studies indicate that this may be related to the beneficial effects of estrogen on the lipoprotein profile. However, in hyperlipidemic analbuminemic rats (NAR),

  9. Quantum chemical studies of estrogenic compounds

    Science.gov (United States)

    Quantum chemical methods are potent tools to provide information on the chemical structure and electronic properties of organic molecules. Modern computational chemistry methods have provided a great deal of insight into the binding of estrogenic compounds to estrogenic receptors (ER), an important ...

  10. Labeled estrogens as mammary tumor probes

    International Nuclear Information System (INIS)

    Feenstra, A.

    1981-01-01

    In this thesis estrogens labeled with a gamma or positron emitting nuclide, called estrogen-receptor binding radiopharmaceuticals are investigated as mammary tumour probes. The requirements for estrogen-receptor binding radiopharmaceuticals are formulated and the literature on estrogens labeled for this purpose is reviewed. The potential of mercury-197/197m and of carbon-11 as label for estrogen-receptor binding radiopharmaceuticals is investigated. The synthesis of 197 Hg-labeled 4-mercury-estradiol and 2-mercury-estradiol and their properties in vitro and in vivo are described. It appears that though basically carbon-11 labeled compounds are very promising as mammary tumour probes, their achievable specific activity has to be increased. (Auth.)

  11. Endoxifen, 4-Hydroxytamoxifen and an Estrogenic Derivative Modulate Estrogen Receptor Complex Mediated Apoptosis in Breast Cancer.

    Science.gov (United States)

    Maximov, Philipp Y; Abderrahman, Balkees; Fanning, Sean W; Sengupta, Surojeet; Fan, Ping; Curpan, Ramona F; Quintana Rincon, Daniela Maria; Greenland, Jeffery A; Rajan, Shyamala S; Greene, Geoffrey L; Jordan, V Craig

    2018-05-08

    Estrogen therapy was used to treat advanced breast cancer in postmenopausal women for decades until the introduction of tamoxifen. Resistance to long-term estrogen deprivation (LTED) with tamoxifen and aromatase inhibitors used as a treatment for breast cancer inevitably occurs, but unexpectedly low dose estrogen can cause regression of breast cancer and increase disease free survival in some patients. This therapeutic effect is attributed to estrogen-induced apoptosis in LTED breast cancer. Here we describe modulation of the estrogen receptor liganded with antiestrogens (endoxifen, 4-hydroxytamoxifen) and an estrogenic triphenylethylene (TPE) EthoxyTPE (EtOXTPE) on estrogen-induced apoptosis in LTED breast cancer cells. Our results show that the angular TPE estrogen (EtOXTPE) is able to induce the ER-mediated apoptosis only at a later time compared to planar estradiol in these cells. Using RT-PCR, ChIP, Western blotting, molecular modelling and X-ray crystallography techniques we report novel conformations of the ER complex with an angular estrogen EtOXTPE and endoxifen. We propose that alteration of the conformation of the ER complexes, with changes in coactivator binding, governs estrogen-induced apoptosis through the PERK sensor system to trigger an Unfolded Protein Response (UPR). The American Society for Pharmacology and Experimental Therapeutics.

  12. Effects of environmental estrogenic chemicals on AP1 mediated transcription with estrogen receptors alpha and beta.

    Science.gov (United States)

    Fujimoto, Nariaki; Honda, Hiroaki; Kitamura, Shigeyuki

    2004-01-01

    There has been much discussion concerning endocrine disrupting chemicals suspected of exerting adverse effects in both wildlife and humans. Since the majority of these compounds are estrogenic, a large number of in vitro tests for estrogenic characteristics have been developed for screening purpose. One reliable and widely used method is the reporter gene assay employing estrogen receptors (ERs) and a reporter gene with a cis-acting estrogen responsive element (ERE). Other elements such as AP1 also mediate estrogenic signals and the manner of response could be quite different from that of ERE. Since this has yet to be explored, the ER mediated AP1 activity in response to a series of environmental estrogens was investigated in comparison with ERE findings. All the compounds exhibited estrogenic properties with ERE-luc and their AP1 responses were quite similar. These was one exception, however, p,p'-DDT (1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane) did not exert any AP1-luc activity, while it appeared to be estrogenic at 10(-7) to 10(-5)M with the ERE action. None of the compounds demonstrated ER beta:AP1 activity. These data suggest that significant differences can occur in responses through the two estrogen pathways depending on environmental chemicals.

  13. In Vivo Anti-estrogenic Effects of Menadione on Hepatic Estrogen-responsive Gene Expression in Male Medaka (Oryzias latipes)

    OpenAIRE

    Yamaguchi, Akemi; Kohra, Shinya; Ishibashi, Hiroshi; Arizono, Koji; Tominaga, Nobuaki

    2008-01-01

    Menadione, a synthetic vitamin K3, exhibits anti-estrogenic activity on in vitro assay. However, the in vivo anti-estrogenic effects of menadione have not been determined, while correlations between biological effects and structural changes are unclear. Thus, we investigated the in vivo anti-estrogenic activity of menadione under fluorescent light and dark conditions. Suppression of the hepatic estrogen response genes vitellogenin1 (VTG1), VTG2 and estrogen receptor-α (ER-α) was used as an in...

  14. Breast Cancer and Estrogen-Alone Update

    Science.gov (United States)

    ... Current Issue Past Issues Research News From NIH Breast Cancer and Estrogen-Alone Update Past Issues / Summer 2006 ... hormone therapy does not increase the risk of breast cancer in postmenopausal women, according to an updated analysis ...

  15. Estrogens and progression of diabetic kidney damage.

    Science.gov (United States)

    Doublier, Sophie; Lupia, Enrico; Catanuto, Paola; Elliot, Sharon J

    2011-01-01

    It is generally accepted that estrogens affect and modulate the development and progression of chronic kidney diseases (CKD) not related to diabetes. Clinical studies have indeed demonstrated that the severity and rate of progression of renal damage tends to be greater among men, compared with women. Experimental studies also support the notion that female sex is protective and male sex permissive, for the development of CKD in non-diabetics, through the opposing actions of estrogens and testosterone. However, when we consider diabetes-induced kidney damage, in the setting of either type 1 or type 2 diabetes, the contribution of gender to the progression of renal disease is somewhat uncertain. Previous studies on the effects of estrogens in the pathogenesis of progressive kidney damage have primarily focused on mesangial cells. More recently, data on the effects of estrogens on podocytes, the cell type whose role may include initiation of progressive diabetic renal disease, became available. The aim of this review will be to summarize the main clinical and experimental data on the effects of estrogens on the progression of diabetes-induced kidney injury. In particular, we will highlight the possible biological effects of estrogens on podocytes, especially considering those critical for the pathogenesis of diabetic kidney damage.

  16. Estrogen enhances mismatch repair by induction of MLH1 expression via estrogen receptor-β.

    Science.gov (United States)

    Lu, Jun-Yu; Jin, Peng; Gao, Wei; Wang, De-Zhi; Sheng, Jian-Qiu

    2017-06-13

    Epidemiological data demonstrated that hormone replace treatment has protective effect against colorectal cancer (CRC). Our previous studies showed that this effect may be associated with DNA mismatch repair. This study aims to investigate the mechanism of estrogen induction of MLH1, and whether colorectal tumor proliferation can be inhibited through induction of MLH1 by estrogen signal pathway. Human CRC cell lines were used to examine the regulation of MLH1 expression by over-expression and depletion of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ), under the treatment with 17β-estradiol or β-Estradiol 6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and Western blotting analysis. Luciferase reporter and chromatin immunoprecipitation assays were used to identify the estrogen response elements in the proximal promoter of MLH1 gene. Then, the influence of estrogen-induced MLH1 on CRC tumor growth were determined in vitro and in vivo. We found that mismatch repair ability and microsatellite stability of cells were enhanced by estrogen via induction of MLH1 expression, which was mediated by ERβ, through a transcriptional activation process. Furthermore, we identified that ERβ exerted an inhibitory effect on CRC tumor proliferation in vitro and in vivo, combined with 5-FU, through up-regulation of MLH1 expression. Finally, we concluded that estrogen enhances mismatch repair ability and tumor inhibition effect in vitro and in vivo, via induction of MLH1 expression mediated by ERβ.

  17. Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study.

    Science.gov (United States)

    Flores, Roberto; Shi, Jianxin; Fuhrman, Barbara; Xu, Xia; Veenstra, Timothy D; Gail, Mitchell H; Gajer, Pawel; Ravel, Jacques; Goedert, James J

    2012-12-21

    High systemic estrogen levels contribute to breast cancer risk for postmenopausal women, whereas low levels contribute to osteoporosis risk. Except for obesity, determinants of non-ovarian systemic estrogen levels are undefined. We sought to identify members and functions of the intestinal microbial community associated with estrogen levels via enterohepatic recirculation. Fifty-one epidemiologists at the National Institutes of Health, including 25 men, 7 postmenopausal women, and 19 premenopausal women, provided urine and aliquots of feces, using methods proven to yield accurate and reproducible results. Estradiol, estrone, 13 estrogen metabolites (EM), and their sum (total estrogens) were quantified in urine and feces by liquid chromatography/tandem mass spectrometry. In feces, β-glucuronidase and β-glucosidase activities were determined by realtime kinetics, and microbiome diversity and taxonomy were estimated by pyrosequencing 16S rRNA amplicons. Pearson correlations were computed for each loge estrogen level, loge enzymatic activity level, and microbiome alpha diversity estimate. For the 55 taxa with mean relative abundance of at least 0.1%, ordinal levels were created [zero, low (below median of detected sequences), high] and compared to loge estrogens, β-glucuronidase and β-glucosidase enzymatic activity levels by linear regression. Significance was based on two-sided tests with α=0.05. In men and postmenopausal women, levels of total urinary estrogens (as well as most individual EM) were very strongly and directly associated with all measures of fecal microbiome richness and alpha diversity (R≥0.50, P≤0.003). These non-ovarian systemic estrogens also were strongly and significantly associated with fecal Clostridia taxa, including non-Clostridiales and three genera in the Ruminococcaceae family (R=0.57-0.70, P=0.03-0.002). Estrone, but not other EM, in urine correlated significantly with functional activity of fecal β-glucuronidase (R=0.36, P=0

  18. Estrogen receptor-independent catechol estrogen binding activity: protein binding studies in wild-type, Estrogen receptor-alpha KO, and aromatase KO mice tissues.

    Science.gov (United States)

    Philips, Brian J; Ansell, Pete J; Newton, Leslie G; Harada, Nobuhiro; Honda, Shin-Ichiro; Ganjam, Venkataseshu K; Rottinghaus, George E; Welshons, Wade V; Lubahn, Dennis B

    2004-06-01

    Primary evidence for novel estrogen signaling pathways is based upon well-documented estrogenic responses not inhibited by estrogen receptor antagonists. In addition to 17beta-E2, the catechol estrogen 4-hydroxyestradiol (4OHE2) has been shown to elicit biological responses independent of classical estrogen receptors in estrogen receptor-alpha knockout (ERalphaKO) mice. Consequently, our research was designed to biochemically characterize the protein(s) that could be mediating the biological effects of catechol estrogens using enzymatically synthesized, radiolabeled 4-hydroxyestrone (4OHE1) and 4OHE2. Scatchard analyses identified a single class of high-affinity (K(d) approximately 1.6 nM), saturable cytosolic binding sites in several ERalphaKO estrogen-responsive tissues. Specific catechol estrogen binding was competitively inhibited by unlabeled catechol estrogens, but not by 17beta-E2 or the estrogen receptor antagonist ICI 182,780. Tissue distribution studies indicated significant binding differences both within and among various tissues in wild-type, ERalphaKO, and aromatase knockout female mice. Ligand metabolism experiments revealed extensive metabolism of labeled catechol estrogen, suggesting that catechol estrogen metabolites were responsible for the specific binding. Collectively, our data provide compelling evidence for the interaction of catechol estrogen metabolites with a novel binding protein that exhibits high affinity, specificity, and selective tissue distribution. The extensive biochemical characterization of this binding protein indicates that this protein may be a receptor, and thus may mediate ERalpha/beta-independent effects of catechol estrogens and their metabolites.

  19. Estrogenicity of glabridin in Ishikawa cells.

    Directory of Open Access Journals (Sweden)

    Melissa Su Wei Poh

    Full Text Available Glabridin is an isoflavan from licorice root, which is a common component of herbal remedies used for treatment of menopausal symptoms. Past studies have shown that glabridin resulted in favorable outcome similar to 17β-estradiol (17β-E2, suggesting a possible role as an estrogen replacement therapy (ERT. This study aims to evaluate the estrogenic effect of glabridin in an in-vitro endometrial cell line -Ishikawa cells via alkaline phosphatase (ALP assay and ER-α-SRC-1-co-activator assay. Its effect on cell proliferation was also evaluated using Thiazoyl blue tetrazolium bromide (MTT assay. The results showed that glabridin activated the ER-α-SRC-1-co-activator complex and displayed a dose-dependent increase in estrogenic activity supporting its use as an ERT. However, glabridin also induced an increase in cell proliferation. When glabridin was treated together with 17β-E2, synergistic estrogenic effect was observed with a slight decrease in cell proliferation as compared to treatment by 17β-E2 alone. This suggest that the combination might be better suited for providing high estrogenic effects with lower incidences of endometrial cancer that is associated with 17β-E2.

  20. Aromatase and estrogen receptors in male reproduction.

    Science.gov (United States)

    Carreau, Serge; Delalande, Christelle; Silandre, Dorothée; Bourguiba, Sonia; Lambard, Sophie

    2006-02-26

    Aromatase is a terminal enzyme which transforms irreversibly androgens into estrogens and it is present in the endoplasmic reticulum of numerous tissues. We have demonstrated that mature rat germ cells express a functional aromatase with a production of estrogens equivalent to that of Leydig cells. In humans in addition to Leydig cells, we have shown the presence of aromatase in ejaculated spermatozoa and in immature germ cells. In most tissues, high affinity estrogen receptors, ERalpha and/or ERbeta, mediate the role of estrogens. Indeed, in human spermatozoa, we have successfully amplified ERbeta mRNA but the protein was not detectable. Using ERalpha antibody we have detected two proteins in human immature germ cells: one at the expected size 66 kDa and another at 46 kDa likely corresponding to the ERalpha isoform lacking exon 1. In spermatozoa only the 46 kDa isoform was present, and we suggest that it may be located on the membrane. In addition, in men genetically deficient in aromatase, it is reported that alterations of spermatogenesis occur both in terms of the number and motility of spermatozoa. All together, these observations suggest that endogenous estrogens are important in male reproduction.

  1. Pollution by endocrine disrupting estrogens in aquatic ecosystems ...

    African Journals Online (AJOL)

    Jane Erike-Etchie

    reproductive abnormalities than the natural estrogens. (Aris et al., 2014). .... 2006; Pool, 2008). Detection and quantification of estrogens by ELISA competitive ..... Williams M, Wood M, Kumar A, Ying GG, Shareef A, Karkkainen M,. Kookana R ...

  2. The role of estrogen in bipolar disorder, a review

    DEFF Research Database (Denmark)

    Meinhard, Ninja; Kessing, Lars Vedel; Vinberg, Maj

    2014-01-01

    hormones, e.g. estrogen, are fluctuating and particularly postpartum there is a steep fall in the levels of serum estrogen. The role of estrogen in women with bipolar disorder is, however, not fully understood. Aim: The main objective of this review is to evaluate the possible relation between serum...... estrogen levels and women with bipolar disorder including studies of the anti manic effects of the selective estrogen receptor modulator tamoxifen. Method: A systematically literature search on PubMed was conducted: two studies regarding the connection between serum estrogen levels and women with bipolar...... tamoxifen studies found that tamoxifen was effective in producing antimanic effects. Conclusion: These results indicate that estrogen fluctuations may be an important factor in the etiology of bipolar disorder and it is obvious that more research on this topic is needed to clarify the role of estrogen...

  3. The role of estrogen in bipolar disorder, a review

    DEFF Research Database (Denmark)

    Meinhard, Ninja; Kessing, Lars Vedel; Vinberg, Maj

    2014-01-01

    hormones, e.g. estrogen, are fluctuating and particularly postpartum there is a steep fall in the levels of serum estrogen. The role of estrogen in women with bipolar disorder is, however, not fully understood. AIM: The main objective of this review is to evaluate the possible relation between serum...... estrogen levels and women with bipolar disorder including studies of the anti manic effects of the selective estrogen receptor modulator tamoxifen. METHOD: A systematically literature search on PubMed was conducted: two studies regarding the connection between serum estrogen levels and women with bipolar...... tamoxifen studies found that tamoxifen was effective in producing antimanic effects. CONCLUSION: These results indicate that estrogen fluctuations may be an important factor in the etiology of bipolar disorder and it is obvious that more research on this topic is needed to clarify the role of estrogen...

  4. Classical and Nonclassical Estrogen Receptor Action on Chromatin Templates

    National Research Council Canada - National Science Library

    Nordeen, Steven

    2000-01-01

    .... Using newly-developed approaches, I investigated mechanisms of estrogen/estrogen receptor action on chromatin templates in vitro in order to better understand the role of chromatin in steroid-regulated gene expression...

  5. Classical and Nonclassical Estrogen Receptor Action on Chromatin Templaces

    National Research Council Canada - National Science Library

    Nordeen, Steve

    2001-01-01

    .... Using newly-developed approaches, I investigated mechanisms of estrogen/estrogen receptor action on chromatin templates in vitro in order to better understand the role of chromatin in steroid-regulated gene expression...

  6. Use of vaginal estrogen in Danish women

    DEFF Research Database (Denmark)

    Meaidi, Amani; Goukasian, Irina; Lidegaard, Oejvind

    2016-01-01

    INTRODUCTION: We know little about the use of vaginal estrogen in perimenopausal and postmenopausal women. We aimed to assess the prevalence of vaginal estrogen use in Denmark. MATERIAL AND METHODS: The study was designed as a nationwide cross-sectional study of all Danish women aged 40-79 years......, living in Denmark during the period 2007-2013. The Danish Prescription Register delivered data permitting us to assess the prevalence, age and regional geographical belonging of women purchasing prescribed vaginal estradiol. The number of women using over-the-counter vaginal estriol products...... was estimated from sale statistics from the same register. RESULTS: In 2013, 10.2% of all Danish women between 40 and 79 years of age used vaginal estradiol. The prevalence of women using this type of vaginal estrogen increased from 8.5% in year 2007 to 10.2% in 2013. The use peaked at 16.5% in women aged 60...

  7. Estrogen-associated severe hypertriglyceridemia with pancreatitis.

    Science.gov (United States)

    Aljenedil, Sumayah; Hegele, Robert A; Genest, Jacques; Awan, Zuhier

    Estrogen, whether therapeutic or physiologic, can cause hypertriglyceridemia. Hypertriglyceridemia-induced pancreatitis is a rare complication. We report 2 women who developed estrogen-associated severe hypertriglyceridemia with pancreatitis. The first patient developed pancreatitis secondary to hypertriglyceridemia associated with in vitro fertilization cycles. Marked reduction in her triglyceride was achieved with dietary restrictions and fibrate. The second patient developed pancreatitis secondary to hypertriglyceridemia during her pregnancies. She was noncompliant with the treatment; therefore, her triglyceride remained high after delivery. In both patients, no hypertriglyceridemia-associated genes mutations were identified, although the second patient had strong polygenic susceptibility to hypertriglyceridemia. Estrogen-induced severe hypertriglyceridemia with pancreatitis can be a life-threatening condition. Screening in high-risk patients is crucial to prevent subsequent complications. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  8. Membrane estrogen receptors - is it an alternative way of estrogen action?

    Science.gov (United States)

    Soltysik, K; Czekaj, P

    2013-04-01

    The functions of estrogens are relatively well known, however the molecular mechanism of their action is not clear. The classical pathway of estrogen action is dependent on ERα and ERβ which act as transcription factors. The effects of this pathway occur within hours or days. In addition, so-called, non-classical mechanism of steroid action dependent on membrane estrogen receptors (mER) was described. In this mechanism the effects of estrogen action are observed in a much shorter time. Here we review the structure and cellular localization of mER, molecular basis of non-classical mER action, physiological role of mER as well as implications of mER action for cancer biology. Finally, some concerns about the new estrogen receptor - GPER and candidates for estrogen receptors - ER-X and ERx, are briefly discussed. It seems that mER is a complex containing signal proteins (signalosome), as IGF receptor, EGF receptor, Ras protein, adaptor protein Shc, non-receptor kinase c-Src and PI-3K, what rationalizes production of second messengers. Some features of membrane receptors are almost identical if compared to nuclear receptors. Probably, membrane and nuclear estrogen receptors are not separate units, but rather the components of a complex mechanism in which they both cooperate with each other. We conclude that the image of the estrogen receptor as a simple transcription factor is a far-reaching simplification. A better understanding of the mechanisms of estrogen action will help us to design more effective drugs affecting signal pathways depending on both membrane and nuclear receptors.

  9. Assessment of estrogenic activity in some common essential oil constituents.

    Science.gov (United States)

    Howes, M-J R; Houghton, P J; Barlow, D J; Pocock, V J; Milligan, S R

    2002-11-01

    Estrogenic responses have not only been associated with endocrine function, but also with cognitive function. Several studies have indicated that estrogen replacement therapy has favourable effects on cognition, and may have potential in the prevention and treatment of Alzheimer's disease. Thus, ligands for the estrogen receptor, that have a better efficacy and adverse-effect profile than drugs currently available, require investigation. This study was undertaken to investigate the potential estrogenic activity of a number of essential oil constituents. Initially, estrogenic activity was determined by a sensitive and specific bioassay using recombinant yeast cells expressing the human estrogen receptor. At high concentrations, estrogenic activity was detected for citral (geranial and neral), geraniol, nerol and trans-anethole, while eugenol showed anti-estrogenic activity. Molecular graphics studies were undertaken to identify the possible mechanisms for the interaction of geranial, neral, geraniol, nerol and eugenol with the ligand-binding domain of the estrogen alpha-receptor, using the computer program HyperChem. Citral, geraniol, nerol and eugenol were also able to displace [(3)H]17beta-estradiol from isolated alpha- and beta-human estrogen receptors, but none of these compounds showed estrogenic or anti-estrogenic activity in the estrogen-responsive human cell line Ishikawa Var I at levels below their cytotoxic concentrations, and none showed activity in a yeast screen for androgenic and anti-androgenic activity. The potential in-vivo estrogenic effects of citral and geraniol were examined in ovariectomized mice, but neither compound showed any ability to stimulate the characteristic estrogenic responses of uterine hypertrophy or acute increase in uterine vascular permeability. These results show that very high concentrations of some commonly used essential oil constituents appear to have the potential to interact with estrogen receptors, although the

  10. Vascular measurements correlate with estrogen receptor status

    International Nuclear Information System (INIS)

    Lloyd, Mark C; Alfarouk, Khalid O; Verduzco, Daniel; Bui, Marilyn M; Gillies, Robert J; Ibrahim, Muntaser E; Brown, Joel S; Gatenby, Robert A

    2014-01-01

    Breast carcinoma can be classified as either Estrogen Receptor (ER) positive or negative by immunohistochemical phenotyping, although ER expression may vary from 1 to 100% of malignant cells within an ER + tumor. This is similar to genetic variability observed in other tumor types and is generally viewed as a consequence of intratumoral evolution driven by random genetic mutations. Here we view cellular evolution within tumors as a classical Darwinian system in which variations in molecular properties represent predictable adaptations to spatially heterogeneous environmental selection forces. We hypothesize that ER expression is a successful adaptive strategy only if estrogen is present in the microenvironment. Since the dominant source of estrogen is blood flow, we hypothesized that, in general, intratumoral regions with higher blood flow would contain larger numbers of ER + cells when compared to areas of low blood flow and in turn necrosis. This study used digital pathology whole slide image acquisition and advanced image analysis algorithms. We examined the spatial distribution of ER + and ER- cells, vascular density, vessel area, and tissue necrosis within histological sections of 24 breast cancer specimens. These data were correlated with the patients ER status and molecular pathology report findings. ANOVA analyses revealed a strong correlation between vascular area and ER expression and between high fractional necrosis and absent ER expression (R 2 = 39%; p < 0.003 and R 2 = 46%; p < 0.001), respectively). ER expression did not correlate with tumor grade or size. We conclude that ER expression can be understood as a Darwinian process and linked to variations in estrogen delivery by temporal and spatial heterogeneity in blood flow. This correlation suggests strategies to promote intratumoral blood flow or a cyclic introduction of estrogen in the treatment schedule could be explored as a counter-intuitive approach to increase the efficacy of anti-estrogen

  11. Estrogenic activity of flavonoids in mice. The importance of estrogen receptor distribution, metabolism and bioavailability

    DEFF Research Database (Denmark)

    Breinholt, Vibeke; Hossaini, A.; Svendsen, Gitte W.

    2000-01-01

    The in vivo estrogenic potential of the flavonoids apigenin, kaempferol, genistein and equol was investigated in immature female mice. Genistein and equol, administered by gavage for 4 consecutive days [post-natal day (PND) 17-20, 100 mg/kg body weight], was found to significantly increase uterine...... or lower potency. Bioavailability, metabolism, the ability to alter ER alpha distribution in the uterus and the estrogenic potential of parent compound and metabolites may thus contribute to the differences in in vivo estrogenicity of dietary flavonoids....

  12. The differential association of conjugated equine estrogen and esterified estrogen with activated protein C resistance in postmenopausal women

    NARCIS (Netherlands)

    Smith, N. L.; Heckbert, S. R.; Doggen, C. J.; Lemaitre, R. N.; Reiner, A. P.; Lumley, T.; Meijers, J. C. M.; Psaty, B. M.; Rosendaal, F. R.

    2006-01-01

    OBJECTIVES: Clinical trials have demonstrated that oral conjugated equine estrogen (CEE) therapy with or without medroxyprogesterone (MPA) increases venous thrombotic risk but this safety issue has not been investigated for other oral estrogens. Based on observational study findings that esterified

  13. Computational method for discovery of estrogen responsive genes

    DEFF Research Database (Denmark)

    Tang, Suisheng; Tan, Sin Lam; Ramadoss, Suresh Kumar

    2004-01-01

    Estrogen has a profound impact on human physiology and affects numerous genes. The classical estrogen reaction is mediated by its receptors (ERs), which bind to the estrogen response elements (EREs) in target gene's promoter region. Due to tedious and expensive experiments, a limited number of hu...

  14. Estrogenic effects of fusarielins in human breast cancer cell lines

    DEFF Research Database (Denmark)

    Søndergaard, Teis; Klitgaard, Louise Graabæk; Purup, Stig

    2012-01-01

    without the estrogen receptor-α and MCF-10a cells without estrogen receptors were not stimulated by fusarielins. Furthermore, the stimulation was prevented in MCF-7 cells when fusarielins were incubated in the presence of the estrogen receptor antagonist fulvestrant. These observations suggest...

  15. The immunologic effects of estrogen on psoriasis: A comprehensive review

    Directory of Open Access Journals (Sweden)

    Melissa Danesh, B.S.

    2015-06-01

    Conclusions: Increased estrogen production in pregnancy is associated with decreased Th1 and Th17 cytokine production. While estrogen may be responsible for some of these immune shifts resulting in disease improvement, there remains no definitive evidence to prove the hypothesis that estrogen is responsible for such improvement.

  16. Molecular analysis of human endometrium: Short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling

    NARCIS (Netherlands)

    P. Hanifi-Moghaddam (Payman); B. Boers-Sijmons (Bianca); A.H.A. Klaassens (Anet); F.H. van Wijk (Heidy); M.A. den Bakker (Michael); M.C. Ott; G.L. Shipley; H.A.M. Verheul (Herman); H.J. Kloosterboer (Helenius); C.W. Burger (Curt); L.J. Blok (Leen)

    2007-01-01

    textabstractTibolone, a tissue-selective compound with a combination of estrogenic, progestagenic, and androgenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. The current

  17. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    Science.gov (United States)

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Estrogen and early-onset Alzheimer's disease

    NARCIS (Netherlands)

    A.J.C. Slooter (Arjen); J.B. Bronzova (Juliana); A. Hofman (Albert); C. van Broeckhoven (Christine); C.M. van Duijn (Cornelia); J.C.M. Witteman (Jacqueline)

    1999-01-01

    textabstractEstrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5 years) and place of

  19. Expression of Estrogen and Progesterone Receptors among ...

    African Journals Online (AJOL)

    Study design: This is a descriptive study to detect the level of Estrogen (ER) and Progesterone (PR) receptors in a sample of biopsies from Sudanese women with breast cancer presented at Khartoum teaching Hospital Material and Methods: Forty biopsies from breast cancer patients were examined with immunostaining

  20. Xeno-estrogenic compounds in precipitation

    NARCIS (Netherlands)

    Peters, R.J.B.; Beeltje, H.; Delft, R.J. van

    2008-01-01

    The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The

  1. Urinary estrogen metabolites and breast cancer

    DEFF Research Database (Denmark)

    Dallal, Cher M; Stone, Roslyn A; Cauley, Jane A

    2013-01-01

    Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16a-hydroxyestrone (16a-OHE1......), and their ratio (2:16a-OHE1) in relation to breast cancer risk. ¿Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using...... premenopausal 2:16a-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16a-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvs...

  2. Characterizing the Estrogenic Potential of 1060 Environmental ...

    Science.gov (United States)

    In order to detect environmental chemicals that pose a risk of endocrine disruption, high-throughput screening (HTS) tests capable of testing thousands of environmental chemicals are needed. Alteration of estrogen signaling has been implicated in a variety of adverse health effects including cancer promotion, reproductive deficits, and vascular effects. Here we investigate the estrogenic potential of 1060 chemicals of environmental relevance using a real-time measure of growth kinetics by electrode impedance in the estrogen-responsive human ductal carcinoma, T47D cell line. Cells were treated in concentration response and measurements of cellular impedance were recorded every hour for six days. Progestens, androgens, and mineralocortocoids (progesterone, dihydrotestosterone, aldosterone) invoked a biphasic impedance signature that contrasted with the anticipated exponential impedance observed in response to known estrogen receptor agonists (17β-estradiol, genestein, bisphenol-A, nonylphenol, 4-tert-octylphenol). Several compounds, including bisphenol-A, and genestein caused impedance comparable to that of 17β-estradiol, although at much higher concentrations. Additionally, trenbolone and cyproterone acetate invoked the characteristic biphasic signature observed with other endogenous steroid hormones. The continuous real-time nature of this assay allows for the rapid detection of differential growth characteristics not easily detected by traditional cell prol

  3. Estrogen Levels in the three Trimesters

    African Journals Online (AJOL)

    estrogen levels in first, second and third trimesters of pregnant albino rats. MATERIALS AND METHODS. TEST SUBJECTS. 20 female albino rats and 6 male albino rats, with initial weight of 165-180g were purchase from the animal house of Department of Animal and. Environmental Biology , University of Benin,. Benin city ...

  4. [Equine estrogens vs. esterified estrogens in the climacteric and menopause. The controversy arrives in Mexico].

    Science.gov (United States)

    Velasco-Murillo, V

    2001-01-01

    It exists controversies about if the effects and benefits of the esterified estrogens could be similar to those informed for equines, because its chemical composition and bioavailability are different. Esterified estrogens has not delta 8,9 dehydroestrone, and its absorption and level of maximum plasmatic concentrations are reached very fast. In United States of America and another countries, esterified estrogens has been marketed and using for treatment of climacteric syndrome and prevention of postmenopausal osteoporosis, based on the pharmacopoiea of that country, but the Food and Drug administration (FDA) has not yet authorized up today, a generic version of conjugated estrogens. In Instituto Mexicano del Seguro Social (IMSS) and another institutions of health sector in Mexico, starting in year 2000, it has been used esterified estrogens for medical treatment of climacteric and menopausal conditions. For this reason, in this paper we revised the most recent information about pharmacology, chemical composition, clinical use and costs of the conjugated estrogens with the purpose to guide the decisions to purchase this kind of drugs in Mexican heath institutions.

  5. Estrogen promotes megakaryocyte polyploidization via estrogen receptor beta-mediated transcription of GATA1.

    Science.gov (United States)

    Du, C; Xu, Y; Yang, K; Chen, S; Wang, X; Wang, S; Wang, C; Shen, M; Chen, F; Chen, M; Zeng, D; Li, F; Wang, T; Wang, F; Zhao, J; Ai, G; Cheng, T; Su, Y; Wang, J

    2017-04-01

    Estrogen is reported to be involved in thrombopoiesis and the disruption of its signaling may cause myeloproliferative disease, yet the underlying mechanisms remain largely unknown. GATA-binding factor 1 (GATA1) is a key regulator of megakaryocyte (MK) differentiation and its deficiency will lead to megakaryoblastic leukemia. Here we show that estrogen can dose-dependently promote MK polyploidization and maturation via activation of estrogen receptor beta (ERβ), accompanied by a significant upregulation of GATA1. Chromatin immunoprecipitation and a dual luciferase assay demonstrate that ERβ can directly bind the promoter region of GATA1 and activate its transcription. Steroid receptor coactivator 3 (SRC3) is involved in ERβ-mediated GATA1 transcription. The deficiency of ERβ or SRC3, similar to the inhibition of GATA1, leads to the impediment of estrogen-induced MK polyploidization and platelet production. Further investigations reveal that signal transducer and activator of transcription 1 signaling pathway downstream of GATA1 has a crucial role in estrogen-induced MK polyploidization, and ERβ-mediated GATA1 upregulation subsequently enhances nuclear factor erythroid-derived 2 expression, thereby promoting proplatelet formation and platelet release. Our study provides a deep insight into the molecular mechanisms of estrogen signaling in regulating thrombopoiesis and the pathogenesis of ER deficiency-related leukemia.

  6. Identification of an estrogenic hormone receptor in Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Mimoto, Ai; Fujii, Madoka; Usami, Makoto; Shimamura, Maki; Hirabayashi, Naoko; Kaneko, Takako; Sasagawa, Noboru; Ishiura, Shoichi

    2007-01-01

    Changes in both behavior and gene expression occur in Caenorhabditis elegans following exposure to sex hormones such as estrogen and progesterone, and to bisphenol A (BPA), an estrogenic endocrine-disrupting compound. However, only one steroid hormone receptor has been identified. Of the 284 known nuclear hormone receptors (NHRs) in C. elegans, we selected nhr-14, nhr-69, and nhr-121 for analysis as potential estrogenic hormone receptors, because they share sequence similarity with the human estrogen receptor. First, the genes were cloned and expressed in Escherichia coli, and then the affinity of each protein for estrogen was determined using a surface plasmon resonance (SPR) biosensor. All three NHRs bound estrogen in a dose-dependent fashion. To evaluate the specificity of the binding, we performed a solution competition assay using an SPR biosensor. According to our results, only NHR-14 was able to interact with estrogen. Therefore, we next examined whether nhr-14 regulates estrogen signaling in vivo. To investigate whether these interactions actually control the response of C. elegans to hormones, we investigated the expression of vitellogenin, an estrogen responsive gene, in an nhr-14 mutant. Semi-quantitative RT-PCR showed that vitellogenin expression was significantly reduced in the mutant. This suggests that NHR-14 is a C. elegans estrogenic hormone receptor and that it controls gene expression in response to estrogen

  7. Estrogen and its role in gastrointestinal health and disease.

    LENUS (Irish Health Repository)

    Hogan, Aisling M

    2012-02-01

    INTRODUCTION: While the concept of a role of estrogen in gastrointestinal (in particular, colonic) malignancy has generated excitement in recent years, no review has examined the role of this potent and omnipresent steroid hormone in physiological states or its contribution to the development of benign pathological processes. Understanding these effects (and mechanisms therein) may provide a platform for a deeper understanding of more complex disease processes. METHODS: A literature search was conducted using the PubMed database and the search terms were "estrogen," "estrogen AND gastrointestinal tract," "estrogen AND colon," "estrogen AND esophagus," "estrogen AND small intestine," "estrogen AND stomach," "estrogen AND gallbladder," and "estrogen AND motility." Bibliographies of extracted studies were further cross-referenced. In all, 136 full-text articles were selected for review. A logical organ-based approach was taken to enable extraction of data of clinical relevance and meaningful interpretation thereof. Insight is provided into the hypotheses, theories, controversies, and contradictions generated over the last five decades by extensive investigation of estrogen in human, animal, and cell models using techniques as diverse as autoradiographic studies of baboons to human population analysis. CONCLUSIONS: Effects from esophagus through to the colon and rectum are summarized in this first concise collection of data pertaining to estrogenic actions in gastrointestinal health and disease. Mechanisms of these actions are discussed where possible. Undoubtedly, this hormone exerts many actions yet to be elucidated, and its potential therapeutic applications remain, as yet, largely unexplored.

  8. Estrogens and male reproduction: a new concept

    Directory of Open Access Journals (Sweden)

    S. Carreau

    2007-06-01

    Full Text Available The mammalian testis serves two main functions: production of spermatozoa and synthesis of steroids; among them estrogens are the end products obtained from the irreversible transformation of androgens by a microsomal enzymatic complex named aromatase. The aromatase is encoded by a single gene (cyp19 in humans which contains 18 exons, 9 of them being translated. In rats, the aromatase activity is mainly located in Sertoli cells of immature rats and then in Leydig cells of adult rats. We have demonstrated that germ cells represent an important source of estrogens: the amount of P450arom transcript is 3-fold higher in pachytene spermatocytes compared to gonocytes or round spermatids; conversely, aromatase activity is more intense in haploid cells. Male germ cells of mice, bank voles, bears, and monkeys express aromatase. In humans, we have shown the presence of a biologically active aromatase and of estrogen receptors (alpha and ß in ejaculated spermatozoa and in immature germ cells in addition to Leydig cells. Moreover, we have demonstrated that the amount of P450arom transcripts is 30% lower in immotile than in motile spermatozoa. Alterations of spermatogenesis in terms of number and motility of spermatozoa have been described in men genetically deficient in aromatase. These last observations, together with our data showing a significant decrease of aromatase in immotile spermatozoa, suggest that aromatase could be involved in the acquisition of sperm motility. Thus, taking into account the widespread localization of aromatase and estrogen receptors in testicular cells, it is obvious that, besides gonadotrophins and androgens, estrogens produced locally should be considered to be physiologically relevant hormones involved in the regulation of spermatogenesis and spermiogenesis.

  9. Analysis of estrogenic activity in environmental waters in Rio de Janeiro state (Brazil) using the yeast estrogen screen.

    Science.gov (United States)

    Dias, Amanda Cristina Vieira; Gomes, Frederico Wegenast; Bila, Daniele Maia; Sant'Anna, Geraldo Lippel; Dezotti, Marcia

    2015-10-01

    The estrogenicity of waters collected from an important hydrological system in Brazil (Paraiba do Sul and Guandu Rivers) was assessed using the yeast estrogen screen (YES) assay. Sampling was performed in rivers and at the outlets of conventional water treatment plants (WTP). The removal of estrogenic activity by ozonation and chlorination after conventional water treatment (clarification and sand filtration) was investigated employing samples of the Guandu River spiked with estrogens and bisphenol A (BPA). The results revealed a preoccupying incidence of estrogenic activity at levels higher than 1ngL(-1) along some points of the rivers. Another matter of concern was the number of samples from WTPs presenting estrogenicity surpassing 1ngL(-1). The oxidation techniques (ozonation and chlorination) were effective for the removal of estrogenic activity and the combination of both techniques led to good results using less amounts of oxidants. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Yeast Estrogen Screen Assay as a Tool for Detecting Estrogenic Activity in Water Bodies

    Directory of Open Access Journals (Sweden)

    Mirjana Bistan

    2012-01-01

    Full Text Available The presence of endocrine-disrupting compounds in wastewater, surface water, groundwater and even drinking water has become a major concern worldwide, since they negatively affect wildlife and humans. Therefore, these substances should be effectively removed from effluents before they are discharged into surface water to prevent pollution of groundwater, which can be a source of drinking water. Furthermore, an efficient control of endocrine-disrupting compounds in wastewater based on biological and analytical techniques is required. In this study, a yeast estrogen screen (YES bioassay has been introduced and optimized with the aim to assess potential estrogenic activity of waters. First, assay duration, concentration of added substrate to the assay medium and wavelength used to measure the absorbance of the substrate were estimated. Several compounds, such as 17-β-estradiol, 17-α-ethinylestradiol, bisphenol A, nonylphenol, genisteine, hydrocortisone, dieldrin, atrazine, methoxychlor, testosterone and progesterone were used to verify its specificity and sensitivity. The optimized YES assay was sensitive and responded specifically to the selected estrogenic and nonestrogenic compounds in aqueous samples. Potential estrogenicity of influent and effluent samples of two wastewater treatment plants was assessed after the samples had been concentrated by solid-phase extraction (SPE procedure using Oasis® HLB cartridges and methanol as eluting solvent. Up to 90 % of relative estrogenic activity was detected in concentrated samples of influents to wastewater treatment plants and estrogenic activity was still present in the concentrated effluent samples. We found that the introduced YES assay is a suitable screening tool for monitoring the potential estrogenicity of effluents that are discharged into surface water.

  11. Estrogen regulates estrogen receptors and antioxidant gene expression in mouse skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Kristen A Baltgalvis

    Full Text Available BACKGROUND: Estrogens are associated with the loss of skeletal muscle strength in women with age. Ovarian hormone removal by ovariectomy in mice leads to a loss of muscle strength, which is reversed with 17beta-estradiol replacement. Aging is also associated with an increase in antioxidant stress, and estrogens can improve antioxidant status via their interaction with estrogen receptors (ER to regulate antioxidant gene expression. The purpose of this study was to determine if ER and antioxidant gene expression in skeletal muscle are responsive to changes in circulating estradiol, and if ERs regulate antioxidant gene expression in this tissue. METHODOLOGY/PRINCIPAL FINDINGS: Adult C57BL/6 mice underwent ovariectomies or sham surgeries to remove circulating estrogens. These mice were implanted with placebo or 17beta-estradiol pellets acutely or chronically. A separate experiment examined mice that received weekly injections of Faslodex to chronically block ERs. Skeletal muscles were analyzed for expression of ER genes and proteins and antioxidant genes. ERalpha was the most abundant, followed by Gper and ERbeta in both soleus and EDL muscles. The loss of estrogens through ovariectomy induced ERalpha gene and protein expression in the soleus, EDL, and TA muscles at both the acute and chronic time points. Gpx3 mRNA was also induced both acutely and chronically in all 3 muscles in mice receiving 17beta-estradiol. When ERs were blocked using Faslodex, Gpx3 mRNA was downregulated in the soleus muscle, but not the EDL and TA muscles. CONCLUSIONS/SIGNIFICANCE: These data suggest that Gpx3 and ERalpha gene expression are sensitive to circulating estrogens in skeletal muscle. ERs may regulate Gpx3 gene expression in the soleus muscle, but skeletal muscle regulation of Gpx3 via ERs is dependent upon muscle type. Further work is needed to determine the indirect effects of estrogen and ERalpha on Gpx3 expression in skeletal muscle, and their importance in the

  12. Estrogen replacement therapy and cardioprotection: mechanisms and controversies

    Directory of Open Access Journals (Sweden)

    M.T.R. Subbiah

    2002-03-01

    Full Text Available Epidemiological and case-controlled studies suggest that estrogen replacement therapy might be beneficial in terms of primary prevention of coronary heart disease (CHD. This beneficial effect of estrogens was initially considered to be due to the reduction of low density lipoproteins (LDL and to increases in high density lipoproteins (HDL. Recent studies have shown that estrogens protect against oxidative stress and decrease LDL oxidation. Estrogens have direct effects on the arterial tissue and modulate vascular reactivity through nitric oxide and prostaglandin synthesis. While many of the effects of estrogen on vascular tissue are believed to be mediated by estrogen receptors alpha and ß, there is evidence for `immediate non-genomic' effects. The role of HDL in interacting with 17ß-estradiol including its esterification and transfer of esterified estrogens to LDL is beginning to be elucidated. Despite the suggested positive effects of estrogens, two recent placebo-controlled clinical trials in women with CHD did not detect any beneficial effects on overall coronary events with estrogen therapy. In fact, there was an increase in CHD events in some women. Mutations in thrombogenic genes (factor V Leiden, prothrombin mutation, etc. in a subset of women may play a role in this unexpected finding. Thus, the cardioprotective effect of estrogens appears to be more complicated than originally thought and requires more research.

  13. Estrogen therapy: the dangerous road to Shangri-La.

    Science.gov (United States)

    1976-11-01

    The use of estrogens almost tripled during the 1965-75 period, with usage concentrated as a cure-all for aging, for the degenerative diseases associated with aging, and for the emotional difficulties of middle age. 3 separate studies published in the last year have shown a high level of association between estrogen use and the development of endometrial cancer. Results of these studies coupled with the significant recent increase in the incidence of cancer in women over 50 who are in the high socioeconomic groups--the groups most likely to use estrogen therapy--emphasize the association. The U.S. FDA has proposed a modification in the labeling for estrogens, and a package insert for patients which would warn of possible hazards of estrogen therapy. It is recommended that estrogen be used only for vasomotor symptoms and vaginal atrophy. The lowest possible effective dosage should be used and for the shortest possible amount of time. Earlier studies had suggested that estrogen replacement therapy might protect against breast cancer; most recent studies suggest the opposite. In addition, estrogen may trigger high blood pressure and increase some blood clotting. Women with high blood pressure or a family history of early heart attacks are contraindicated from using estrogen therapy. Even for the treatment of osteoporosis, there may be safer alternative therapies. Women are cautioned as to their own responsibilities when taking estrogens.

  14. Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer.

    Science.gov (United States)

    Mishra, Sweta; Tai, Qin; Gu, Xiang; Schmitz, James; Poullard, Ashley; Fajardo, Roberto J; Mahalingam, Devalingam; Chen, Xiaodong; Zhu, Xueqiong; Sun, Lu-Zhe

    2015-12-29

    The role of estrogen signaling in regulating prostate tumorigenesis is relatively underexplored. Although, an increasing body of evidence has linked estrogen receptor beta (ERß) to prostate cancer, the function of estrogen receptor alpha (ERα) in prostate cancer is not very well studied. We have discovered a novel role of ERα in the pathogenesis of prostate tumors. Here, we show that prostate cancer cells express ERα and estrogen induces oncogenic properties in prostate cancer cells through ERα. Importantly, ERα knockdown in the human prostate cancer PacMetUT1 cells as well as pharmacological inhibition of ERα with ICI 182,780 inhibited osteoblastic lesion formation and lung metastasis in vivo. Co-culture of pre-osteoblasts with cancer cells showed a significant induction of osteogenic markers in the pre-osteoblasts, which was attenuated by knockdown of ERα in cancer cells suggesting that estrogen/ERα signaling promotes crosstalk between cancer and osteoblastic progenitors to stimulate osteoblastic tumorigenesis. These results suggest that ERα expression in prostate cancer cells is essential for osteoblastic lesion formation and lung metastasis. Thus, inhibition of ERα signaling in prostate cancer cells may be a novel therapeutic strategy to inhibit the osteoblastic lesion development as well as lung metastasis in patients with advanced prostate cancer.

  15. Quality control of estrogen receptor assays.

    Science.gov (United States)

    Godolphin, W; Jacobson, B

    1980-01-01

    Four types of material have been used for the quality control of routine assays of estrogen receptors in human breast tumors. Pieces of hormone-dependent Nb rat mammary tumors gave a precision about 40%. Rat uteri and rat tumors pulverized at liquid nitrogen temperature and stored as powder yielded precision about 30%. Powdered and lyophilised human tumors appear the best with precision as good as 17%.

  16. Estrogen sulfotransferases in breast and endometrial cancers.

    Science.gov (United States)

    Pasqualini, Jorge Raul

    2009-02-01

    Estrogen sulfotransferase is significantly more active in the normal breast cell (e.g., Human 7) than in the cancer cell (e.g., MCF-7). The data suggest that in breast cancer sulfoconjugated activity is carried out by another enzyme, the SULT1A, which acts at high concentration of the substrates. In breast cancer cells sulfotransferase (SULT) activity can be stimulated by various progestins: medrogestone, promegestone, and nomegestrol acetate, as well as by tibolone and its metabolites. SULT activities can also be controlled by other substances including phytoestrogens, celecoxib, flavonoids (e.g., quercetin, resveratrol), and isoflavones. SULT expression was localized in breast cancer cells, which can be stimulated by promegestone and correlated with the increase of the enzyme activity. The estrogen sulfotransferase (SULT1E1), which acts at nanomolar concentration of estradiol, can inactivate most of this hormone present in the normal breast; however, in the breast cancer cells, the sulfotransferase denoted as SULT1A1 is mainly present, and this acts at micromolar concentrations of E(2). A correlation was postulated among breast cancer cell proliferation, the effect of various progestins, and sulfotransferase stimulation. In conclusion, it is suggested that factors involved in the stimulation of the estrogen sulfotransferases could provide new possibilities for the treatment of patients with hormone-dependent breast and endometrial cancers.

  17. Estrogen, Progesterone and Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Ho Shuk-Mei

    2003-10-01

    Full Text Available Abstract Ovarian carcinoma (OCa continues to be the leading cause of death due to gynecologic malignancies and the vast majority of OCa is derived from the ovarian surface epithelium (OSE and its cystic derivatives. Epidemiological evidence strongly suggests that steroid hormones, primarily estrogens and progesterone, are implicated in ovarian carcinogenesis. However, it has proved difficult to fully understand their mechanisms of action on the tumorigenic process. New convincing data have indicated that estrogens favor neoplastic transformation of the OSE while progesterone offers protection against OCa development. Specifically, estrogens, particularly those present in ovulatory follicles, are both genotoxic and mitogenic to OSE cells. In contrast, pregnancy-equivalent levels progesterone are highly effective as apoptosis inducers for OSE and OCa cells. In this regard, high-dose progestin may exert an exfoliation effect and rid an aged OSE of pre-malignant cells. A limited number of clinical studies has demonstrated efficacies of antiestrogens, aromatase inhibitors, and progestins alone or in combination with chemotherapeutic drugs in the treatment of OCa. As a result of increased life expectancy in most countries, the number of women taking hormone replacement therapies (HRT continues to grow. Thus, knowledge of the mechanism of action of steroid hormones on the OSE and OCa is of paramount significance to HRT risk assessment and to the development of novel therapies for the prevention and treatment of OCa.

  18. Estrogen inhibits Dlk1/FA1 production: A potential mechanism for estrogen effects on bone turnover

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Bay-Jensen, Anne-Christine; Srinivasan, Bhuma

    2011-01-01

    We have recently identified delta-like 1/fetal antigen 1 (Dlk1/FA1) as a novel regulator of bone mass that functions to mediate bone loss under estrogen deficiency in mice. In this report, we investigated the effects of estrogen (E) deficiency and E replacement on serum (s) levels of Dlk1/FA1 (s......-Dlk1FA1) and its correlation with bone turnover markers. s-Dlk1/FA1 and bone turnover markers (serum cross-linked C-telopeptide [s-CTX] and serum osteocalcin) were measured in two cohorts: a group of pre- and postmenopausal women (n = 100) and a group of postmenopausal women, where half had received...... estrogen-replacement therapy (ERT, n = 166). s-Dlk1/FA1 and s-CTX were elevated in postmenopausal E-deficient women compared with premenopausal E-replete women (both p ...

  19. Estrogens and Androgens in Skeletal Physiology and Pathophysiology

    OpenAIRE

    Almeida, Maria; Laurent, Michaël R.; Dubois, Vanessa; Claessens, Frank; O'Brien, Charles A.; Bouillon, Roger; Vanderschueren, Dirk; Manolagas, Stavros C.

    2016-01-01

    Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably t...

  20. Association of Increased Prenatal Estrogen With Risk Factors for Schizophrenia

    OpenAIRE

    Brown, James S.

    2010-01-01

    The author previously described a theoretical cause of schizophrenia based on the effects of estrogenic endocrine disruption. In the current review, the author describes how increased estrogen during pregnancy increases susceptibility to certain viral infections associated with increased risk for schizophrenia. The review further discusses how prenatal estrogen exposure could explain associations of schizophrenia with autoimmune diseases, urban environments, and stress. Based on the associati...

  1. A recombinant estrogen receptor fragment-based homogeneous fluorescent assay for rapid detection of estrogens.

    Science.gov (United States)

    Wang, Dan; Xie, Jiangbi; Zhu, Xiaocui; Li, Jinqiu; Zhao, Dongqin; Zhao, Meiping

    2014-05-15

    In this work, we demonstrate a novel estrogenic receptor fragment-based homogeneous fluorescent assay which enables rapid and sensitive detection of 17β-estradiol (E2) and other highly potent estrogens. A modified human estrogenic receptor fragment (N-His × 6-hER270-595-C-Strep tag II) has been constructed that contains amino acids 270-595 of wild-type human estrogenic receptor α (hER270-595) and two specific tags (6 × His and Strep tag II) fused to the N and C terminus, respectively. The designed receptor protein fragment could be easily produced by prokaryotic expression with high yield and high purity. The obtained protein exhibits high binding affinity to E2 and the two tags greatly facilitate the application of the recombinant protein. Taking advantage of the unique spectroscopic properties of coumestrol (CS), a fluorescent phytoestrogen, a CS/hER270-595-based fluorescent assay has been developed which can sensitively respond to E2 within 1.0 min with a linear working range from 0.1 to 20 ng/mL and a limit of detection of 0.1 ng/mL. The assay was successfully applied for rapid detection of E2 in the culture medium of rat hippocampal neurons. The method also holds great potential for high-throughput monitoring the variation of estrogen levels in complex biological fluids, which is crucial for investigation of the molecular basis of various estrogen-involved processes. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens

    International Nuclear Information System (INIS)

    Shyu, Conrad; Cavileer, Timothy D.; Nagler, James J.; Ytreberg, F. Marty

    2011-01-01

    Environmental estrogens have been the subject of intense research due to their documented detrimental effects on the health of fish and wildlife and their potential to negatively impact humans. A complete understanding of how these compounds affect health is complicated because environmental estrogens are a structurally heterogeneous group of compounds. In this work, computational molecular dynamics simulations were utilized to predict the binding affinity of different compounds using rainbow trout (Oncorhynchus mykiss) estrogen receptors (ERs) as a model. Specifically, this study presents a comparison of the binding affinity of the natural ligand estradiol-17β to the four rainbow trout ER isoforms with that of three known environmental estrogens 17α-ethinylestradiol, bisphenol A, and raloxifene. Two additional compounds, atrazine and testosterone, that are known to be very weak or non-binders to ERs were tested. The binding affinity of these compounds to the human ERα subtype is also included for comparison. The results of this study suggest that, when compared to estradiol-17β, bisphenol A binds less strongly to all four receptors, 17α-ethinylestradiol binds more strongly, and raloxifene has a high affinity for the α subtype only. The results also show that atrazine and testosterone are weak or non-binders to the ERs. All of the results are in excellent qualitative agreement with the known in vivo estrogenicity of these compounds in the rainbow trout and other fishes. Computational estimation of binding affinities could be a valuable tool for predicting the impact of environmental estrogens in fish and other animals.

  3. Estrogen receptor mRNA in mineralized tissues of rainbow trout: calcium mobilization by estrogen.

    Science.gov (United States)

    Armour, K J; Lehane, D B; Pakdel, F; Valotaire, Y; Graham, R; Russell, R G; Henderson, I W

    1997-07-07

    RT-PCR was undertaken on total RNA extracts from bone and scales of the rainbow trout, Oncorhynchus mykiss. The rainbow trout estrogen receptor (ER)-specific primers used amplified a single product of expected size from each tissue which, using Southern blotting, strongly hybridized with a 32P-labelled rtER probe under stringent conditions. These data provide the first in vivo evidence of ER mRNA in bone and scale tissues of rainbow trout and suggest that the effects of estrogen observed in this study (increased bone mineral and decreased scale mineral contents, respectively) may be mediated directly through ER.

  4. Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Caroline [Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5056 (United States); Grimaldi, Marina; Boulahtouf, Abdelhay [Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé de la Recherche Médicale U896, Institut Régional de Cancérologie de Montpellier, Université Montpellier 1, 34298 Montpellier (France); Pakdel, Farzad [Institut de Recherche sur la Santé, Environnement et Travail (IRSET), INSERM U1085, Université de Rennes 1, Rennes (France); Brion, François; Aït-Aïssa, Sélim [Unité Écotoxicologie In Vitro et In Vivo, INERIS, Parc ALATA, 60550 Verneuil-en-Halatte (France); Cavaillès, Vincent [Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé de la Recherche Médicale U896, Institut Régional de Cancérologie de Montpellier, Université Montpellier 1, 34298 Montpellier (France); Bourguet, William [U1054, Centre de Biochimie Structurale, CNRS UMR5048, Université Montpellier 1 et 2, 34290 Montpellier (France); Gustafsson, Jan-Ake [Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5056 (United States); Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge (Sweden); and others

    2014-10-01

    Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28 °C as compared to 37 °C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology. - Highlights: • Zebrafish is increasingly used to study the effects of estrogens. • We assessed the activity of pharmaceutical and environmental estrogens on zfERs. • Environmental estrogens displayed greater potency for zfERα compared to zfERβs. • hERβ selective agonists displayed greater potency for zf

  5. Estrogens and Androgens in Skeletal Physiology and Pathophysiology.

    Science.gov (United States)

    Almeida, Maria; Laurent, Michaël R; Dubois, Vanessa; Claessens, Frank; O'Brien, Charles A; Bouillon, Roger; Vanderschueren, Dirk; Manolagas, Stavros C

    2017-01-01

    Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution. Copyright © 2017 the American Physiological Society.

  6. Estrogen-related and other disease diagnoses preceding Parkinson's disease

    DEFF Research Database (Denmark)

    Latourelle, Jeanne C; Dybdal, Merete; Destefano, Anita L

    2010-01-01

    Estrogen exposure has been associated with the occurrence of Parkinson's disease (PD), as well as many other disorders, and yet the mechanisms underlying these relations are often unknown. While it is likely that estrogen exposure modifies the risk of various diseases through many different...... mechanisms, some estrogen-related disease processes might work in similar manners and result in association between the diseases. Indeed, the association between diseases need not be due only to estrogen-related factors, but due to similar disease processes from a variety of mechanisms....

  7. Estrogen signaling in the proliferative endometrium: implications in endometriosis

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Pereira da Costa e Silva

    2016-02-01

    Full Text Available SUMMARY Even though the physiological role of estrogen in the female reproductive cycle and endometrial proliferative phase is well established, the signaling pathways by which estrogen exerts its action in the endometrial tissue are still little known. In this regard, advancements in cell culture techniques and maintenance of endometrial cells in cultures enabled the discovery of new signaling mechanisms activated by estrogen in the normal endometrium and in endometriosis. This review aims to present the recent findings in the genomic and non-genomic estrogen signaling pathways in the proliferative human endometrium specifically associated with the pathogenesis and development of endometriosis.

  8. Vitellogenin, a Marker of Estrogen Mimicking Contaminants in Fishes: Characterization, Quantification and Interference by Anti-Estrogens

    OpenAIRE

    Palumbo, Amanda J.

    2008-01-01

    Vitellogenin (Vg), the estrogen inducible protein precursor to egg yolk, serves as an indicator of exposure to estrogen mimicking environmental contaminants. Vg was isolated by size exclusion and ion exchange chromatography from plasma of California halibut (Paralichthys californicus) treated with estrogen. MALDI TOF mass spectrometry (MS) analysis resulted in a molecular mass of 188 kDa. MS/MS de novo sequencing provided evidence that California halibut has more than one form of Vg. Similar ...

  9. Estrogens and cognition: Friends or foes?: An evaluation of the opposing effects of estrogens on learning and memory.

    Science.gov (United States)

    Korol, Donna L; Pisani, Samantha L

    2015-08-01

    This article is part of a Special Issue "Estradiol and cognition". Estrogens are becoming well known for their robust enhancement on cognition particularly for learning and memory that relies upon functioning of the hippocampus and related neural systems. What is also emerging is that estrogen modulation of cognition is not uniform, at times enhancing yet at other times impairing learning. This review explores the bidirectional effects of estrogens on learning from a multiple memory systems view, focusing on the hippocampus and striatum, whereby modulation by estrogens sorts according to task attributes and neural systems engaged during cognition. We highlight our findings showing that the ability to solve hippocampus-sensitive tasks typically improves under relatively high estrogen status while the ability to solve striatum-sensitive tasks degrades with estrogen exposures. Though constrained by dose and timing of exposure, these opposing enhancements and impairments of cognition can be observed following treatments with different estrogenic compounds including the hormone estradiol, the isoflavone genistein found in soybeans, and agonists that are selective for specific estrogen receptors, suggesting that activation of a single receptor type is sufficient to produce the observed shifts in learning strategies. Using this multi-dimensional framework will allow us to extend our thinking of the relationship between estrogens and cognition to other brain regions and cognitive functions. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Interactions Between the Cytomegalovirus Promoter and the Estrogen Response Element: Implications for Design of Estrogen-Responsive Reporter Plasmids

    OpenAIRE

    Derecka, K.; Wang, C.K.; Flint, A.P.F.

    2006-01-01

    We aimed to produce an estrogen-responsive reporter plasmid that would permit monitoring of estrogen receptor function in the uterus in vivo. The plasmid pBL-tk-CAT(+)ERE was induced by estrogen in bovine endometrial stromal cells. When the CAT gene was replaced by the secreted alkaline phosphatase SeAP, the resulting construct pBL-tk-SeAP(+)ERE remained estrogen responsive. However when the tk promoter was replaced by the cytomegalovirus (cmv) promoter, the resulting plasmid (pBL-cmv-SeAP(+)...

  11. Sex Hormones and Cardiometabolic Health: Role of Estrogen and Estrogen Receptors.

    Science.gov (United States)

    Clegg, Deborah; Hevener, Andrea L; Moreau, Kerrie L; Morselli, Eugenia; Criollo, Alfredo; Van Pelt, Rachael E; Vieira-Potter, Victoria J

    2017-05-01

    With increased life expectancy, women will spend over three decades of life postmenopause. The menopausal transition increases susceptibility to metabolic diseases such as obesity, diabetes, cardiovascular disease, and cancer. Thus, it is more important than ever to develop effective hormonal treatment strategies to protect aging women. Understanding the role of estrogens, and their biological actions mediated by estrogen receptors (ERs), in the regulation of cardiometabolic health is of paramount importance to discover novel targeted therapeutics. In this brief review, we provide a detailed overview of the literature, from basic science findings to human clinical trial evidence, supporting a protective role of estrogens and their receptors, specifically ERα, in maintenance of cardiometabolic health. In so doing, we provide a concise mechanistic discussion of some of the major tissue-specific roles of estrogens signaling through ERα. Taken together, evidence suggests that targeted, perhaps receptor-specific, hormonal therapies can and should be used to optimize the health of women as they transition through menopause, while reducing the undesired complications that have limited the efficacy and use of traditional hormone replacement interventions. Copyright © 2017 Endocrine Society.

  12. Role of estrogen in lung cancer based on the estrogen receptor-epithelial mesenchymal transduction signaling pathways

    Directory of Open Access Journals (Sweden)

    Zhao XZ

    2015-10-01

    Full Text Available Xiao-zhen Zhao,1,* Yu Liu,1,* Li-juan Zhou,1,* Zhong-qi Wang,1 Zhong-hua Wu,2 Xiao-yuan Yang31Department of Tumor, Longhua Hospital, 2Center of Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA*These authors contributed equally to this workBackground/aim: Estrogen is reported to promote the occurrence and development of several human cancers. Increasing evidence shows that most human lung tumors exert estrogen receptor expression. In the present study, we investigated the underlying mechanism of estrogen effect in lung cancer through estrogen receptor-epithelial–mesechymal-transition signaling pathways for the first time.Materials and methods: A total of 36 inbred C57BL/6 mice (18 male and 18 female were injected subcutaneously with human lung adenocarcinoma cell line, Lewis. After the lung tumor model was established, mice with lung adenocarcinoma were randomly divided into three groups for each sex (n=6, such as vehicle group, estrogen group, and estrogen plus tamoxifen group. The six groups of mice were sacrificed after 21 days of drug treatment. Tumor tissue was stripped and weighed, and tumor inhibition rate was calculated based on average tumor weight. Protein and messenger RNA (mRNA expressions of estrogen receptor α (ERα, estrogen receptor β (ERβ, phosphatidylinositol 3'-kinase (PI3K, AKT, E-cadherin, and vimentin were detected in both tumor tissue and lung tissue by using immunohistochemistry and real-time reverse transcription-polymerase chain reaction.Results: 1 For male mice: in the estrogen group, estrogen treatment significantly increased ERα protein and mRNA expressions in tumor tissue and protein expression of PI3K, AKT, and vimentin in both tumor tissue and lung tissue compared with the vehicle-treated group. Besides, m

  13. The anticancer estrogen receptor antagonist tamoxifen impairs consolidation of inhibitory avoidance memory through estrogen receptor alpha.

    Science.gov (United States)

    Lichtenfels, Martina; Dornelles, Arethuza da Silva; Petry, Fernanda Dos Santos; Blank, Martina; de Farias, Caroline Brunetto; Roesler, Rafael; Schwartsmann, Gilberto

    2017-11-01

    Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats. In the first experiment, Wistar female rats received a single oral dose of tamoxifen (1, 3, or 10 mg/kg) or saline by gavage immediately after training and were tested for memory consolidation 24 h after training. In the second experiment, rats received a single dose of 1 mg/kg tamoxifen or saline by gavage 3 h after training and were tested 24 h after training for memory consolidation. In the third experiment, rats received a subcutaneous injection with estrogen receptor α agonist or estrogen receptor beta agonist 30 min before the training. After training, rats received a single oral dose of tamoxifen 1 mg/kg or saline and were tested 24 h after training. In the fourth experiment, rats were trained and tested 24 h later. Immediately after test, rats received a single dose of tamoxifen (1 mg/kg) or saline by gavage and were given four additional daily test trials followed by a re-instatement. Tamoxifen at 1 mg/kg impaired memory consolidation when given immediately after training and the estrogen receptor alpha agonist improved the tamoxifen-related memory impairment. Moreover, tamoxifen impairs memory consolidation of the test. These findings indicate that estrogen receptors regulate the early phase of memory consolidation and the effects of tamoxifen on memory consolidation.

  14. Estrogen is essential but not sufficient to induce endometriosis

    Indian Academy of Sciences (India)

    Mosami Galvankar

    2017-05-11

    May 11, 2017 ... Beyond estrogen, the levels of Estrogen Receptors (ER) are also altered in the ..... lesions were found on the bladder on day 7 and the lesions ..... effects of adipose tissue on cancer development and progression. Endocr. Rev ...

  15. Ozonation of estrogenic chemicals in biologically treated sewage

    DEFF Research Database (Denmark)

    Hansen, Kamilla Marie Speht; Andersen, Henrik Rasmus; Ledin, Anna

    2010-01-01

    The present study shows that ozonation of effluents from municipal wastewater treatment plants (WWTPs) is likely to be a future treatment solution to remove estrogens and xeno-estrogens. The required ozone dose and electrical energy for producing the ozone were determined in two WWTP effluents fo...

  16. Estrogen replacement therapy, Alzheimer's disease, and mild cognitive impairment.

    Science.gov (United States)

    Mulnard, Ruth A; Corrada, Marìa M; Kawas, Claudia H

    2004-09-01

    This article highlights the latest findings regarding estrogen replacement therapy in the treatment and prevention of Alzheimer's disease (AD) and mild cognitive impairment in women. Despite considerable evidence from observational studies, recent randomized clinical trials of conjugated equine estrogens, alone and in combination with progestin, have shown no benefit for either the treatment of established AD or for the short-term prevention of AD, mild cognitive impairment, or cognitive decline. Based on the evidence, there is no role at present for estrogen replacement therapy in the treatment or prevention of AD or cognitive decline, despite intriguing results from the laboratory and from observational studies. However, numerous questions remain about the biologic effects of estrogens on brain structure and function. Additional basic and clinical investigations are necessary to examine different forms and dosages of estrogens, other populations, and the relevance of timing and duration of exposure.

  17. Estrogen, Angiogenesis, Immunity and Cell Metabolism: Solving the Puzzle.

    Science.gov (United States)

    Trenti, Annalisa; Tedesco, Serena; Boscaro, Carlotta; Trevisi, Lucia; Bolego, Chiara; Cignarella, Andrea

    2018-03-15

    Estrogen plays an important role in the regulation of cardiovascular physiology and the immune system by inducing direct effects on multiple cell types including immune and vascular cells. Sex steroid hormones are implicated in cardiovascular protection, including endothelial healing in case of arterial injury and collateral vessel formation in ischemic tissue. Estrogen can exert potent modulation effects at all levels of the innate and adaptive immune systems. Their action is mediated by interaction with classical estrogen receptors (ERs), ERα and ERβ, as well as the more recently identified G-protein coupled receptor 30/G-protein estrogen receptor 1 (GPER1), via both genomic and non-genomic mechanisms. Emerging data from the literature suggest that estrogen deficiency in menopause is associated with an increased potential for an unresolved inflammatory status. In this review, we provide an overview through the puzzle pieces of how 17β-estradiol can influence the cardiovascular and immune systems.

  18. The Critical Role of Estrogen in Menopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    Mrinali Sharma

    2017-12-01

    Full Text Available Osteoporosis is a bone disorder, which causes a reduction in the mass and density of bone tissue, and implants a greater possibility for skeletal fractures to occur. This bone disease is especially relevant for women suffering from menopause. Due to this general prevalence, osteoporosis requires continual intervention in the pharmacological and medicinal industry for better treatment alternatives for patients. A focal point for many scientific research studies for osteoporosis has been estrogen. As a hormone, estrogen exhibits a fluctuating capacity in the woman's body, and this has been proclaimed to be a qualifying explanation as to why women develop osteoporosis after menopause. The purpose of this paper is to interpret estrogen's capacity to treat menopausal osteoporosis. Thus, in this article, estrogen’s significance in bone health and different forms, derivatives, and the combinations of estrogen is examined in terms of efficiency in treating osteoporosis. [J Contemp Med 2017; 7(4.000: 418-427

  19. Long-term use of estrogens: benefit or risk

    Directory of Open Access Journals (Sweden)

    Bogusława Pietrzak

    2015-03-01

    Full Text Available Estrogens are widely used in hormone replacement therapy, gynecology, urogynecology and rarely in dermatology. Non-therapeutic use of estrogens is very widespread. Estrogens are used as contraceptives, which cause a lot of serious side effects. A common clinical problem is skin hyperpigmentation (melasma, occurring mainly in women who take contraceptives with high doses of estrogens. But low doses of estrogens may also cause skin side effects. The mechanism of melasma development is very complicated and not fully understood. It is very likely that UV radiation and genetic background can affect melasma development. Effective therapy should lead to prevention or alleviation of relapses. Treatment should also reduce the area of lesions and improve the appearance of skin. There is no effective and universal pattern of treatment, in which only one substance or method is used. A combination of different methods is used to optimize the therapy. An important role is attributed to prevention, especially protection from UV radiation.

  20. Mechanism of estrogen activation of c-myc oncogene expression.

    Science.gov (United States)

    Dubik, D; Shiu, R P

    1992-08-01

    The estrogen receptor complex is a known trans-acting factor that regulates transcription of specific genes through an interaction with a specific estrogen-responsive cis-acting element (ERE). In previous studies we have shown that in estrogen-responsive human breast cancer cells estrogen rapidly activates c-myc expression. This activated expression occurs through enhanced transcription and does not require the synthesis of new protein intermediates; therefore, an ERE is present in the human c-myc gene regulatory region. To localize the ERE, constructs containing varying lengths of the c-myc 5'-flanking region ranging from -2327 to +25 (relative to the P1 promoter) placed adjacent to the chloramphenicol acetyl transferase reporter gene (CAT) were prepared. They were used in transient transfection studies in MCF-7 and HeLa cells co-transfected with an estrogen receptor expression vector. These studies reveal that all constructs containing the P2 promoter region exhibited estrogen-regulated CAT expression and that a 116-bp region upstream and encompassing the P2 TATA box is necessary for this activity. Analysis of this 116-bp region failed to identify a cis-acting element with sequences resembling the consensus ERE; however, co-transfection studies with mutant estrogen receptor expression vectors showed that the DNA-binding domain of the receptor is essential for estrogen-regulated CAT gene expression. We have also observed that anti-estrogen receptor complexes can weakly trans-activate from this 116-bp region but fail to do so from the ERE-containing ApoVLDLII-CAT construct. To explain these results we propose a new mechanism of estrogen trans-activation in the c-myc gene promoter.

  1. The human oxytocin gene promoter is regulated by estrogens.

    Science.gov (United States)

    Richard, S; Zingg, H H

    1990-04-15

    Gonadal steroids affect brain function primarily by altering the expression of specific genes, yet the specific mechanisms by which neuronal target genes undergo such regulation are unknown. Recent evidence suggests that the expression of the neuropeptide gene for oxytocin (OT) is modulated by estrogens. We therefore examined the possibility that this regulation occurred via a direct interaction of the estrogen-receptor complex with cis-acting elements flanking the OT gene. DNA-mediated gene transfer experiments were performed using Neuro-2a neuroblastoma cells and chimeric plasmids containing portions of the human OT gene 5'-glanking region linked to the chloramphenicol acetyltransferase gene. We identified a 19-base pair region located at -164 to -146 upstream of the transcription start site which is capable of conferring estrogen responsiveness to the homologous as well as to a heterologous promoter. The hormonal response is strictly dependent on the presence of intracellular estrogen receptors, since estrogen induced stimulation occurred only in Neuro-2a cells co-transfected with an expression vector for the human estrogen receptor. The identified region contains a novel imperfect palindrome (GGTGACCTTGACC) with sequence similarity to other estrogen response elements (EREs). To define cis-acting elements that function in synergism with the ERE, sequences 3' to the ERE were deleted, including the CCAAT box, two additional motifs corresponding to the right half of the ERE palindrome (TGACC), as well as a CTGCTAA heptamer similar to the "elegans box" found in Caenorhabditis elegans. Interestingly, optimal function of the identified ERE was fully independent of these elements and only required a short promoter region (-49 to +36). Our studies define a molecular mechanism by which estrogens can directly modulate OT gene expression. However, only a subset of OT neurons are capable of binding estrogens, therefore, direct action of estrogens on the OT gene may be

  2. Interactions between the cytomegalovirus promoter and the estrogen response element: implications for design of estrogen-responsive reporter plasmids.

    Science.gov (United States)

    Derecka, K; Wang, C K; Flint, A P F

    2006-07-01

    We aimed to produce an estrogen-responsive reporter plasmid that would permit monitoring of estrogen receptor function in the uterus in vivo. The plasmid pBL-tk-CAT(+)ERE was induced by estrogen in bovine endometrial stromal cells. When the CAT gene was replaced by the secreted alkaline phosphatase SeAP, the resulting construct pBL-tk-SeAP(+)ERE remained estrogen responsive. However when the tk promoter was replaced by the cytomegalovirus (cmv) promoter, the resulting plasmid (pBL-cmv-SeAP(+)ERE) was not estrogen responsive. Inhibition of ERE function was not due to an effect in trans or due to lack of estrogen receptor. It was not due to an interaction between the cmv promoter and the SeAP gene. cmv promoter function was dependent on NF-kappaB, and mutagenesis in the NF-kappaB sites reduced basal reporter expression without imparting responsiveness to estrogen. A mutation in the TATA box also failed to impart estrogen responsiveness. Modeling of DNA accessibility indicated the ERE was inserted at a site accessible to transcription factors. We conclude that the cmv promoter inhibits ERE function in cis when the two sequences are located in the same construct, and that this effect does not involve an interaction between cmv and reporter gene, NF-kappaB sites or the TATA box, or DNA inaccessibility.

  3. Estrogen biosynthesis in human uterine adenomyosis

    International Nuclear Information System (INIS)

    Urabe, Mamoru; Yamamoto, Takara; Kitawaki, Jo; Honjo, Hideo; Okada, Hiroji

    1989-01-01

    Estrogen biosynthesis (aromatiase activity) was investigated in human adenomyosis tissue and compared with that of the normal myometrium, endometrium, and endometrical cancer tissues. Homogenates were incubated with [1,2,6,7- 3 H]androstenedione and NADPH at 37 deg. C for 1 h. After stopping the enzymatic reaction with ethyl acetate, [4- 14 C]estrone and [4- 14 C]estradiol-17β were added to the incubated sample. Estrone and estradiol were purified and identified by Bio-Rad AG1-X2 column chromatography, thin-layer chromatography and co-crystallization. Estrogen formed in the incubated sample was calculated from the 3 H/ 14 C ratio of the final crystal. The value for estrone formed from androstenedione was 52-132 fmol . h -1. g -1 wet weight. Aromatase activity in the adenomyosis tissues was higher than that in normal endometrial or myometrial tissues, but lower than that found in myometrial or endometrial tumour tissue. Furthermore, we investigated the effect of danazol, progresterone, and medroxyprogesterone acetate on adenomyosis cells in primary cultures. Aromatase activity in adenomyosis was blocked by danazol, but stimulated by progesterone and MPA. These results indicate that aromatase activity in adenomyosis may contribute to the growth of the ectopic endometrial tissue which occurs in this disease. (author)

  4. Peroxidase activity as a marker for estrogenicity

    International Nuclear Information System (INIS)

    Levy, J.; Liel, Y.; Glick, S.M.

    1981-01-01

    We examined the possibility that peroxidase activity might be a marker for estrogen activity in established estrogen-dependent tissues: dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumours and human breast cancer. In DMBA-induced tumours undergoing regression after ovariectomy or tamoxifen treatment, tumour size decreased by 50%, estradiol receptors (ER) and progesterone receptors (PgR) decreased by 25 and 20%, respectively, but peroxidase activity paradoxically increased six- to sevenfold. In DMBA tumours stimulated by estradiol treatment or by the cessation of tamoxifen administration in intact rats, tumour size increased threefold. ER and PgR increased two- and threefold, respectively, while peroxidase activity decreased 50%. These data indicate an inverse relation between tumour growth, ER and PgR on the one hand, and peroxidase activity on the other. In the human breast cancers there was a singificant negative relation between the presence of ER and peroxidase activity. By using a calibrated Sephadex G-100 column it was shown that uterine peroxidase differs in molecular weight from the peroxidase of rat mammary tumours and that of human breast cancer. (author)

  5. Androgens and estrogens in skeletal sexual dimorphism

    Directory of Open Access Journals (Sweden)

    Michaël Laurent

    2014-04-01

    Full Text Available Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T to estradiol (E2 by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refi ned our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen defi ciency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the fi eld of sex steroid actions in male bone homeostasis.

  6. Androgens and estrogens in skeletal sexual dimorphism

    Science.gov (United States)

    Laurent, Michaël; Antonio, Leen; Sinnesael, Mieke; Dubois, Vanessa; Gielen, Evelien; Classens, Frank; Vanderschueren, Dirk

    2014-01-01

    Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T) to estradiol (E2) by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution) peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refined our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen deficiency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the field of sex steroid actions in male bone homeostasis. PMID:24385015

  7. Estrogen-mediated inactivation of FOXO3a by the G protein-coupled estrogen receptor GPER

    International Nuclear Information System (INIS)

    Zekas, Erin; Prossnitz, Eric R.

    2015-01-01

    Estrogen (17β-estradiol) promotes the survival and proliferation of breast cancer cells and its receptors represent important therapeutic targets. The cellular actions of estrogen are mediated by the nuclear estrogen receptors ERα and ERβ as well as the 7-transmembrane spanning G protein-coupled estrogen receptor (GPER). We previously reported that estrogen activates the phosphoinositide 3-kinase (PI3Kinase) pathway via GPER, resulting in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) production within the nucleus of breast cancer cells; however, the mechanisms and consequences of this activity remained unclear. MCF7 breast cancer cells were transfected with GFP-fused Forkhead box O3 (FOXO3) as a reporter to assess localization in response to estrogen stimulation. Inhibitors of PI3Kinases and EGFR were employed to determine the mechanisms of estrogen-mediated FOXO3a inactivation. Receptor knockdown with siRNA and the selective GPER agonist G-1 elucidated the estrogen receptor(s) responsible for estrogen-mediated FOXO3a inactivation. The effects of selective estrogen receptor modulators and downregulators (SERMs and SERDs) on FOXO3a in MCF7 cells were also determined. Cell survival (inhibition of apoptosis) was assessed by caspase activation. In the estrogen-responsive breast cancer cell line MCF7, FOXO3a inactivation occurs on a rapid time scale as a result of GPER, but not ERα, stimulation by estrogen, established by the GPER-selective agonist G-1 and knockdown of GPER and ERα. GPER-mediated inactivation of FOXO3a is effected by the p110α catalytic subunit of PI3Kinase as a result of transactivation of the EGFR. The SERMs tamoxifen and raloxifene, as well as the SERD ICI182,780, were active in mediating FOXO3a inactivation in a GPER-dependent manner. Additionally, estrogen-and G-1-mediated stimulation of MCF7 cells results in a decrease in caspase activation under proapoptotic conditions. Our results suggest that non-genomic signaling by GPER contributes

  8. Activation of estrogen response elements is mediated both via estrogen and muscle contractions in rat skeletal muscle myotubes

    DEFF Research Database (Denmark)

    Wiik, A.; Hellsten, Ylva; Berthelson, P.

    2009-01-01

    is ER independent. The muscle contraction-induced transactivation of ERE and increase in ERbeta mRNA were instead found to be MAP kinase (MAPK) dependent. This study demonstrates for the first time that muscle contractions have a similar functional effect as estrogen in skeletal muscle myotubes, causing......The aim of the present study was to investigate the activation of estrogen response elements (EREs) by estrogen and muscle contractions in rat myotubes in culture and to assess whether the activation is dependent on the estrogen receptors (ERs). In addition, the effect of estrogen and contraction...... on the mRNA levels of ERalpha and ERbeta was studied to determine the functional consequence of the transactivation. Myoblasts were isolated from rat skeletal muscle and transfected with a vector consisting of sequences of EREs coupled to the gene for luciferase. The transfected myoblasts were...

  9. Estrogen inhibits RANKL-stimulated osteoclastic differentiation of human monocytes through estrogen and RANKL-regulated interaction of estrogen receptor-α with BCAR1 and Traf6

    International Nuclear Information System (INIS)

    Robinson, Lisa J.; Yaroslavskiy, Beatrice B.; Griswold, Reed D.; Zadorozny, Eva V.; Guo, Lida; Tourkova, Irina L.; Blair, Harry C.

    2009-01-01

    The effects of estrogen on osteoclast survival and differentiation were studied using CD14-selected mononuclear osteoclast precursors from peripheral blood. Estradiol at ∼ 1 nM reduced RANKL-dependent osteoclast differentiation by 40-50%. Osteoclast differentiation was suppressed 14 days after addition of RANKL even when estradiol was withdrawn after 18 h. In CD14+ cells apoptosis was rare and was not augmented by RANKL or by 17-β-estradiol. Estrogen receptor-α (ERα) expression was strongly down-regulated by RANKL, whether or not estradiol was present. Mature human osteoclasts thus cannot respond to estrogen via ERα. However, ERα was present in CD14+ osteoclast progenitors, and a scaffolding protein, BCAR1, which binds ERα in the presence of estrogen, was abundant. Immunoprecipitation showed rapid (∼ 5 min) estrogen-dependent formation of ERα-BCAR1 complexes, which were increased by RANKL co-treatment. The RANKL-signaling intermediate Traf6, which regulates NF-κB activity, precipitated with this complex. Reduction of NF-κB nuclear localization occurred within 30 min of RANKL stimulation, and estradiol inhibited the phosphorylation of IκB in response to RANKL. Inhibition by estradiol was abolished by siRNA knockdown of BCAR1. We conclude that estrogen directly, but only partially, curtails human osteoclast formation. This effect requires BCAR1 and involves a non-genomic interaction with ERα.

  10. Estrogen inhibits RANKL-stimulated osteoclastic differentiation of human monocytes through estrogen and RANKL-regulated interaction of estrogen receptor-{alpha} with BCAR1 and Traf6

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, Lisa J., E-mail: robinsonlj@msx.upmc.edu [Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Yaroslavskiy, Beatrice B.; Griswold, Reed D.; Zadorozny, Eva V.; Guo, Lida; Tourkova, Irina L. [Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Blair, Harry C. [Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Veteran' s Affairs Medical Center, Pittsburgh, PA 15243 (United States)

    2009-04-15

    The effects of estrogen on osteoclast survival and differentiation were studied using CD14-selected mononuclear osteoclast precursors from peripheral blood. Estradiol at {approx} 1 nM reduced RANKL-dependent osteoclast differentiation by 40-50%. Osteoclast differentiation was suppressed 14 days after addition of RANKL even when estradiol was withdrawn after 18 h. In CD14+ cells apoptosis was rare and was not augmented by RANKL or by 17-{beta}-estradiol. Estrogen receptor-{alpha} (ER{alpha}) expression was strongly down-regulated by RANKL, whether or not estradiol was present. Mature human osteoclasts thus cannot respond to estrogen via ER{alpha}. However, ER{alpha} was present in CD14+ osteoclast progenitors, and a scaffolding protein, BCAR1, which binds ER{alpha} in the presence of estrogen, was abundant. Immunoprecipitation showed rapid ({approx} 5 min) estrogen-dependent formation of ER{alpha}-BCAR1 complexes, which were increased by RANKL co-treatment. The RANKL-signaling intermediate Traf6, which regulates NF-{kappa}B activity, precipitated with this complex. Reduction of NF-{kappa}B nuclear localization occurred within 30 min of RANKL stimulation, and estradiol inhibited the phosphorylation of I{kappa}B in response to RANKL. Inhibition by estradiol was abolished by siRNA knockdown of BCAR1. We conclude that estrogen directly, but only partially, curtails human osteoclast formation. This effect requires BCAR1 and involves a non-genomic interaction with ER{alpha}.

  11. Estrogen in cardiovascular disease during systemic lupus erythematosus.

    Science.gov (United States)

    Gilbert, Emily L; Ryan, Michael J

    2014-12-01

    Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that disproportionately affects women during their childbearing years. Cardiovascular disease is the leading cause of mortality in this patient population at an age when women often have low cardiovascular risk. Hypertension is a major cardiovascular disease risk factor, and its prevalence is markedly increased in women with SLE. Estrogen has traditionally been implicated in SLE disease progression because of the prevalence of the disease in women; however, its role in cardiovascular risk factors such as hypertension is unclear. The objective of this review is to discuss evidence for the role of estrogen in both human and murine SLE with emphasis on the effect of estrogen on cardiovascular risk factors, including hypertension. PubMed was used to search for articles with terms related to estradiol and SLE. The references of retrieved publications were also reviewed. The potential permissive role of estrogen in SLE development is supported by studies from experimental animal models of lupus in which early removal of estrogen or its effects leads to attenuation of SLE disease parameters, including autoantibody production and renal injury. However, data about the role of estrogens in human SLE are much less clear, with most studies not reaching firm conclusions about positive or negative outcomes after hormonal manipulations involving estrogen during SLE (ie, oral contraceptives, hormone therapy). Significant gaps in knowledge remain about the effect of estrogen on cardiovascular risk factors during SLE. Studies in women with SLE were not designed to determine the effect of estrogen or hormone therapy on blood pressure even though hypertension is highly prevalent, and risk of premature ovarian failure could necessitate use of hormone therapy in women with SLE. Recent evidence from an experimental animal model of lupus found that estrogen may protect against cardiovascular risk factors in

  12. Estrogen in Cardiovascular Disease during Systemic Lupus Erythematosus

    Science.gov (United States)

    Gilbert, Emily L.; Ryan, Michael J.

    2015-01-01

    Purpose Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that disproportionately affects women during their childbearing years. Cardiovascular disease is the leading cause of mortality in this patient population at an age when women often have low cardiovascular risk. Hypertension is a major cardiovascular disease risk factor, and its prevalence is markedly increased in women with SLE. Estrogen has traditionally been implicated in SLE disease progression because of the prevalence of the disease in women; however, its role in cardiovascular risk factors such as hypertension is unclear. The objective of this review is to discuss evidence for the role of estrogen in both human and murine SLE with emphasis on the effect of estrogen on cardiovascular risk factors, including hypertension. Methods PubMed was used to search for articles with terms related to estradiol and SLE. The references of retrieved publications were also reviewed. Findings The potential permissive role of estrogen in SLE development is supported by studies from experimental animal models of lupus in which early removal of estrogen or its effects leads to attenuation of SLE disease parameters, including autoantibody production and renal injury. However, data about the role of estrogens in human SLE are much less clear, with most studies not reaching firm conclusions about positive or negative outcomes after hormonal manipulations involving estrogen during SLE (ie, oral contraceptives, hormone therapy). Significant gaps in knowledge remain about the effect of estrogen on cardiovascular risk factors during SLE. Studies in women with SLE were not designed to determine the effect of estrogen or hormone therapy on blood pressure even though hypertension is highly prevalent, and risk of premature ovarian failure could necessitate use of hormone therapy in women with SLE. Recent evidence from an experimental animal model of lupus found that estrogen may protect against

  13. Potential mechanisms underlying estrogen-induced expression of the molluscan estrogen receptor (ER) gene

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Thi Kim Anh [School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308 (Australia); Department of Agriculture, Forestry and Fisheries, Vinh University, 182 Le Duan St., Vinh City, Nghe An (Viet Nam); MacFarlane, Geoff R. [School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308 (Australia); Kong, Richard Yuen Chong [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong Special Administrative Region (China); O’Connor, Wayne A. [New South Wales Department of Primary Industries, Port Stephens Fisheries Institute, Taylors Beach, NSW 2316 (Australia); Yu, Richard Man Kit, E-mail: Richard.Yu@newcastle.edu.au [School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308 (Australia)

    2016-10-15

    Highlights: • This is the first report on the putative promoter sequence of a molluscan ER gene. • The gene promoter contains putative binding sites for direct and indirect interaction with ER. • E2 upregulates ER gene expression in the ovary in vitro and in vivo. • E2-induced gene expression may require a novel ligand-dependent receptor. • The ER proximal promoter is hypomethylated regardless of gene expression levels. - Abstract: In vertebrates, estrogens and estrogen mimicking chemicals modulate gene expression mainly through a genomic pathway mediated by the estrogen receptors (ERs). Although the existence of an ER orthologue in the mollusc genome has been known for some time, its role in estrogen signalling has yet to be deciphered. This is largely due to its constitutive (ligand-independent) activation and a limited mechanistic understanding of its regulation. To fill this knowledge gap, we cloned and characterised an ER cDNA (sgER) and the 5′-flanking region of the gene from the Sydney rock oyster Saccostrea glomerata. The sgER cDNA is predicted to encode a 477-amino acid protein that contains a DNA-binding domain (DBD) and a ligand-binding domain (LBD) typically conserved among both vertebrate and invertebrate ERs. A comparison of the sgER LBD sequence with those of other ligand-dependent ERs revealed that the sgER LBD is variable at several conserved residues known to be critical for ligand binding and receptor activation. Ligand binding assays using fluorescent-labelled E2 and purified sgER protein confirmed that sgER is devoid of estrogen binding. In silico analysis of the sgER 5′-flanking sequence indicated the presence of three putative estrogen responsive element (ERE) half-sites and several putative sites for ER-interacting transcription factors, suggesting that the sgER promoter may be autoregulated by its own gene product. sgER mRNA is ubiquitously expressed in adult oyster tissues, with the highest expression found in the ovary

  14. Estrogen deficiency heterogeneously affects tissue specific stem cells in mice

    Science.gov (United States)

    Kitajima, Yuriko; Doi, Hanako; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Kitajima, Michio; Miura, Kiyonori; Li, Tao-Sheng; Masuzaki, Hideaki

    2015-01-01

    Postmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17β-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17β-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type colonies in vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growth in vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders. PMID:26245252

  15. Reviewing the options for local estrogen treatment of vaginal atrophy

    Directory of Open Access Journals (Sweden)

    Lindahl SH

    2014-03-01

    Full Text Available Sarah H Lindahl Sutter East Bay Medical Foundation, SEBMF – Diablo Division, Castro Valley, CA, USA Background: Vaginal atrophy is a chronic condition with symptoms that include vaginal dryness, pain during sex, itching, irritation, burning, and discharge, as well as various urinary problems. Up to 45% of postmenopausal women may be affected, but it often remains underreported and undertreated. This article aims to review the current recommendations for treatment of vaginal atrophy, and current data on the effectiveness and safety of local vaginal estrogen therapies. Methods: Literature regarding vaginal atrophy (2007–2012 was retrieved from PubMed and summarized, with emphasis on data related to the treatment of vaginal atrophy with local vaginal estrogen therapy. Results: Published data support the effectiveness and endometrial safety of low-dose local estrogen therapies. These results further support the general recommendation by the North American Menopause Society that a progestogen is not needed for endometrial protection in patients using low-dose local vaginal estrogen. Benefits of long-term therapy for vaginal atrophy include sustained relief of symptoms as well as physiological improvements (eg, decreased vaginal pH and increased blood flow, epithelial thickness, secretions. Conclusion: Currently available local vaginal estrogen therapies are well tolerated and effective in relieving symptoms of vaginal atrophy. Recent data support the endometrial safety of low-dose regimens for up to 1 year. Keywords: menopause, estrogen, local estrogen therapy, vaginal atrophy

  16. Estrogenic effects of marijuana smoke condensate and cannabinoid compounds

    International Nuclear Information System (INIS)

    Lee, Soo Yeun; Oh, Seung Min; Chung, Kyu Hyuck

    2006-01-01

    Chronic exposure to marijuana produces adverse effects on the endocrine and reproductive systems in humans; however, the experimental evidence for this presented thus far has not been without controversy. In this study, the estrogenic effect of marijuana smoke condensate (MSC) was evaluated using in vitro bioassays, viz., the cell proliferation assay, the reporter gene assay, and the ER competitive binding assay. The results of these assays were compared with those of three major cannabinoids, i.e., THC, CBD, and CBN. The estrogenic effect of MSC was further confirmed by the immature female rat uterotrophic assay. MSC stimulated the estrogenicity related to the ER-mediated pathway, while neither THC, CBD, nor CBN did. Moreover, treatment with 10 and 25 mg/kg MSC induced significant uterine response, and 10 mg/kg MSC resulted in an obvious change in the uterine epithelial cell appearance. MSC also enhanced the IGFBP-1 gene expression in a dose-dependent manner. To identify the constituents of MSC responsible for its estrogenicity, the MSC fractionated samples were examined using another cell proliferation assay, and the estrogenic active fraction was analyzed using GC-MS. In the organic acid fraction that showed the strongest estrogenic activity among the seven fractions of MSC, phenols were identified. Our results suggest that marijuana abuse is considered an endocrine-disrupting factor. Furthermore, these results suggest that the phenolic compounds contained in MSC play a role in its estrogenic effect

  17. The role of estrogen in cutaneous ageing and repair.

    Science.gov (United States)

    Wilkinson, Holly N; Hardman, Matthew J

    2017-09-01

    Combined advances in modern medical practice and increased human longevity are driving an ever-expanding elderly population. Females are particularly at risk of age-associated pathology, spending more of their lives in a post-menopausal state. Menopause, denoted by a rapid decline in serum sex steroid levels, accelerates biological ageing across the body's tissues. Post-menopause physiological changes are particularly noticeable in the skin, which loses structural architecture and becomes prone to damage. The sex steroid most widely discussed as an intrinsic contributor to skin ageing and pathological healing is 17β-estradiol (or estrogen), although many others are involved. Estrogen deficiency is detrimental to many wound-healing processes, notably inflammation and re-granulation, while exogenous estrogen treatment widely reverses these effects. Over recent decades, many of the molecular and cellular correlates to estrogen's beneficial effect on normal skin homeostasis and wound healing have been reported. However, disparities still exist, particularly in the context of mechanistic studies investigating estrogen receptor signalling and its potential cellular effects. New molecular techniques, coupled with increased understanding of estrogen in skin biology, will provide further opportunities to develop estrogen receptor-targeted therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Glyphosate induces human breast cancer cells growth via estrogen receptors.

    Science.gov (United States)

    Thongprakaisang, Siriporn; Thiantanawat, Apinya; Rangkadilok, Nuchanart; Suriyo, Tawit; Satayavivad, Jutamaad

    2013-09-01

    Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. The in vivo estrogenic and in vitro anti-estrogenic activity of permethrin and bifenthrin.

    Science.gov (United States)

    Brander, Susanne M; He, Guochun; Smalling, Kelly L; Denison, Michael S; Cherr, Gary N

    2012-12-01

    Pyrethroids are highly toxic to fish at parts per billion or parts per trillion concentrations. Their intended mechanism is prolonged sodium channel opening, but recent studies reveal that pyrethroids such as permethrin and bifenthrin also have endocrine activity. Additionally, metabolites may have greater endocrine activity than parent compounds. The authors evaluated the in vivo concentration-dependent ability of bifenthrin and permethrin to induce choriogenin (an estrogen-responsive protein) in Menidia beryllina, a fish species known to reside in pyrethroid-contaminated aquatic habitats. The authors then compared the in vivo response with an in vitro assay--chemical activated luciferase gene expression (CALUX). Juvenile M. beryllina exposed to bifenthrin (1, 10, 100 ng/L), permethrin (0.1, 1, 10 µg/L), and ethinylestradiol (1, 10, 50 ng/L) had significantly higher ng/mL choriogenin (Chg) measured in whole body homogenate than controls. Though Chg expression in fish exposed to ethinylestradiol (EE2) exhibited a traditional sigmoidal concentration response, curves fit to Chg expressed in fish exposed to pyrethroids suggest a unimodal response, decreasing slightly as concentration increases. Whereas the in vivo response indicated that bifenthrin and permethrin or their metabolites act as estrogen agonists, the CALUX assay demonstrated estrogen antagonism by the pyrethroids. The results, supported by evidence from previous studies, suggest that bifenthrin and permethrin, or their metabolites, appear to act as estrogen receptor (ER) agonists in vivo, and that the unmetabolized pyrethroids, particularly bifenthrin, act as an ER antagonists in cultured mammalian cells. Copyright © 2012 SETAC.

  20. The in vivo estrogenic and in vitro anti-estrogenic activity of permethrin and bifenthrin

    OpenAIRE

    Brander, Susanne M.; He, Guochun; Smalling, Kelly L.; Denison, Michael S.; Cherr, Gary N.

    2012-01-01

    Pyrethroids are highly toxic to fish at parts per billion or parts per trillion concentrations. Their intended mechanism is prolonged sodium channel opening, but recent studies reveal that pyrethroids such as permethrin and bifenthrin also have endocrine activity. Additionally, metabolites may have greater endocrine activity than parent compounds. We evaluated the in vivo concentration-dependent ability of bifenthrin and permethrin to induce choriogenin (an estrogen-responsive protein) in Men...

  1. Radical-scavenging Activity of Estrogen and Estrogen-like Compounds Using the Induction Period Method

    Directory of Open Access Journals (Sweden)

    Seiichiro Fujisawa

    2007-04-01

    Full Text Available The radical-scavenging activity of estrogens (estrone, 2-hydroxyestradiol,estrogen-like compounds (diethylstilbestrol, DES; bisphenol A, BPA and the mono-phenolic compound 2,6-di-t-butyl-4-methoxyphenol (BMP was investigated using themethod of measuring the induction period for polymerization of methyl methacrylate(MMA initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN andbenzoyl peroxide (BPO at 70°C using differential scanning calorimetry (DSC. Thestoichiometric factor (n, number of free radicals trapped by one mole of antioxidantmoiety for the AIBN system declined in the order BMP (2.0, 2-hydroxyestradiol (2.0>DES (1.3 > BPA (1.2 > estrone (0.9, whereas that for the BPO system declined in theorder BMP (2.0 >DES (1.9, BPA (1.9 > estrone (1.3 > 2-hydroxyestradiol (0.7. Theinhibition rate constant (kinh x 10-3 M-1s-1 for the AIBN system declined in the orderestrone (2.2 > BPA (2.0 > DES (1.9 > 2-hydroxyestradiol (1.2 > BMP (1.1, whereasthat for the BPO system declined in the order 2-hydroxyestradiol (3.2 > estrone (1.4 >DES (1.2 > BPA (1.0 > BMP (0.9. The radical-scavenging activity for bioactivecompounds such as estrogens should be evaluated using these two methods (the n and kinhto elucidate the mechanism of a particular reaction. The great difference of the n and kinhfor estrogens between the AIBN and BPO system suggested that their oxidation process iscomplex.

  2. Estrogen Inhibits Dlk1/FA1 Production: A Potential Mechanism for Estrogen Effects on Bone Turnover

    Science.gov (United States)

    Abdallah, B. M.; Bay-Jensen, A.; Srinivasan, B.; Tabassi, N. C.; Garnero, P.; Delaissé, J.; Khosla, S.; Kassem, M.

    2011-01-01

    We have recently identified Dlk1/FA1 (Delta-like 1/FA1) as a novel regulator of bone mass that functions to mediate bone loss, under estrogen deficiency, in mice. In this report, we investigated the effects of estrogen (E)-deficiency and E replacement on serum (s) levels of Dlk1/FA1 (s-Dlk1FA1) and its correlation with bone turnover markers. s-Dlk1/FA1 and bone turnover markers (s-CTx and s-osteocalcin), were measured in two cohorts: a group of pre- and postmenopausal women (n=100) and a group of postmenopausal women, where half had received estrogen replacement therapy (ERT) (n=166). s-Dlk1/FA1, and s-CTX were elevated in postmenopausal E-deficient compared to premenopausal E-replete women (both; P<0.001). s-Dlk1/FA1 was correlated with s-CTX (r=0.30, P<0.01). ERT, in postmenopausal women, decreased s-Dlk1/FA1, as well as s-CTX and s-osteoclacin (all; P<0.0001). Changes in s-Dlk1 were significantly correlated with those observed in s-CTx (r=0.18, P<0.05) and s-osteocalcin (r=0.28, P<0.001). In conclusion, s-Dlk1/FA1 is influenced by E-deficiency and is correlated with bone turnover. Increased levels of s-Dlk1/FA1 in post-menopausal women may be a mechanism mediating the effects estrogen deficiency on bone turnover. PMID:21681814

  3. Functional adaptation in female rats: the role of estrogen signaling.

    Directory of Open Access Journals (Sweden)

    Susannah J Sample

    Full Text Available Sex steroids have direct effects on the skeleton. Estrogen acts on the skeleton via the classical genomic estrogen receptors alpha and beta (ERα and ERβ, a membrane ER, and the non-genomic G-protein coupled estrogen receptor (GPER. GPER is distributed throughout the nervous system, but little is known about its effects on bone. In male rats, adaptation to loading is neuronally regulated, but this has not been studied in females.We used the rat ulna end-loading model to induce an adaptive modeling response in ovariectomized (OVX female Sprague-Dawley rats. Rats were treated with a placebo, estrogen (17β-estradiol, or G-1, a GPER-specific agonist. Fourteen days after OVX, rats underwent unilateral cyclic loading of the right ulna; half of the rats in each group had brachial plexus anesthesia (BPA of the loaded limb before loading. Ten days after loading, serum estrogen concentrations, dorsal root ganglion (DRG gene expression of ERα, ERβ, GPER, CGRPα, TRPV1, TRPV4 and TRPA1, and load-induced skeletal responses were quantified. We hypothesized that estrogen and G-1 treatment would influence skeletal responses to cyclic loading through a neuronal mechanism. We found that estrogen suppresses periosteal bone formation in female rats. This physiological effect is not GPER-mediated. We also found that absolute mechanosensitivity in female rats was decreased, when compared with male rats. Blocking of adaptive bone formation by BPA in Placebo OVX females was reduced.Estrogen acts to decrease periosteal bone formation in female rats in vivo. This effect is not GPER-mediated. Gender differences in absolute bone mechanosensitivity exist in young Sprague-Dawley rats with reduced mechanosensitivity in females, although underlying bone formation rate associated with growth likely influences this observation. In contrast to female and male rats, central neuronal signals had a diminished effect on adaptive bone formation in estrogen-deficient female rats.

  4. Environmental estrogen(s) induced swimming behavioural alterations in adult zebrafish (Danio rerio).

    Science.gov (United States)

    Goundadkar, Basavaraj B; Katti, Pancharatna

    2017-09-01

    The present study is an attempt to investigate the effects of long-term (75days) exposure to environmental estrogens (EE) on the swimming behaviour of zebrafish (Danio rerio). Adult zebrafish were exposed semi-statically to media containing commonly detected estrogenic water contaminants (EE2, DES and BPA) at a concentration (5ng/L) much lower than environmentally recorded levels. Time spent in swimming, surface preference, patterns and path of swimming were recorded (6mins) for each fish using two video cameras on day 15, 30 60 and 75. Video clips were analysed using a software program. Results indicate that chronic exposure to EE leads to increased body weight and size of females, reduced (Pswimming time, delay in latency, increased (P<0.05) immobility, erratic movements and freezing episodes. We conclude that estrogenic contamination of natural aquatic systems induces alterations in locomotor behaviour and associated physiological disturbances in inhabitant fish fauna. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Estrogenic and anti-estrogenic activity of off-the-shelf hair and skin care products.

    Science.gov (United States)

    Myers, Sharon L; Yang, Chun Z; Bittner, George D; Witt, Kristine L; Tice, Raymond R; Baird, Donna D

    2015-05-01

    Use of personal care products is widespread in the United States but tends to be greater among African Americans than whites. Of special concern is the possible hazard of absorption of chemicals with estrogenic activity (EA) or anti-EA (AEA) in these products. Such exposure may have adverse health effects, especially when it occurs during developmental windows (e.g., prepubertally) when estrogen levels are low. We assessed the ethanol extracts of eight commonly used hair and skin products popular among African Americans for EA and AEA using a cell proliferation assay with the estrogen sensitive MCF-7:WS8 cell line derived from a human breast cancer. Four of the eight personal care products tested (Oil Hair Lotion, Extra-dry Skin Lotion, Intensive Skin Lotion, Petroleum Jelly) demonstrated detectable EA, whereas three (Placenta Hair Conditioner, Tea-Tree Hair Conditioner, Cocoa Butter Skin Cream) exhibited AEA. Our data indicate that hair and skin care products can have EA or AEA, and suggest that laboratory studies are warranted to investigate the in vivo activity of such products under chronic exposure conditions as well as epidemiologic studies to investigate potential adverse health effects that might be associated with use of such products.

  6. Participation of Water in the Binding of Estrogen Receptor with Estrogen Responsive Element in vitro.

    Science.gov (United States)

    Zhu, Guo-Zhang; Tang, Guo-Qing; Ruan, Kang-Cheng; Gong, Yue-Ting; Zhang, Yong-Lian

    1998-01-01

    Many reports have showed that bound water was involved in the interaction between/among the macromolecules. However, it has not been reported whether bound water is also involved in the binding of trans-factors and cis-elements in the regulation of the eukaryotic gene trans-cription or not. Preliminary studies have been made on the effect of bound water on the binding of estrogen receptor with estrogen responsive element in vitro. In the gel retardation assay using the cytosol extract of rat uterus as the supplier of estrogen receptor and 32 bp oligonucleotide containing a concensus vitellogenin A(2) ERE as the probe, various cosolvents, such as glycerol, sucrose, N-dimethylformamide and dimethylsulfoxide, were added respectively to the reaction mixture in varying concentrations to regulate the osmotic pressure. The results indicated that the binding of ER-ERE was enhanced with the increase in the final concentration of these individual cosolvents. On the other hand, when the reaction was carried out under an increasing hydrostatic pressure, the ER-ERE binding was decreased sharply. After decompression the binding of ER-ERE was gradually restored to the normal level with the lapse of time. These results suggested that bound water was directly involved in the binding of ER-ERE and may play an important role in the regulation of the eukaryotic gene transcription.

  7. Hpm of Estrogen Model on the Dynamics of Breast Cancer

    Science.gov (United States)

    Govindarajan, A.; Balamuralitharan, S.; Sundaresan, T.

    2018-04-01

    We enhance a deterministic mathematical model involving universal dynamics on breast cancer with immune response. This is population model so includes Normal cells class, Tumor cells, Immune cells and Estrogen. The eects regarding Estrogen are below incorporated in the model. The effects show to that amount the arrival of greater Estrogen increases the danger over growing breast cancer. Furthermore, approximate solution regarding nonlinear differential equations is arrived by Homotopy Perturbation Method (HPM). Hes HPM is good and correct technique after solve nonlinear differential equation directly. Approximate solution learnt with the support of that method is suitable same as like the actual results in accordance with this models.

  8. CERAPP: Collaborative estrogen receptor activity prediction project

    DEFF Research Database (Denmark)

    Mansouri, Kamel; Abdelaziz, Ahmed; Rybacka, Aleksandra

    2016-01-01

    ). Risk assessors need tools to prioritize chemicals for evaluation in costly in vivo tests, for instance, within the U.S. EPA Endocrine Disruptor Screening Program. oBjectives: We describe a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project...... States and Europe to predict ER activity of a common set of 32,464 chemical structures. Quantitative structure-activity relationship models and docking approaches were employed, mostly using a common training set of 1,677 chemical structures provided by the U.S. EPA, to build a total of 40 categorical......: Individual model scores ranged from 0.69 to 0.85, showing high prediction reliabilities. Out of the 32,464 chemicals, the consensus model predicted 4,001 chemicals (12.3%) as high priority actives and 6,742 potential actives (20.8%) to be considered for further testing. conclusion: This project demonstrated...

  9. Estrogens can disrupt amphibian mating behavior.

    Directory of Open Access Journals (Sweden)

    Frauke Hoffmann

    Full Text Available The main component of classical contraceptives, 17α-ethinylestradiol (EE2, has high estrogenic activity even at environmentally relevant concentrations. Although estrogenic endocrine disrupting compounds are assumed to contribute to the worldwide decline of amphibian populations by adverse effects on sexual differentiation, evidence for EE2 affecting amphibian mating behaviour is lacking. In this study, we demonstrate that EE2 exposure at five different concentrations (0.296 ng/L, 2.96 ng/L, 29.64 ng/L, 2.96 µg/L and 296.4 µg/L can disrupt the mating behavior of adult male Xenopus laevis. EE2 exposure at all concentrations lowered male sexual arousal, indicated by decreased proportions of advertisement calls and increased proportions of the call type rasping, which characterizes a sexually unaroused state of a male. Additionally, EE2 at all tested concentrations affected temporal and spectral parameters of the advertisement calls, respectively. The classical and highly sensitive biomarker vitellogenin, on the other hand, was only induced at concentrations equal or higher than 2.96 µg/L. If kept under control conditions after a 96 h EE2 exposure (2.96 µg/L, alterations of male advertisement calls vanish gradually within 6 weeks and result in a lower sexual attractiveness of EE2 exposed males toward females as demonstrated by female choice experiments. These findings indicate that exposure to environmentally relevant EE2 concentrations can directly disrupt male mate calling behavior of X. laevis and can indirectly affect the mating behavior of females. The results suggest the possibility that EE2 exposure could reduce the reproductive success of EE2 exposed animals and these effects might contribute to the global problem of amphibian decline.

  10. Channel catfish (Ictalurus punctatus) leukocytes express estrogen receptor isoforms ERα and ERβ2 and are functionally modulated by estrogens.

    Science.gov (United States)

    Iwanowicz, Luke R; Stafford, James L; Patiño, Reynaldo; Bengten, Eva; Miller, Norman W; Blazer, Vicki S

    2014-09-01

    Estrogens are recognized as modulators of immune responses in mammals and teleosts. While it is known that the effects of estrogens are mediated via leukocyte-specific estrogen receptors (ERs) in humans and mice, leucocyte-specific estrogen receptor expression and the effects of estrogens on this cell population is less explored and poorly understood in teleosts. Here in, we verify that channel catfish (Ictalurus punctaus) leukocytes express ERα and ERβ2. Transcripts of these isoforms were detected in tissue-associated leukocyte populations by PCR, but ERβ2 was rarely detected in PBLs. Expression of these receptors was temporally regulated in PBLs following polyclonal activation by concanavalin A, lipopolysaccharide or alloantigen based on evaluation by quantitative and end-point PCR. Examination of long-term leukocyte cell lines demonstrated that these receptors are differentially expressed depending on leukocyte lineage and phenotype. Expression of ERs was also temporally dynamic in some leukocyte lineages and may reflect stage of cell maturity. Estrogens affect the responsiveness of channel catfish peripheral blood leukocytes (PBLs) to mitogens in vitro. Similarly, bactericidal activity and phorbol 12-myristate 13-acetate induced respiratory burst was modulated by 17β-estradiol. These actions were blocked by the pure ER antagonist ICI 182780 indicating that response is, in part, mediated via ERα. In summary, estrogen receptors are expressed in channel catfish leukocytes and participate in the regulation of the immune response. This is the first time leukocyte lineage expression has been reported in teleost cell lines. Published by Elsevier Ltd.

  11. Estrogen regulation of chicken riboflavin carrier protein gene is mediated by ERE half sites without direct binding of estrogen receptor.

    Science.gov (United States)

    Bahadur, Urvashi; Ganjam, Goutham K; Vasudevan, Nandini; Kondaiah, Paturu

    2005-02-28

    Estrogen is an important steroid hormone that mediates most of its effects on regulation of gene expression by binding to intracellular receptors. The consensus estrogen response element (ERE) is a 13bp palindromic inverted repeat with a three nucleotide spacer. However, several reports suggest that many estrogen target genes are regulated by diverse elements, such as imperfect EREs and ERE half sites (ERE 1/2), which are either the proximal or the distal half of the palindrome. To gain more insight into ERE half site-mediated gene regulation, we used a region from the estrogen-regulated chicken riboflavin carrier protein (RCP) gene promoter that contains ERE half sites. Using moxestrol, an analogue of estrogen and transient transfection of deletion and mutation containing RCP promoter/reporter constructs in chicken hepatoma (LMH2A) cells, we identified an estrogen response unit (ERU) composed of two consensus ERE 1/2 sites and one non-consensus ERE 1/2 site. Mutation of any of these sites within this ERU abolishes moxestrol response. Further, the ERU is able to confer moxestrol responsiveness to a heterologous promoter. Interestingly, RCP promoter is regulated by moxestrol in estrogen responsive human MCF-7 cells, but not in other cell lines such as NIH3T3 and HepG2 despite estrogen receptor-alpha (ER-alpha) co transfection. Electrophoretic mobility shift assays (EMSAs) with promoter regions encompassing the half sites and nuclear extracts from LMH2A cells show the presence of a moxestrol-induced complex that is abolished by a polyclonal anti-ERalpha antibody. Surprisingly, estrogen receptor cannot bind to these promoter elements in isolation. Thus, there appears to be a definite requirement for some other factor(s) in addition to estrogen receptor, for the generation of a suitable response of this promoter to estrogen. Our studies therefore suggest a novel mechanism of gene regulation by estrogen, involving ERE half sites without direct binding of ER to the

  12. Determination of diffusion coefficients in Au/Ni thin films by Auger electron spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Abdul-Lettif, Ahmed M. [Physics Department, College of Science, Babylon University, Hilla (Iraq)

    2004-07-01

    Interdiffusion in vacuum-deposited Au/Ni thin films at temperatures in the range 200-500 C has been investigated using the Auger depth profiling technique and X-ray diffraction analysis. A modified Wipple model was used to determine the diffusion coefficients of Ni in Au to be 5.3 x 10{sup -16} cm{sup 2}/s at 500 C, 4.0 x 10{sup -17} cm{sup 2}/s at 400 C, 2.5 x 10{sup -18} cm{sup 2}/s at 300 C, and 1.2 x 10{sup -19} cm{sup 2}/s at 200 C. An activation energy of 0.87 eV was calculated. The present diffusion data differ significantly from the corresponding values extracted by some other investigators and the reasons for this disagreement were discussed. (copyright 2004 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  13. 135La as an Auger-electron emitter for targeted internal radiotherapy

    Science.gov (United States)

    Fonslet, J.; Lee, B. Q.; Tran, T. A.; Siragusa, M.; Jensen, M.; Kibédi, T.; E Stuchbery, A.; Severin, G. W.

    2018-01-01

    135La has favorable nuclear and chemical properties for Auger-based targeted internal radiotherapy. Here we present detailed investigations of the production, emissions, and dosimetry related to 135La therapy. 135La was produced by 16.5 MeV proton irradiation of metallic natBa on a medical cyclotron, and was isolated and purified by trap-and-release on weak cation-exchange resin. The average production rate was 407  ±  19 MBq µA-1 (saturation activity), and the radionuclidic purity was 98% at 20 h post irradiation. Chemical separation recovered  >  98 % of the 135La with an effective molar activity of 70  ±  20 GBq µmol-1. To better assess cellular and organ dosimetry of this nuclide, we have calculated the x-ray and Auger emission spectra using a Monte Carlo model accounting for effects of multiple vacancies during the Auger cascade. The generated Auger spectrum was used to calculate cellular S-factors. 135La was produced with high specific activity, reactivity, radionuclidic purity, and yield. The emission spectrum and the dosimetry are favorable for internal radionuclide therapy.

  14. Comments on Auger electron production by Ne/sup +/ bombardment of surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Pepper, S V; Ferrante, J [National Aeronautics and Space Administration, Cleveland, OH (USA). Lewis Research Center

    1979-09-01

    In this letter, the authors first report rather conclusive experimental evidence showing that the Ne Auger signal is due to asymmetric Ne-metal collisions and not symmetric Ne-Ne collisions. Next it is shown that the Ne Auger signal is in fact observable by Ne/sup +/ bombardment of Si and with signal strength comparable to that of the Si Auger signal for 3 keV incident ion energy. Finally, they comment on some trends in the relative amplitudes of the 21.9 and 25.1 eV Ne Auger signals as a function of incident ion energy and target species.

  15. Ellipticine-aimed polymer-conjugated Auger electron emitter: multistage organelle targeting approach

    Czech Academy of Sciences Publication Activity Database

    Sedláček, Ondřej; Hrubý, Martin; Studenovský, Martin; Kučka, Jan; Větvička, David; Kovář, Lubomír; Říhová, Blanka; Ulbrich, Karel

    2011-01-01

    Roč. 22, č. 6 (2011), s. 1194-1201 ISSN 1043-1802 R&D Projects: GA ČR GPP207/10/P054; GA ČR GAP108/10/1560; GA AV ČR IAAX00500803; GA MŠk 1M0505 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z50200510 Keywords : ellipticine * drug delivery * radiotherapy Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.930, year: 2011

  16. Modification to an Auger Electron Spectroscopy system for measuring segregation in a bi-crystal

    CSIR Research Space (South Africa)

    Jafta, CJ

    2013-03-01

    Full Text Available . Parameters like temperature measurement, crystal history and spectrometer variables are all adding to the complexity of directly comparing the segregation behaviour from one crystal to another. This investigation makes use of a Cu bi-crystal, modifications...

  17. Modification to an Auger Electron Spectroscopy system for measuring segregation in a bi-crystal

    International Nuclear Information System (INIS)

    Jafta, C J; Roos, W D; Terblans, J J

    2013-01-01

    It is reported that different crystal surface orientations yield different segregation fluxes. Although there were a few attempts to confirm these predictions experimentally, it is very difficult to compare data without making a few assumptions. Parameters like temperature measurement, crystal history and spectrometer variables are all adding to the complexity of directly comparing the segregation behaviour from one crystal to another. This investigation makes use of a Cu bi-crystal, modifications to the scanning control unit of the AES electron beam to eliminate the difference in experimental parameters and specialized written software to automate the data acquisition process. This makes direct comparison of segregation parameters on two different orientations possible. The paper describes the electron beam modifications, experimental setup and procedures, as well as the software developed to control the electron beam and automate data acquisition.

  18. Accelerator based Production of Auger-Electron-emitting Isotopes for Radionuclide Therapy

    DEFF Research Database (Denmark)

    Thisgaard, Helge

    Sb from the enriched 119Sn target material with high radionuclidic- and chemical purity. A method that also allows efficient recovery of the 119Sn for recycling. To demonstrate the ability of producing therapeutic quantities of 119Sb and other radioisotopes for therapy with a low-energy cyclotron...... isotopes (e.g. 119Sb or 64Cu) using the PETtrace cyclotron commonly found at the larger PET-centers in the hospitals. Finally, research in a new method to measure the radiotoxicity of Auger-emitters invitro using cellular microinjection has been carried out. The purpose of this method is to be able...

  19. High energy resolution and first time-dependent positron annihilation induced Auger electron spectroscopty

    International Nuclear Information System (INIS)

    Mayer, Jakob

    2010-01-01

    It was the aim of this thesis to improve the existing positron annihilation induced Auger spectrometer at the highly intense positron source NEPOMUC (NEutron induced POsitron source MUniCh) in several ways: Firstly, the measurement time for a single spectrum should be reduced from typically 12 h to roughly 1 h or even less. Secondly, the energy resolution, which amounted to ΔE/E∼10%, should be increased by at least one order of magnitude in order to make high resolution positron annihilation induced Auger spectroscopy (PAES)-measurements of Auger transitions possible and thus deliver more information about the nature of the Auger process. In order to achieve these objectives, the PAES spectrometer was equipped with a new electron energy analyzer. For its ideal operation all other components of the Auger analysis chamber had to be adapted. Particularly the sample manipulation and the positron beam guidance had to be renewed. Simulations with SIMION registered ensured the optimal positron lens parameters. After the adjustment of the new analyzer and its components, first measurements illustrated the improved performance of the PAES setup: Firstly, the measurement time for short overview measurements was reduced from 3 h to 420 s. The measurement time for more detailed Auger spectra was shortened from 12 h to 80 min. Secondly, even with the reduced measurement time, the signal to noise ratio was also enhanced by one order of magnitude. Finally, the energy resolution was improved to ΔE/E 2,3 VV-transition with PAES. Thus, within this thesis two objectives were achieved: Firstly, the PAES spectrometer was renewed and improved by at least one order of magnitude with respect to the signal to noise ratio, the measurement time and the energy resolution. Secondly, several measurements have been carried out, demonstrating the high performance of the spectrometer. Amongst them are first dynamic PAES measurements and a high resolution measurement of the CuM 2,3 VV-transition. (orig.)

  20. Modelling of radiation risk induced by radon and sources of Auger electrons

    International Nuclear Information System (INIS)

    Boem, R.

    2003-01-01

    This thesis follows the national and worldwide radon research and application Auger radionuclides in nuclear medicine. Results of this thesis can be summarised into several points: (1) For the prediction of cancer risk following the exposure, it is also necessary to consider the mean cycle time of target cells. From our analyses it can be concluded that the mean cycle time of target cells should exceed 100 days. (2) The value of excess relative risk is for smokers ERR/WLM = (2.4-4.1)x10 -3 WLM -1 and that of the nonsmokers ERR/WLM=(4.2-10.7)x10 -3 WLM -1 , considering the underground medium. Excess relative risk for the nonsmokers ERR/(Bq m -3 ) = (1.0-3.5) Bq -1 m 3 and for smokers ERR/(Bq m -3 ) = (0.3-1.2) 10 -3 Bq -1 m 3 is supposed in dwellings. (3) Microdosimetric models are very helpful and suitable for prediction of the radon risk for underground conditions, as well as for indoor radon risk evaluation and they are also able to take into account the influence of the smoking habit. (4) The spatial distribution of energy deposition events and their magnitude is an essential input to evaluate the effects of radiation on biological systems. Therefore, for the calculation of deposited energy from the DNA incorporated Auger emitters, it is necessary at the DNA level to employ the MC calculation. In an effort to save computer time and memory it is possible to use the fitted function for monoenergetic electrons for estimation of at least relative radiotoxicity. The value of energy deposited in a small volume (sphere of diameter 2 nm) can be considered as the first estimation of an Auger emitter's radiotoxicity. (author)

  1. Energy analyzer for Auger electron spectroscopy and low-energy backscattering ion spectroscopy

    International Nuclear Information System (INIS)

    Volkov, S.S.; Gorelik, V.A.; Gutenko, V.T.; Protopopov, O.D.; Trubitsin, A.A.; Shuvalova, Z.A.; Yakushev, G.A.

    1988-01-01

    Energy analyzer for electron Auger spectroscopy and low-energy backscattering ion spectroscopy is described. Analyzer presents one-cascade variant of cylindrical mirror with second-order focusing. Energy relative resolution is continuously adjusted within 0.2-1.2% limits. Signal/noise relation by Cu Auger-line at 1 muA current of exciting beam changes upper limit of range 150-450

  2. 135La as an auger-electron emitter for targeted internal radiotherapy

    DEFF Research Database (Denmark)

    Fonslet, Jesper; Lee, Boon Quan; Tran, Thuy A.

    2018-01-01

    Introduction: 135La has favorable nuclear and chemical properties for Auger-based targeted internal radiotherapy. Here we present detailed investigations of the production, emissions, imaging characteristics, and dosimetry related to 135La therapy. Methods and Results: 135La was produced by 16.5 Me....... The generated Auger spectrum was used to recalculate cellular S-factors. Conclusion: 135La was produced with high specific activity, reactivity, radionuclidic purity, and yield. The emission spectrum and the dosimetry are favorable for internal radionuclide therapy. ....... recovered > 98 % of the 135La with an effective molar activity of 70 ±20 GBq/µmol. To better assess cellular and organ dosimetry of this nuclide, we have recalculated the X-ray and Auger emission spectra using a Monte Carlo model accounting for effects of multiple vacancies during the Auger cascade...

  3. The KLM plus KLN Auger electron spectrum of rubidium in different matrices

    Czech Academy of Sciences Publication Activity Database

    Inoyatov, A. K.; Kovalík, Alojz; Perevoshchikov, L. L.; Filosofov, D. V.; Vénos, Drahoslav; Lee, B. Q.; Ekman, J.; Baimukhanova, A.

    2017-01-01

    Roč. 50, č. 15 (2017), č. článku 155001. ISSN 0953-4075 R&D Projects: GA ČR(CZ) GAP203/12/1896; GA MŠk LG14004 Institutional support: RVO:61389005 Keywords : Rb-85 * Sr-85 * KLM- * KLN-Auger transitions * atomic environment * chemical shift * multiconfiguration Dirac-Hartree-Fock calculations Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders OBOR OECD: Nuclear physics Impact factor: 1.792, year: 2016

  4. Estrogenic involvement in social learning, social recognition and pathogen avoidance.

    Science.gov (United States)

    Choleris, Elena; Clipperton-Allen, Amy E; Phan, Anna; Valsecchi, Paola; Kavaliers, Martin

    2012-04-01

    Sociality comes with specific cognitive skills that allow the proper processing of information about others (social recognition), as well as of information originating from others (social learning). Because sociality and social interactions can also facilitate the spread of infection among individuals the ability to recognize and avoid pathogen threat is also essential. We review here various studies primarily from the rodent literature supporting estrogenic involvement in the regulation of social recognition, social learning (socially acquired food preferences and mate choice copying) and the recognition and avoidance of infected and potentially infected individuals. We consider both genomic and rapid estrogenic effects involving estrogen receptors α and β, and G-protein coupled estrogen receptor 1, along with their interactions with neuropeptide systems in the processing of social stimuli and the regulation and expression of these various socially relevant behaviors. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. 21 CFR 862.1275 - Estrogens (total, nonpregnancy) test system.

    Science.gov (United States)

    2010-04-01

    ..., estradiol, and estriol) in plasma, serum, and urine of males and nonpregnant females. Measurement of... infertility, amenorrhea (absence of menses) differentiation of primary and secondary ovarian malfunction, estrogen secreting testicular and ovarian tumors, and precocious puberty in females. (b) Classification...

  6. Classical and Nonclassical Estrogen Receptor Action on Chromatin Templates

    National Research Council Canada - National Science Library

    Nordeen, Steven

    2000-01-01

    Improvement of hormone-based therapy in breast cancer and circumvention of its shortcomings is limited by the lack of detailed understanding of how steroids like estrogen work at a cellular and molecular level...

  7. Classical and Nonclassical Estrogen Receptor Action on Chromatin Templaces

    National Research Council Canada - National Science Library

    Nordeen, Steve

    2001-01-01

    Improvement of hormone-based therapy in breast cancer and circumvention of its shortcomings is limited by the lack of detailed understanding of how steroids like estrogen work at a cellular and molecular level...

  8. Bone turnover and oxidative stress markers in estrogen- deficient ...

    African Journals Online (AJOL)

    Bone turnover and oxidative stress markers in estrogen- ... reproduction in any medium, provided the original work is properly credited. ..... Institute for Laboratory Animal Research: Guide for the ... American Veterinary Medical Association.

  9. Role of estrogen receptor-α on food demand elasticity.

    Science.gov (United States)

    Minervini, Vanessa; Rowland, Neil E; Robertson, Kimberly L; Foster, Thomas C

    2015-05-01

    Estrogens have been shown to have an inhibitory effect on food intake under free-feeding conditions, yet the effects of estrogens on food-maintained operant responding have been studied to a much lesser extent and, thus, are not well understood. Therefore, the purpose of the present experiment was to use a behavioral economics paradigm to assess differences in demand elasticity between mice with knockout of the estrogen receptor subtype α, knockout of subtype β, and their wild type controls. The mice responded in a closed economy, and the price of food was increased by increasing the fixed-ratio response requirement every four sessions. Overall, we found that mice with the knockout of receptor subtype α had the most elastic demand functions. Therefore, under these conditions, estrogens increased food seeking via activation of the receptor subtype α. The results were inconsistent with those reported by previous studies that employed free-feeding conditions. © Society for the Experimental Analysis of Behavior.

  10. Original article Expression of Estrogen Alpha and Beta Receptors in ...

    African Journals Online (AJOL)

    mn

    Immunohistochemical Analysis ... Seven PCa cases contained foci of high-grade prostate intraepithelial neoplasia ... Immunohistochemistry was used to test the protein expression of ER-α and ER-β ... interactions of estrogens and ER as well.

  11. KBERG: KnowledgeBase for Estrogen Responsive Genes

    DEFF Research Database (Denmark)

    Tang, Suisheng; Zhang, Zhuo; Tan, Sin Lam

    2007-01-01

    Estrogen has a profound impact on human physiology affecting transcription of numerous genes. To decipher functional characteristics of estrogen responsive genes, we developed KnowledgeBase for Estrogen Responsive Genes (KBERG). Genes in KBERG were derived from Estrogen Responsive Gene Database...... (ERGDB) and were analyzed from multiple aspects. We explored the possible transcription regulation mechanism by capturing highly conserved promoter motifs across orthologous genes, using promoter regions that cover the range of [-1200, +500] relative to the transcription start sites. The motif detection...... is based on ab initio discovery of common cis-elements from the orthologous gene cluster from human, mouse and rat, thus reflecting a degree of promoter sequence preservation during evolution. The identified motifs are linked to transcription factor binding sites based on the TRANSFAC database. In addition...

  12. The Role and Use of Estrogens Following Trauma.

    Science.gov (United States)

    Weniger, Maximilian; Angele, Martin K; Chaudry, Irshad H

    2016-09-01

    Several lines of evidence indicate that female sex is a protective factor in trauma and hemorrhage. In both clinical and experimental studies, proestrus females have been shown to have better chances of survival and reduced rates of posttraumatic sepsis. Estrogen receptors are expressed in a variety of tissues and exert genomic, as well as nongenomic effects. By improving cardiac, pulmonary, hepatic, and immune function, estrogens have been shown to prolong survival in animal models of hemorrhagic shock. Despite encouraging results from experimental studies, retrospective clinical studies have not clearly pointed to advantages of estrogens following trauma-hemorrhage, which may be due to insufficient study design. Therefore, this review aims to give an overview on the current evidence and emphasizes on the importance of further clinical investigation on estrogens following trauma.

  13. Investigating the Regulation of Estrogen Receptor-Mediated Transcription

    National Research Council Canada - National Science Library

    Thackray, Varykina

    2002-01-01

    ...-mediated regulation of specific target genes are still lacking. We have developed an estrogen responsive system in the fruit fly, Drosophila melanogaster in order to explore the functional interactions between ER and other cellular proteins...

  14. Investigating the Regulation of Estrogen Receptor-Mediated Transcription

    National Research Council Canada - National Science Library

    Thackray, Varykina

    2001-01-01

    ...-mediated regulation of specific target genes are still lacking. We have developed an estrogen responsive system in the fruit fly, Drosophila melanogaster in order to explore the functional interactions between ER and other cellular proteins...

  15. A-C Estrogens as Potent and Selective Estrogen Receptor-Beta Agonists (SERBAs) to Enhance Memory Consolidation under Low-Estrogen Conditions.

    Science.gov (United States)

    Hanson, Alicia M; Perera, K L Iresha Sampathi; Kim, Jaekyoon; Pandey, Rajesh K; Sweeney, Noreena; Lu, Xingyun; Imhoff, Andrea; Mackinnon, Alexander Craig; Wargolet, Adam J; Van Hart, Rochelle M; Frick, Karyn M; Donaldson, William A; Sem, Daniel S

    2018-06-04

    Estrogen receptor-beta (ERβ) is a drug target for memory consolidation in postmenopausal women. Herein is reported a series of potent and selective ERβ agonists (SERBAs) with in vivo efficacy that are A-C estrogens, lacking the B and D estrogen rings. The most potent and selective A-C estrogen is selective for activating ER relative to seven other nuclear hormone receptors, with a surprising 750-fold selectivity for the β over α isoform and with EC 50 s of 20-30 nM in cell-based and direct binding assays. Comparison of potency in different assays suggests that the ER isoform selectivity is related to the compound's ability to drive the productive conformational change needed to activate transcription. The compound also shows in vivo efficacy after microinfusion into the dorsal hippocampus and after intraperitoneal injection (0.5 mg/kg) or oral gavage (0.5 mg/kg). This simple yet novel A-C estrogen is selective, brain penetrant, and facilitates memory consolidation.

  16. In Utero Estrogen Exposure Increases Antiestrogen Resistance by Inducing EMT

    Science.gov (United States)

    2015-02-01

    currently unclear. Our recent preclinical study found that maternal exposure to excess estrogens during pregnancy increases the risk that AE resistance in...References: 1. Hilakivi-Clarke L, Clarke R, Onojafe I, Raygada M, Cho E, Lippman M. A maternal diet high in n-6-polyunsaturated fats alters mammary...the rate of obesity in this country (high fat diets resulting in elevated circulating estrogen levels), the prevelance of bisphenol A in our drinking

  17. Caffeine As An Indicator Of Estrogenic Activity In Source Water.

    OpenAIRE

    Montagner, C C; Umbuzeiro, G A; Pasquini, C; Jardim, W F

    2015-01-01

    Caffeine has already been used as an indicator of anthropogenic impacts, especially the ones related to the disposal of sewage in water bodies. In this work, the presence of caffeine has been correlated with the estrogenic activity of water samples measured using the BLYES assay. After testing 96 surface water samples, it was concluded that caffeine can be used to prioritize samples to be tested for estrogenic activity in water quality programs evaluating emerging contaminants with endocrine ...

  18. Caffeine as an indicator of estrogenic activity in source water.

    Science.gov (United States)

    Montagner, C C; Umbuzeiro, G A; Pasquini, C; Jardim, W F

    2014-08-01

    Caffeine has already been used as an indicator of anthropogenic impacts, especially the ones related to the disposal of sewage in water bodies. In this work, the presence of caffeine has been correlated with the estrogenic activity of water samples measured using the BLYES assay. After testing 96 surface water samples, it was concluded that caffeine can be used to prioritize samples to be tested for estrogenic activity in water quality programs evaluating emerging contaminants with endocrine disruptor activity.

  19. Regional differences in the prostate of the neonatally estrogenized mouse

    International Nuclear Information System (INIS)

    Pylkkaenen, L.S.; Santti, R.; Newbold, R.; McLachlan, J.A.

    1991-01-01

    Neonatal estrogenization of the mouse with diethylstilbestrol resulted in time-of-exposure and dose-dependent inhibition of the growth of the prostatic lobes observed at the age of 2 mon. The critical time was the days 1-6 of postnatal life. In neonatally estrogenized (neoDES) mice, responses to 5 alpha-dihydrotestosterone in terms of nuclear 3H-thymidine labelling were altered concomitantly with the inhibition of growth and were in accordance with changes in the relative volumes of epithelium, glandular lumina, and interacinar stroma. Secondary estrogen treatment of neoDES mice with 17 beta-estradiol did not increase 3H-thymidine labelling in the prostate of control or neoDES mice. However, it induced squamous epithelial metaplasia in periurethral collecting ducts and proximal parts of coagulating glands of neoDES animals. In control mice only slight epithelial hyperplasia could be observed after similar treatment. Estrogen receptors, located immunocytochemically in nuclei of stromal cell, corresponded with the sites of increased estrogen sensitivity, observed as metaplastic transformation. When the neoDES animals aged, epithelial hyperplasia and dysplasia could be observed at distinct prostatic sites, ie, the periurethral collecting ducts and the coagulating glands and periurethral glands, and stromal inflammation become more extensive. Almost identical location of the epithelial changes and the altered estrogen response is suggestive of causal relationship

  20. Gender, Estrogen, and Obliterative Lesions in the Lung

    Directory of Open Access Journals (Sweden)

    Hamza Assaggaf

    2017-01-01

    Full Text Available Gender has been shown to impact the prevalence of several lung diseases such as cancer, asthma, chronic obstructive pulmonary disease, and pulmonary arterial hypertension (PAH. Controversy over the protective effects of estrogen on the cardiopulmonary system should be of no surprise as clinical trials of hormone replacement therapy have failed to show benefits observed in experimental models. Potential confounders to explain these inconsistent estrogenic effects include the dose, cellular context, and systemic versus local tissue levels of estrogen. Idiopathic PAH is disproportionately found to be up to 4 times more common in females than in males; however, estrogen levels cannot explain why males develop PAH sooner and have poorer survival. Since the sex steroid hormone 17β-estradiol is a mitogen, obliterative processes in the lung such as cell proliferation and migration may impact the growth of pulmonary tissue or vascular cells. We have reviewed evidence for biological differences of sex-specific lung obliterative lesions and highlighted cell context-specific effects of estrogen in the formation of vessel lumen-obliterating lesions. Based on this information, we provide a biological-based mechanism to explain the sex difference in PAH severity as well as propose a mechanism for the formation of obliterative vascular lesions by estrogens.

  1. Selective estrogen receptor modulators and risk for coronary heart disease.

    Science.gov (United States)

    Cano, A; Hermenegildo, C; Oviedo, P; Tarín, J J

    2007-04-01

    Coronary heart disease (CHD) is the leading cause of death in women in most countries. Atherosclerosis is the main biological process determining CHD. Clinical data support the notion that CHD is sensitive to estrogens, but debate exists concerning the effects of the hormone on atherosclerosis and its complications. Selective estrogen receptor modulators (SERMs) are compounds capable of binding the estrogen receptor to induce a functional profile distinct from estrogens. The possibility that SERMs may shift the estrogenic balance on cardiovascular risk towards a more beneficial profile has generated interest in recent years. There is considerable information on the effects of SERMs on distinct areas that are crucial in atherogenesis. The complexity derived from the diversity of variables affecting their mechanism of action plus the differences between compounds make it difficult to delineate one uniform trend for SERMs. The present picture, nonetheless, is one where SERMs seem less powerful than estrogens in atherosclerosis protection, but more gentle with advanced forms of the disease. The recent publication of the Raloxifene Use for The Heart (RUTH) study has confirmed a neutral effect for raloxifene. Prothrombotic states may favor occlusive thrombi at sites occupied by atheromatous plaques. Platelet activation has received attention as an important determinant of arterial thrombogenesis. Although still sparse, available evidence globally suggests neutral or beneficial effects for SERMs.

  2. Transcriptional targets shared by estrogen receptor- related receptors (ERRs) and estrogen receptor (ER) alpha, but not by ERbeta.

    Science.gov (United States)

    Vanacker, J M; Pettersson, K; Gustafsson, J A; Laudet, V

    1999-01-01

    The physiological activities of estrogens are thought to be mediated by specific nuclear receptors, ERalpha and ERbeta. However, certain tissues, such as the bone, that are highly responsive to estrogens only express a low level of these receptors. Starting from this apparent contradiction, we have evaluated the potentials of two related receptors ERRalpha and ERRbeta to intervene in estrogen signaling. ERalpha, ERRalpha and ERRbeta bind to and activate transcription through both the classical estrogen response element (ERE) and the SF-1 response element (SFRE). In contrast, ERbeta DNA-binding and transcriptional activity is restricted to the ERE. Accordingly, the osteopontin gene promoter is stimulated through SFRE sequences, by ERRalpha as well as by ERalpha, but not by ERbeta. Analysis of the cross-talk within the ER/ERR subgroup of nuclear receptors thus revealed common targets but also functional differences between the two ERs. PMID:10428965

  3. Analysis of 3D models of octopus estrogen receptor with estradiol: evidence for steric clashes that prevent estrogen binding.

    Science.gov (United States)

    Baker, Michael E; Chandsawangbhuwana, Charlie

    2007-09-28

    Relatives of the vertebrate estrogen receptor (ER) are found in Aplysia californica, Octopus vulgaris, Thais clavigera, and Marisa cornuarietis. Unlike vertebrate ERs, invertebrate ERs are constitutively active and do not bind estradiol. To investigate the molecular basis of the absence of estrogen binding, we constructed a 3D model of the putative steroid-binding domain on octopus ER. Our 3D model indicates that binding of estradiol to octopus ER is prevented by steric clashes between estradiol and amino acids in the steroid-binding pocket. In this respect, octopus ER resembles vertebrate estrogen-related receptors (ERR), which have a ligand-binding pocket that cannot accommodate estradiol. Like ERR, octopus ER also may have the activation function 2 domain (AF2) in a configuration that can bind to coactivators in the absence of estrogens, which would explain constitutive activity of octopus ER.

  4. Estrogen-mediated hemangioma-derived stem cells through estrogen receptor-α for infantile hemangioma

    Directory of Open Access Journals (Sweden)

    Zhang L

    2017-07-01

    Full Text Available Ling Zhang,1 Hai Wei Wu,1 Weien Yuan,2 Jia Wei Zheng1 1Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Background: Infantile hemangiomas (IHs are the most common benign vascular tumor of infancy. They occur more frequently in female infants. The cause of hemangioma is currently unknown; however, current studies suggested the importance of estrogen (E2 signaling in hemangioma proliferation. Methods: Hemangioma-derived stem cells (HemSCs were cultured with estrogen for 48–72 h; the cell viability and proliferation were evaluated with the messenger RNA (mRNA and protein expression levels of fibroblast growth factor 2 (FGF2, vascular endothelial growth factor-A (VEGF-A and estrogen receptor-α (ER-α, by application of several in vitro assays, such as methyl thiazolyl tetrazolium (MTT, reverse transcriptase–polymerase chain reaction (RT-PCR, real-time PCR, enzyme-linked immunosorbent assay (ELISA and Western blotting. Also, the cell population’s response to external estrogen was investigated by in vivo experiments. HemSCs and human umbilical vein endothelial cells (HUVECs were mixed and injected subcutaneously into 20 flank of BALB/c-nu mice, which were randomly divided into 5 groups based on different E2 treatment doses (0, 0.01, 0.1 and 1 mg, respectively, 0.1 mg dimethyl sulfoxide (DMSO as control. Each group of mice were treated intramuscularly every week, then 2 and 4 weeks later, the subcutaneous implants were harvested and evaluated the tumor tissues with microvessel density (MVD assay and immunohistochemistry. Results: The study demonstrated that application of E2 increased the expression of FGF2, VEGF-A, and ER-α in HemSCs with the optimal concentration from 10−9 to 10−5 M. Two

  5. Effects of gamma irradiation on the DNA-protein complex between the estrogen response element and the estrogen receptor

    Czech Academy of Sciences Publication Activity Database

    Štísová, Viktorie; Goffinont, S.; Maurizot, M. S.; Davídková, Marie

    2010-01-01

    Roč. 79, č. 8 (2010), s. 880-889 ISSN 0969-806X R&D Projects: GA MŠk 1P05OC085; GA MŠk OC09012 Institutional research plan: CEZ:AV0Z10480505 Keywords : DNA-protein complex * estrogen response element * estrogen receptor * ionizing radiation Subject RIV: BO - Biophysics Impact factor: 1.132, year: 2010

  6. Retinoid X receptor and peroxisome proliferator-activated receptor activate an estrogen responsive gene independent of the estrogen receptor.

    Science.gov (United States)

    Nuñez, S B; Medin, J A; Braissant, O; Kemp, L; Wahli, W; Ozato, K; Segars, J H

    1997-03-14

    Estrogen receptors regulate transcription of genes essential for sexual development and reproductive function. Since the retinoid X receptor (RXR) is able to modulate estrogen responsive genes and both 9-cis RA and fatty acids influenced development of estrogen responsive tumors, we hypothesized that estrogen responsive genes might be modulated by RXR and the fatty acid receptor (peroxisome proliferator-activated receptor, PPAR). To test this hypothesis, transfection assays in CV-1 cells were performed with an estrogen response element (ERE) coupled to a luciferase reporter construct. Addition of expression vectors for RXR and PPAR resulted in an 11-fold increase in luciferase activity in the presence of 9-cis RA. Furthermore, mobility shift assays demonstrated binding of RXR and PPAR to the vitellogenin A2-ERE and an ERE in the oxytocin promoter. Methylation interference assays demonstrated that specific guanine residues required for RXR/PPAR binding to the ERE were similar to residues required for ER binding. Moreover, RXR domain-deleted constructs in transfection assays showed that activation required RXR since an RXR delta AF-2 mutant completely abrogated reporter activity. Oligoprecipitation binding studies with biotinylated ERE and (35)S-labeled in vitro translated RXR constructs confirmed binding of delta AF-2 RXR mutant to the ERE in the presence of baculovirus-expressed PPAR. Finally, in situ hybridization confirmed RXR and PPAR mRNA expression in estrogen responsive tissues. Collectively, these data suggest that RXR and PPAR are present in reproductive tissues, are capable of activating estrogen responsive genes and suggest that the mechanism of activation may involve direct binding of the receptors to estrogen response elements.

  7. Estrogenic and anti-estrogenic influences in cultured brown trout hepatocytes: Focus on the expression of some estrogen and peroxisomal related genes and linked phenotypic anchors.

    Science.gov (United States)

    Madureira, Tânia Vieira; Malhão, Fernanda; Pinheiro, Ivone; Lopes, Célia; Ferreira, Nádia; Urbatzka, Ralph; Castro, L Filipe C; Rocha, Eduardo

    2015-12-01

    Estrogens, estrogenic mimics and anti-estrogenic compounds are known to target estrogen receptors (ER) that can modulate other nuclear receptor signaling pathways, such as those controlled by the peroxisome proliferator-activated receptor (PPAR), and alter organelle (inc. peroxisome) morphodynamics. By using primary isolated brown trout (Salmo trutta f. fario) hepatocytes after 72 and 96h of exposure we evaluated some effects in selected molecular targets and in peroxisomal morphological features caused by: (1) an ER agonist (ethinylestradiol-EE2) at 1, 10 and 50μM; (2) an ER antagonist (ICI 182,780) at 10 and 50μM; and (3) mixtures of both (Mix I-10μM EE2 and 50μM ICI; Mix II-1μM EE2 and 10μM ICI and Mix III-1μM EE2 and 50μM ICI). The mRNA levels of the estrogenic targets (ERα, ERβ-1 and vitellogenin A-VtgA) and the peroxisome structure/function related genes (catalase, urate oxidase-Uox, 17β-hydroxysteroid dehydrogenase 4-17β-HSD4, peroxin 11α-Pex11α and PPARα) were analyzed by real-time polymerase chain reaction (RT-PCR). Stereology combined with catalase immunofluorescence revealed a significant reduction in peroxisome volume densities at 50μM of EE2 exposure. Concomitantly, at the same concentration, electron microscopy showed smaller peroxisome profiles, exacerbated proliferation of rough endoplasmic reticulum, and a generalized cytoplasmic vacuolization of hepatocytes. Catalase and Uox mRNA levels decreased in all estrogenic stimuli conditions. VtgA and ERα mRNA increased after all EE2 treatments, while ERβ-1 had an inverse pattern. The EE2 action was reversed by ICI 182,780 in a concentration-dependent manner, for VtgA, ERα and Uox. Overall, our data show the great value of primary brown trout hepatocytes to study the effects of estrogenic/anti-estrogenic inputs in peroxisome kinetics and in ER and PPARα signaling, backing the still open hypothesis of crosstalk interactions between these pathways and calling for more mechanistic

  8. No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals.

    Science.gov (United States)

    Bannister, Richard; Beresford, Nicola; Granger, David W; Pounds, Nadine A; Rand-Weaver, Mariann; White, Roger; Jobling, Susan; Routledge, Edwin J

    2013-09-15

    Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro. We investigated the effects of estradiol-17β and 4-tert-Octylphenol exposure on in vivo estrogen receptor (ER) and estrogen-related receptor (ERR) gene transcription in the reproductive and neural tissues of the gastropod snail M. cornuarietis over a 12-week period. There was no significant effect (p>0.05) of treatment on gene transcription levels between exposed and non-exposed snails. Absence of a direct interaction of estradiol-17β and 4-tert-Octylphenol with mollusc ER and ERR protein was also supported by in vitro studies in transfected HEK-293 cells. Additional in vitro studies with a selection of other potential ligands (including methyl-testosterone, 17α-ethinylestradiol, 4-hydroxytamoxifen, diethylstilbestrol, cyproterone acetate and ICI182780) showed no interaction when tested using this assay. In repeated in vitro tests, however, genistein (with mcER-like) and bisphenol-A (with mcERR) increased reporter gene expression at high concentrations only (>10(-6)M for Gen and >10(-5)M for BPA, respectively). Like vertebrate estrogen receptors, the mollusc ER protein bound to the consensus vertebrate estrogen-response element (ERE). Together, these data provide no substantial evidence that mcER-like and mcERR activation and transcript levels in tissues are modulated by the vertebrate estrogen estradiol-17β or 4-tert-Octylphenol in vivo, or that other ligands of vertebrate ERs and ERRs (with the possible exception of genistein and

  9. No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals☆☆☆

    Science.gov (United States)

    Bannister, Richard; Beresford, Nicola; Granger, David W.; Pounds, Nadine A.; Rand-Weaver, Mariann; White, Roger; Jobling, Susan; Routledge, Edwin J.

    2013-01-01

    Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro. We investigated the effects of estradiol-17β and 4-tert-Octylphenol exposure on in vivo estrogen receptor (ER) and estrogen-related receptor (ERR) gene transcription in the reproductive and neural tissues of the gastropod snail M. cornuarietis over a 12-week period. There was no significant effect (p > 0.05) of treatment on gene transcription levels between exposed and non-exposed snails. Absence of a direct interaction of estradiol-17β and 4-tert-Octylphenol with mollusc ER and ERR protein was also supported by in vitro studies in transfected HEK-293 cells. Additional in vitro studies with a selection of other potential ligands (including methyl-testosterone, 17α-ethinylestradiol, 4-hydroxytamoxifen, diethylstilbestrol, cyproterone acetate and ICI182780) showed no interaction when tested using this assay. In repeated in vitro tests, however, genistein (with mcER-like) and bisphenol-A (with mcERR) increased reporter gene expression at high concentrations only (>10−6 M for Gen and >10−5 M for BPA, respectively). Like vertebrate estrogen receptors, the mollusc ER protein bound to the consensus vertebrate estrogen-response element (ERE). Together, these data provide no substantial evidence that mcER-like and mcERR activation and transcript levels in tissues are modulated by the vertebrate estrogen estradiol-17β or 4-tert-Octylphenol in vivo, or that other ligands of vertebrate ERs and ERRs (with the possible exception of

  10. Effects of gamma irradiation on the DNA-protein complex between the estrogen response element and the estrogen receptor

    Energy Technology Data Exchange (ETDEWEB)

    Stisova, Viktorie [Department of Radiation Dosimetry, Nuclear Physics Institute AS CR, Na Truhlarce 39/64, 18086 Praha 8 (Czech Republic); Goffinont, Stephane; Spotheim-Maurizot, Melanie [Centre de Biophysique Moleculaire CNRS, rue Charles Sadron, 45071 Orleans Cedex 2 (France); Davidkova, Marie, E-mail: davidkova@ujf.cas.c [Department of Radiation Dosimetry, Nuclear Physics Institute AS CR, Na Truhlarce 39/64, 18086 Praha 8 (Czech Republic)

    2010-08-15

    Signaling by estrogens, risk factors in breast cancer, is mediated through their binding to the estrogen receptor protein (ER), followed by the formation of a complex between ER and a DNA sequence, called estrogen response element (ERE). Anti-estrogens act as competitive inhibitors by blocking the signal transduction. We have studied in vitro the radiosensitivity of the complex between ERalpha, a subtype of this receptor, and a DNA fragment bearing ERE, as well as the influence of an estrogen (estradiol) or an anti-estrogen (tamoxifen) on this radiosensitivity. We observe that the complex is destabilized upon irradiation with gamma rays in aerated aqueous solution. The analysis of the decrease of binding abilities of the two partners shows that destabilization is mainly due to the damage to the protein. The destabilization is reduced when irradiating in presence of tamoxifen and is increased in presence of estradiol. These effects are due to opposite influences of the ligands on the loss of binding ability of ER. The mechanism that can account for our results is: binding of estradiol or tamoxifen induces distinct structural changes of the ER ligand-binding domain that can trigger (by allostery) distinct structural changes of the ER DNA-binding domains and thus, can differently affect ER-ERE interaction.

  11. Estrogenic and anti-estrogenic influences in cultured brown trout hepatocytes: Focus on the expression of some estrogen and peroxisomal related genes and linked phenotypic anchors

    International Nuclear Information System (INIS)

    Madureira, Tânia Vieira; Malhão, Fernanda; Pinheiro, Ivone; Lopes, Célia; Ferreira, Nádia; Urbatzka, Ralph; Castro, L. Filipe C.; Rocha, Eduardo

    2015-01-01

    Highlights: • Evidence of crosstalk between estrogens and peroxisomal pathways in brown trout. • VtgA and ERα mRNA levels increased after 1, 10 and 50 μM of ethinylestradiol (EE2). • ERβ-1, catalase and urate oxidase mRNA levels decreased after estrogenic stimuli. • Estrogenic effects in VtgA, ERα and Uox mRNA levels were reverted by ICI 182,780. • Immunofluorescence/electron microscopy shows smaller peroxisomes after 50 μM of EE2. - Abstract: Estrogens, estrogenic mimics and anti-estrogenic compounds are known to target estrogen receptors (ER) that can modulate other nuclear receptor signaling pathways, such as those controlled by the peroxisome proliferator-activated receptor (PPAR), and alter organelle (inc. peroxisome) morphodynamics. By using primary isolated brown trout (Salmo trutta f. fario) hepatocytes after 72 and 96 h of exposure we evaluated some effects in selected molecular targets and in peroxisomal morphological features caused by: (1) an ER agonist (ethinylestradiol—EE2) at 1, 10 and 50 μM; (2) an ER antagonist (ICI 182,780) at 10 and 50 μM; and (3) mixtures of both (Mix I—10 μM EE2 and 50 μM ICI; Mix II—1 μM EE2 and 10 μM ICI and Mix III—1 μM EE2 and 50 μM ICI). The mRNA levels of the estrogenic targets (ERα, ERβ-1 and vitellogenin A—VtgA) and the peroxisome structure/function related genes (catalase, urate oxidase—Uox, 17β-hydroxysteroid dehydrogenase 4—17β-HSD4, peroxin 11α—Pex11α and PPARα) were analyzed by real-time polymerase chain reaction (RT-PCR). Stereology combined with catalase immunofluorescence revealed a significant reduction in peroxisome volume densities at 50 μM of EE2 exposure. Concomitantly, at the same concentration, electron microscopy showed smaller peroxisome profiles, exacerbated proliferation of rough endoplasmic reticulum, and a generalized cytoplasmic vacuolization of hepatocytes. Catalase and Uox mRNA levels decreased in all estrogenic stimuli conditions. VtgA and ERα m

  12. Estrogenic and anti-estrogenic influences in cultured brown trout hepatocytes: Focus on the expression of some estrogen and peroxisomal related genes and linked phenotypic anchors

    Energy Technology Data Exchange (ETDEWEB)

    Madureira, Tânia Vieira, E-mail: tvmadureira@icbas.up.pt [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Institute of Biomedical Sciences Abel Salazar, U.Porto (ICBAS)—University of Porto, Laboratory of Histology and Embryology, Department of Microscopy, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto (Portugal); Malhão, Fernanda; Pinheiro, Ivone; Lopes, Célia; Ferreira, Nádia [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Institute of Biomedical Sciences Abel Salazar, U.Porto (ICBAS)—University of Porto, Laboratory of Histology and Embryology, Department of Microscopy, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto (Portugal); Urbatzka, Ralph [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Castro, L. Filipe C. [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Faculty of Sciences (FCUP), U.Porto—University of Porto, Department of Biology, Rua do Campo Alegre, P 4169-007 Porto (Portugal); Rocha, Eduardo [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Institute of Biomedical Sciences Abel Salazar, U.Porto (ICBAS)—University of Porto, Laboratory of Histology and Embryology, Department of Microscopy, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto (Portugal)

    2015-12-15

    Highlights: • Evidence of crosstalk between estrogens and peroxisomal pathways in brown trout. • VtgA and ERα mRNA levels increased after 1, 10 and 50 μM of ethinylestradiol (EE2). • ERβ-1, catalase and urate oxidase mRNA levels decreased after estrogenic stimuli. • Estrogenic effects in VtgA, ERα and Uox mRNA levels were reverted by ICI 182,780. • Immunofluorescence/electron microscopy shows smaller peroxisomes after 50 μM of EE2. - Abstract: Estrogens, estrogenic mimics and anti-estrogenic compounds are known to target estrogen receptors (ER) that can modulate other nuclear receptor signaling pathways, such as those controlled by the peroxisome proliferator-activated receptor (PPAR), and alter organelle (inc. peroxisome) morphodynamics. By using primary isolated brown trout (Salmo trutta f. fario) hepatocytes after 72 and 96 h of exposure we evaluated some effects in selected molecular targets and in peroxisomal morphological features caused by: (1) an ER agonist (ethinylestradiol—EE2) at 1, 10 and 50 μM; (2) an ER antagonist (ICI 182,780) at 10 and 50 μM; and (3) mixtures of both (Mix I—10 μM EE2 and 50 μM ICI; Mix II—1 μM EE2 and 10 μM ICI and Mix III—1 μM EE2 and 50 μM ICI). The mRNA levels of the estrogenic targets (ERα, ERβ-1 and vitellogenin A—VtgA) and the peroxisome structure/function related genes (catalase, urate oxidase—Uox, 17β-hydroxysteroid dehydrogenase 4—17β-HSD4, peroxin 11α—Pex11α and PPARα) were analyzed by real-time polymerase chain reaction (RT-PCR). Stereology combined with catalase immunofluorescence revealed a significant reduction in peroxisome volume densities at 50 μM of EE2 exposure. Concomitantly, at the same concentration, electron microscopy showed smaller peroxisome profiles, exacerbated proliferation of rough endoplasmic reticulum, and a generalized cytoplasmic vacuolization of hepatocytes. Catalase and Uox mRNA levels decreased in all estrogenic stimuli conditions. VtgA and ERα m

  13. A Non-Nuclear Role of the Estrogen Receptor Alpha in the Regulation of Cell-Cell Interactions

    National Research Council Canada - National Science Library

    Darimont, Beatrice D

    2006-01-01

    .... The actions of estrogens are mediated by the estrogen receptors ERalpha and ERbeta. These hormone-regulated transcription factors translate the presence of estrogen into changes in gene expression...

  14. Postmenopausal vaginal atrophy: evaluation of treatment with local estrogen therapy

    Directory of Open Access Journals (Sweden)

    Minkin MJ

    2014-03-01

    Full Text Available Mary Jane Minkin,1 Ricardo Maamari,2 Suzanne Reiter3 1Department of Gynecology and Reproductive Medicine, Yale University School of Medicine, New Haven, CT, USA; 2Novo Nordisk Inc., Plainsboro, NJ, USA; 3Mid-County Health Center, Largo, FL, USA Abstract: Postmenopausal vaginal atrophy, resulting from decreased estrogen production, frequently requires treatment. Estrogen preparations provide the most effective treatment; local application is preferred to systemic drugs when treating only vaginal symptoms. As local estrogen therapies have comparable efficacy, this study aimed to understand treatment practices, assess experiences with different forms of local estrogen-delivering applicators, and evaluate satisfaction. Women who were US residents aged ≥18 years, menopausal (no spontaneous menstrual period for ≥1 year or with a double oophorectomy, and receiving local estrogen therapy for 1–6 months (vaginal cream [supplied with a reusable applicator] or vaginal tablets [supplied with a single-use/disposable applicator], completed an online questionnaire. Data from 200 women (100 cream users and 100 tablet users; mean therapy duration 3.48 months showed that most stored medication in the room in which it was applied (88% and applied it at bedtime (71%, a procedure for which cream users required, on average, more than twice the time of tablet users (5.08 minutes versus 2.48 minutes. Many cream users applied larger-than-prescribed amounts of cream, attempting to achieve greater efficacy (42%, or lower-than-recommended doses (45%, most frequently to avoid messiness (33% or leakage (30%. More tablet users (69% than cream users (14% were "extremely satisfied" with their applicator. Postmenopausal women using local estrogen therapy were generally more satisfied with the application of vaginal tablets than cream. Patient satisfaction may help to facilitate accurate dosing. Positive perceptions of medication will help to optimize treatment, which

  15. THE ESTROGENS / CHROMIUM INTERACTION IN THE NITRIC OXIDE GENERATION.

    Science.gov (United States)

    Sawicka, Ewa; Piwowar, Agnieszka; Musiala, Tomasz; Dlugosz, Anna

    2017-05-01

    The interaction of estrogens with environmental toxins in free radicals generation: reactive oxygen species (ROS) or reactive nitrogen species (RNS) which participates in cancerogenesis is not yet recognized. Chromium(VI) is widely present in environment. One of its toxicity pathway is free radicals generation. Estrogens have the ability to scavenge free radicals, but may also act as prooxidants. Both chromium(VI) and estrogens are classified by International Agency for Research on Cancer (IARC) as carcinogens, so synergistic effect seems very dangerous. The interaction of chromium and estrogens in ROS generation are partly described but there are no reports on estrogen/chromium interaction on nitric oxide (NO) generation. The aim of the study was to examine the interaction of chromium(VI) and 17-p-estradiol (E2) on NO level in human blood as well as the role of E2 metabolites: 4-hydroxyestradiol (4-OHE2) and 16a-hydroxyestrone (16α-OHE1) in these processes. The NO level was estimated with the diagnostic kit (Nitric Oxide Colorimetric Detection Kit from Arbor Assays) in human blood in vitm. The results showed that Cr(VI) in used concentration (0.5; 1.0 and 5.0 gg/mL) decreases significantly NO level in blood, acting antagonistically to E2 and 4-OHE2. Estrogens (E2, 4-OHE2 and 16α-OHEI) do not protect against inhibiting effect of Cr(VI) on nitric oxide generation in blood because after combined exposure the decreased production of NO in blood was noted. In conclusion, presented results provide the information about the character of estrogen/Cr(VI) interaction in NO level in human blood. It is important knowledge for cardio protected effect e.g., hormone replacement therapy in environmental or occupational exposure to Cr(VI), chromium supplementation, also important for cancer risk evaluation.

  16. Targeted basic research to highlight the role of estrogen and estrogen receptors in the cardiovascular system.

    Science.gov (United States)

    Dworatzek, Elke; Mahmoodzadeh, Shokoufeh

    2017-05-01

    Epidemiological, clinical and animal studies revealed that sex differences exist in the manifestation and outcome of cardiovascular disease (CVD). The underlying molecular mechanisms implicated in these sex differences are not fully understood. The reasons for sex differences in CVD are definitely multifactorial, but major evidence points to the contribution of sex steroid hormone, 17β-estradiol (E2), and its receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). In this review, we summarize past and present studies that implicate E2 and ER as important determinants of sexual dimorphism in the physiology and pathophysiology of the heart. In particular, we give an overview of studies aimed to reveal the role of E2 and ER in the physiology of the observed sex differences in CVD using ER knock-out mice. Finally, we discuss recent findings from novel transgenic mouse models, which have provided new information on the sexual dimorphic roles of ER specifically in cardiomyocytes under pathological conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Designer interface peptide grafts target estrogen receptor alpha dimerization

    International Nuclear Information System (INIS)

    Chakraborty, S.; Asare, B.K.; Biswas, P.K.; Rajnarayanan, R.V.

    2016-01-01

    The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

  18. Designer interface peptide grafts target estrogen receptor alpha dimerization

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, S. [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Asare, B.K. [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States); Biswas, P.K., E-mail: pbiswas@tougaloo.edu [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Rajnarayanan, R.V., E-mail: rajendra@buffalo.edu [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States)

    2016-09-09

    The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

  19. Immunohistochemical Expression of Estrogen and Progesterone Receptors in Epulis Fissuratum

    Directory of Open Access Journals (Sweden)

    Maryam Seyedmajidi

    2013-01-01

    Full Text Available Background: Epulis Fissuratum (Epulis Fissuratum (EF or Denture Epulis or inflammatory fibrous hyperplasia is a common hyperplastic tumor-like lesion with reactive nature, related to loose and ill-fitting, full or partial removable dentures and it is more common in women than men. For this reason, hormonal influences may also play role in its creation. The effect of steroid hormones especially sex hormones (Estrogen and progesterone on oral mucosa is identified in some studies. In the present study, the distribution pattern and presence of estrogen and progesterone receptors in epithelial, stromal, endothelial and inflammatory cells in Epulis Fissuratum was investigated. Materials and Methods: This cross-sectional study was carried out on 30 samples of paraffin blocks with Epulis Fissuratum diagnosis and 30 samples of normal mucosal tissues as a control group who have had surgery as a margin beside the above lesions and had been obtained from the oral and maxillofacial pathology departement of Babol Dental School since 2003 up to 2010. Intensity of staining and immunoreactivity were evaluated using subjective index and considering the positive control group (breast carcinoma.Results: Epithelial, stromal, endothelial and inflammatory cells didn’t show reaction with monoclonal antibodies against estrogen and progesterone in none of the samples. Conclusion: It seems that the hypothesis of the existence of estrogen and progesterone receptors in epulis fissuratum and normal oral mucosa is ruled out. The possibility of direct effect of estrogen and progesterone in occurring of epulis fissuratum is rejected.

  20. Multi-year prediction of estrogenicity in municipal wastewater effluents.

    Science.gov (United States)

    Arlos, Maricor J; Parker, Wayne J; Bicudo, José R; Law, Pam; Marjan, Patricija; Andrews, Susan A; Servos, Mark R

    2018-01-01

    In this study, the estrogenicity of two major wastewater treatment plant (WWTP) effluents located in the central reaches of the Grand River watershed in southern Ontario was estimated using population demographics, excretion rates, and treatment plant-specific removals. Due to the lack of data on estrogen concentrations from direct measurements at WWTPs, the treatment efficiencies through the plants were estimated using the information obtained from an effects-directed analysis. The results show that this approach could effectively estimate the estrogenicity of WWTP effluents, both before and after major infrastructure upgrades were made at the Kitchener WWTP. The model was then applied to several possible future scenarios including population growth and river low flow conditions. The scenario analyses showed that post-upgrade operation of the Kitchener WWTP will not release highly estrogenic effluent under the 2041 projected population increase (36%) or summer low flows. Similarly, the Waterloo WWTP treatment operation is also expected to improve once the upgrades have been fully implemented and is expected to effectively treat estrogens even under extreme scenarios of population growth and river flows. The developed model may be employed to support decision making on wastewater management strategies designed for environmental protection, especially on reducing the endocrine effects in fish exposed to WWTP effluents. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. A novel estrogen-regulated avian apolipoprotein☆

    Science.gov (United States)

    Nikolay, Birgit; Plieschnig, Julia A.; Šubik, Desiree; Schneider, Jeannine D.; Schneider, Wolfgang J.; Hermann, Marcela

    2013-01-01

    In search for yet uncharacterized proteins involved in lipid metabolism of the chicken, we have isolated a hitherto unknown protein from the serum lipoprotein fraction with a buoyant density of ≤1.063 g/ml. Data obtained by protein microsequencing and molecular cloning of cDNA defined a 537 bp cDNA encoding a precursor molecule of 178 residues. As determined by SDS-PAGE, the major circulating form of the protein, which we designate apolipoprotein-VLDL-IV (Apo-IV), has an apparent Mr of approximately 17 kDa. Northern Blot analysis of different tissues of laying hens revealed Apo-IV expression mainly in the liver and small intestine, compatible with an involvement of the protein in lipoprotein metabolism. To further investigate the biology of Apo-IV, we raised an antibody against a GST-Apo-IV fusion protein, which allowed the detection of the 17-kDa protein in rooster plasma, whereas in laying hens it was detectable only in the isolated ≤1.063 g/ml density lipoprotein fraction. Interestingly, estrogen treatment of roosters caused a reduction of Apo-IV in the liver and in the circulation to levels similar to those in mature hens. Furthermore, the antibody crossreacted with a 17-kDa protein in quail plasma, indicating conservation of Apo-IV in avian species. In search for mammalian counterparts of Apo-IV, alignment of the sequence of the novel chicken protein with those of different mammalian apolipoproteins revealed stretches with limited similarity to regions of ApoC-IV and possibly with ApoE from various mammalian species. These data suggest that Apo-IV is a newly identified avian apolipoprotein. PMID:24047540

  2. Higher estrogen levels are not associated with larger hippocampi and better memory performance

    NARCIS (Netherlands)

    T. den Heijer (Tom); M.I. Geerlings (Miriam); F.H. de Jong (Frank); L.J. Launer (Lenore); H.A.P. Pols (Huib); M.M.B. Breteler (Monique); A. Hofman (Albert)

    2003-01-01

    textabstractBACKGROUND: Estrogens may prevent cognitive decline and Alzheimer disease. Animal study findings have shown beneficial effects of estrogen on the brain, particularly on the hippocampus, a structure related to memory performance and early Alzheimer disease. OBJECTIVE:

  3. Estrogen-Modulated Response of Breast Cancer To Vitamin D and Its Analogs: Role of IGF

    National Research Council Canada - National Science Library

    Dolezalova, Hana

    1999-01-01

    ... (LPA) and sphingosine 1-phosphate (S1P). Estrogen receptor positive and estrogen receptor negative cells express predominantly Edg-2 and Edg-4 Rs for LPA and Edg-3 for Sip, which transduce proliferative responses by direct nuclear signaling...

  4. Estrogenic Activity of Perfluoroalkyl Acids in Juvenile Rainbow Trout (Oncorhynchus Mykiss)

    Science.gov (United States)

    The potential estrogenic activity of perfluoroalkyl acids (PFAAs) was determined using separate screening and dose response studies with juvenile rainbow trout (Oncorhynchus mykiss). Results of this study indicate that some PFAAs may act as estrogens in fish.

  5. The Distinct Effects of Estrogen and Hydrostatic Pressure on Mesenchymal Stem Cells Differentiation: Involvement of Estrogen Receptor Signaling.

    Science.gov (United States)

    Zhao, Ying; Yi, Fei-Zhou; Zhao, Yin-Hua; Chen, Yong-Jin; Ma, Heng; Zhang, Min

    2016-10-01

    This study aimed to investigate the differential and synergistic effects of mechanical stimulation and estrogen on the proliferation and osteogenic or chondrogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs) and the roles of estrogen receptor (ER) in them. BMSCs were isolated and cultured using the whole bone marrow adherence method, and flow cytometry was used to identify the surface marker molecules of BMSCs. Cells were pre-treated with 1 nM 17β-estradiol or 1 nM of the estrogen receptor antagonist tamoxifen. Then, the cells were stimulated with hydrostatic pressure. Assessment included flow cytometry analysis of the cell cycle; immunofluorescent staining for F-actin; protein quantification for MAPK protein; and mRNA analysis for Col I, OCN, OPN and BSP after osteogenic induction and Sox-9, Aggrecan and Col-II after chondrogenic induction. Hydrostatic pressure (90 kPa/1 h) and 1 nM 17β-estradiol enhanced the cellular proliferation ability and the cytoskeleton activity but without synergistic biological effects. Estrogen activated ERKs and JNKs simultaneously and promoted the osteogenic differentiation, whereas the pressure just caused JNK-1/2 activation and promoted the chondrogenic differentiation of BMSCs. Estrogen had antagonism effect on chondrogenic promotion of hydrostatic pressure. Mechanobiological effects of hydrostatic pressure are closely associated with ERα activity. MAPK molecules and F-actin were likely to be important mediator molecules in the ER-mediated mechanotransduction of BMSCs.

  6. Estrogen Signaling in Lung Cancer: An Opportunity for Novel Therapy

    International Nuclear Information System (INIS)

    Baik, Christina S.; Eaton, Keith D.

    2012-01-01

    Lung cancer is the leading cause of cancer death in U.S. and represents a major public health burden. Epidemiologic data have suggested that lung cancer in women may possess different biological characteristics compared to men, as evidenced by a higher proportion of never-smokers among women with lung cancer. Emerging data indicate that female hormones such as estrogen and progesterone play a significant role in lung carcinogenesis. It has been reported that estrogen and progesterone receptors are expressed in lung cancer cell lines as well as in patient-derived tumors. Hormone related risk factors such as hormone replacement therapy have been implicated in lung carcinogenesis and several preclinical studies show activity of anti-estrogen therapy in lung cancer. In this review, we summarize the emerging evidence for the role of reproductive hormones in lung cancer and implications for lung cancer therapy

  7. Possible Estrogen Dependency in the Pathogenesis of Branchial Cleft Cysts

    Directory of Open Access Journals (Sweden)

    Jan D. Raguse

    2017-01-01

    Full Text Available Background. Even though branchial cleft cysts are currently accepted as a congenital anomaly, there is often a long delay until clinical presentation; branchial cleft cysts classically appear in the second to fourth decade of life. Our observation of their occurrence in three pregnant women encouraged us to contemplate a possible hormonal influence. Methods. Immunohistological analysis was performed for the evaluation of the estrogen receptor alpha (ERα in paraffin-embedded tissue specimens of 16 patients with a diagnosis of branchial cleft cyst, with three of them being pregnant. Results. Expression of ERα was detected within epithelial cells only in branchial cleft cysts in pregnant females; moreover, higher growth fractions (Ki-67/Mib1 were found. Conclusion. The fact that the estrogen receptor was expressed only in pregnant women, in contrast to 13 investigated cases, may suggest that the high level of estrogen in pregnancy is a possible explanation for the spontaneous growth of branchial cleft cysts.

  8. Possible Estrogen Dependency in the Pathogenesis of Branchial Cleft Cysts.

    Science.gov (United States)

    Raguse, Jan D; Anagnostopoulos, Ioannis; Doll, Christian; Heiland, Max; Jöhrens, Korinna

    2017-01-01

    Even though branchial cleft cysts are currently accepted as a congenital anomaly, there is often a long delay until clinical presentation; branchial cleft cysts classically appear in the second to fourth decade of life. Our observation of their occurrence in three pregnant women encouraged us to contemplate a possible hormonal influence. Immunohistological analysis was performed for the evaluation of the estrogen receptor alpha (ER α ) in paraffin-embedded tissue specimens of 16 patients with a diagnosis of branchial cleft cyst, with three of them being pregnant. Expression of ER α was detected within epithelial cells only in branchial cleft cysts in pregnant females; moreover, higher growth fractions (Ki-67/Mib1) were found. The fact that the estrogen receptor was expressed only in pregnant women, in contrast to 13 investigated cases, may suggest that the high level of estrogen in pregnancy is a possible explanation for the spontaneous growth of branchial cleft cysts.

  9. Role of Estrogen Receptor Signaling in Breast Cancer Metastasis

    International Nuclear Information System (INIS)

    Roy, S.S.; Vadlamudi, R.K.

    2012-01-01

    Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis

  10. Bisphenol A in dental sealants and its estrogen like effect

    Directory of Open Access Journals (Sweden)

    Manu Rathee

    2012-01-01

    Full Text Available Bisphenol A or BPA-based epoxy resins are widely used in the manufacture of commercial products, including dental resins, polycarbonate plastics, and the inner coating of food cans. BPA is a precursor to the resin monomer Bis-GMA. During the manufacturing process of Bis-GMA dental sealants, Bisphenol A (BPA might be present as an impurity or as a degradation product of Bis-DMA through esterases present in saliva. Leaching of these monomers from resins can occur during the initial setting period and in conjunction with fluid sorption and desorption over time and this chemical leach from dental sealants may be bioactive. Researchers found an estrogenic effect with BPA, Bis-DMA, and Bis-GMA because BPA lacks structural specificity as a natural ligand to the estrogen receptor. It generated considerable concern regarding the safety of dental resin materials. This review focuses on the BPA in dental sealants and its estrogen-like effect.

  11. Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer

    OpenAIRE

    Singhal, Hari; Greene, Marianne E.; Tarulli, Gerard; Zarnke, Allison L.; Bourgo, Ryan J.; Laine, Muriel; Chang, Ya-Fang; Ma, Shihong; Dembo, Anna G.; Raj, Ganesh V.; Hickey, Theresa E.; Tilley, Wayne D.; Greene, Geoffrey L.

    2016-01-01

    The functional role of progesterone receptor (PR) and its impact on estrogen signaling in breast cancer remain controversial. In primary ER+ (estrogen receptor?positive)/PR+ human tumors, we report that PR reprograms estrogen signaling as a genomic agonist and a phenotypic antagonist. In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak ...

  12. Estrogens and the risk of complex regional pain syndrome (CRPS).

    Science.gov (United States)

    de Mos, M; Huygen, F J P M; Stricker, B H Ch; Dieleman, J P; Sturkenboom, M C J M

    2009-01-01

    Since complex regional pain syndrome (CRPS) shows a clear female predominance, we investigated the association between the cumulative as well as current exposure to estrogens, and CRPS. A population-based case-control study was conducted in the Integrated Primary Care Information (IPCI) project in the Netherlands. Cases were identified from electronic records (1996-2005) and included if they were confirmed during a visit (using International Association for the Study of Pain Criteria), or had been diagnosed by a specialist. Controls were matched to cases on gender, age, calendar time, and injury. Measures of cumulative endogenous estrogen exposure were obtained by questionnaire and included age of menarche and menopause, menstrual life, and cumulative months of pregnancy and breast-feeding. Current estrogen exposure at CRPS onset was retrieved from the electronic medical records and determined by current pregnancy or by the use of oral contraceptive (OC) drugs or hormonal replacement therapy (HRT). Hundred and forty-three female cases (1493 controls) were included in analyses on drug use and pregnancies, while cumulative endogenous estrogen exposure was studied in 53 cases (58 controls) for whom questionnaire data were available. There was no association between CRPS and either cumulative endogenous estrogen exposure, OC, or HRT use. CRPS onset was increased during the first 6 months after pregnancy (OR: 5.6, 95%CI: 1.0-32.4), although based on small numbers. We did not find an association between CRPS onset and cumulative endogenous estrogen exposure or current OC or HRT use, but more powered studies are needed to exclude potential minor associations.

  13. Estrogen-cholinergic interactions: Implications for cognitive aging.

    Science.gov (United States)

    Newhouse, Paul; Dumas, Julie

    2015-08-01

    This article is part of a Special Issue "Estradiol and Cognition". While many studies in humans have investigated the effects of estrogen and hormone therapy on cognition, potential neurobiological correlates of these effects have been less well studied. An important site of action for estrogen in the brain is the cholinergic system. Several decades of research support the critical role of CNS cholinergic systems in cognition in humans, particularly in learning and memory formation and attention. In humans, the cholinergic system has been implicated in many aspects of cognition including the partitioning of attentional resources, working memory, inhibition of irrelevant information, and improved performance on effort-demanding tasks. Studies support the hypothesis that estradiol helps to maintain aspects of attention and verbal and visual memory. Such cognitive domains are exactly those modulated by cholinergic systems and extensive basic and preclinical work over the past several decades has clearly shown that basal forebrain cholinergic systems are dependent on estradiol support for adequate functioning. This paper will review recent human studies from our laboratories and others that have extended preclinical research examining estrogen-cholinergic interactions to humans. Studies examined include estradiol and cholinergic antagonist reversal studies in normal older women, examinations of the neural representations of estrogen-cholinergic interactions using functional brain imaging, and studies of the ability of selective estrogen receptor modulators such as tamoxifen to interact with cholinergic-mediated cognitive performance. We also discuss the implications of these studies for the underlying hypotheses of cholinergic-estrogen interactions and cognitive aging, and indications for prophylactic and therapeutic potential that may exploit these effects. Published by Elsevier Inc.

  14. A new series of estrogen receptor modulators that display selectivity for estrogen receptor beta.

    Science.gov (United States)

    Henke, Brad R; Consler, Thomas G; Go, Ning; Hale, Ron L; Hohman, Dana R; Jones, Stacey A; Lu, Amy T; Moore, Linda B; Moore, John T; Orband-Miller, Lisa A; Robinett, R Graham; Shearin, Jean; Spearing, Paul K; Stewart, Eugene L; Turnbull, Philip S; Weaver, Susan L; Williams, Shawn P; Wisely, G Bruce; Lambert, Millard H

    2002-12-05

    A series of 1,3,5-triazine-based estrogen receptor (ER) modulators that are modestly selective for the ERbeta subtype are reported. Compound 1, which displayed modest potency and selectivity for ERbeta vs ERalpha, was identified via high-throughput screening utilizing an ERbeta SPA-based binding assay. Subsequent analogue preparation resulted in the identification of compounds such as 21 and 43 that display 25- to 30-fold selectivity for ERbeta with potencies in the 10-30 nM range. These compounds profile as full antagonists at ERbeta and weak partial agonists at ERalpha in a cell-based reporter gene assay. In addition, the X-ray crystal structure of compound 15 complexed with the ligand binding domain of ERbeta has been solved and was utilized in the design of more conformationally restrained analogues such as 31 in an attempt to increase selectivity for the ERbeta subtype.

  15. Detection of estrogenic activity in sediment-associated compounds using in vitro reporter gene assays

    NARCIS (Netherlands)

    Legler, J.; Dennekamp, M.; Vethaak, A.D.; Brouwer, A.; Koeman, J.H.; Burg, van der B.; Murk, A.J.

    2002-01-01

    Sediments may be the ultimate sink for persistent (xeno-) estrogenic compounds released into the aquatic environment. Sediment-associated estrogenic potency was measured with an estrogen receptor-mediated luciferase reporter gene (ER-CALUX) assay and compared with a recombinant yeast screen. The

  16. Development of a rapid yeast estrogen bioassay, based on the expression of green fluorescent protein

    NARCIS (Netherlands)

    Bovee, T.F.H.; Helsdingen, R.J.R.; Koks, P.D.; Kuiper, H.A.; Hoogenboom, L.A.P.; Keijer, J.

    2004-01-01

    The aim of this study was to develop an estrogen transcription activation assay that is sensitive, fast and easy to use in the routine screening of estrogen activity in complex matrices such as agricultural products. Recombinant yeast cells were constructed that express the human estrogen receptor ¿

  17. Melanocortin 4 receptor is not required for estrogenic regulations on energy homeostasis and reproduction

    Science.gov (United States)

    Brain estrogen receptor-a (ERa) is essential for estrogenic regulation of energy homeostasis and reproduction. We previously showed that ERa expressed by pro-opiomelanocortin (POMC) neurons mediates estrogen's effects on food intake, body weight, negative regulation of hypothalamic–pituitary–gonadal...

  18. DNA Repair, Redox Regulation and Modulation of Estrogen Receptor Alpha Mediated Transcription

    Science.gov (United States)

    Curtis-Ducey, Carol Dianne

    2009-01-01

    Interaction of estrogen receptor [alpha] (ER[alpha]) with 17[beta]-estradiol (E[subscript 2]) facilitates binding of the receptor to estrogen response elements (EREs) in target genes, which in turn leads to recruitment of coregulatory proteins. To better understand how estrogen-responsive genes are regulated, our laboratory identified a number of…

  19. Influence of Sex and Estrogen on Musculotendinous Protein Turnover at Rest and After Exercise

    DEFF Research Database (Denmark)

    Hansen, Mette; Kjær, Michael

    2014-01-01

    Women differ from men with regard to muscle and tendon, most likely because of sex differences in estrogen. The present experimental findings suggest the hypothesis that estrogen has an anabolic effect on muscle primarily by lowering the protein turnover and enhancing sensitivity to resistance...... training. Furthermore, estrogen may reduce the stiffness of tendons, an effect that may be modified by physical training....

  20. 21 CFR 862.1270 - Estrogens (total, in pregnancy) test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Estrogens (total, in pregnancy) test system. 862.1270 Section 862.1270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Test Systems § 862.1270 Estrogens (total, in pregnancy) test system. (a) Identification. As estrogens...

  1. ESTROGEN IN THE TREATMENT OF DEPRESSION: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Putu Andrika Kusuma

    2014-02-01

    Full Text Available Depression led to the decline quality of life. With more incidence in women due tohormonal cycle caused women more susceptible to depression. Hormone that fluctuatesand holds a key role in brain and nerve cells is estrogen. Estrogen in premenopausalwomen already decreases. Treatment of depression in premenopausal women who gopast the various considerations needs to consider the provision of hormonal therapy. Inthe case of patients treated with psychotherapy and pharmacotherapy in the form of 2 x20 mg Fluoxetine by mouth and hormonal therapy in the form of 1 x 2 mg Estradiol.Feasibility study to evaluate the hormonal therapy contraindications such as breastcancer also needs to be done.

  2. Postmenopausal Estrogen Therapy and Risk of Gallstone Disease

    DEFF Research Database (Denmark)

    Simonsen, Maja Hellfritzsch; Erichsen, Rune; Frøslev, Trine

    2013-01-01

    BACKGROUND: Female gender and increasing age are key risk factors for gallstone disease; therefore, postmenopausal women are at high risk. Estrogen increases cholesterol saturation of bile and may further increase gallstone risk, but population-based evidence is sparse. OBJECTIVE: Our objective......, and parity. RESULTS: We identified 16,386 cases with gallstone disease and 163,860 controls. A total of 1,425 cases (8.7 %) and 8,930 controls (5.4 %) were current estrogen users, yielding an adjusted OR for gallstone disease of 1.74 (95 % CI 1.64-1.85) compared with non-users. The corresponding adjusted...

  3. Improved profiling of estrogen metabolites by orbitrap LC/MS

    Science.gov (United States)

    Li, Xingnan; Franke, Adrian A.

    2015-01-01

    Estrogen metabolites are important biomarkers to evaluate cancer risks and metabolic diseases. Due to their low physiological levels, a sensitive and accurate method is required, especially for the quantitation of unconjugated forms of endogenous steroids and their metabolites in humans. Here, we evaluated various derivatives of estrogens for improved analysis by orbitrap LC/MS in human serum samples. A new chemical derivatization reagent was applied modifying phenolic steroids to form 1-methylimidazole-2-sulfonyl adducts. The method significantly improves the sensitivity 2–100 fold by full scan MS and targeted selected ion monitoring MS over other derivatization methods including, dansyl, picolinoyl, and pyridine-3-sulfonyl products. PMID:25543003

  4. Bazedoxifene/conjugated estrogens for managing the burden of estrogen deficiency symptoms.

    Science.gov (United States)

    Mirkin, Sebastian; Ryan, Kelly A; Chandran, Arthi B; Komm, Barry S

    2014-01-01

    The bothersome vasomotor and vaginal symptoms and bone loss that accompany the menopausal transition are associated with significant direct costs due to physician visits and medication, as well as indirect costs from reduced health-related quality of life (HRQoL) and work productivity. With life expectancies increasing, the number of postmenopausal women is also increasing, and more women are remaining in the workforce. These factors have led to an increased burden of menopausal symptoms on healthcare systems. Hormone therapy (HT) has been shown to effectively reduce menopausal symptoms and significantly increase quality-adjusted life years in postmenopausal women, particularly in women experiencing severe symptoms. However, many women discontinue use of HT before their symptoms have dissipated due to safety and tolerability concerns. The tissue selective estrogen complex (TSEC) that pairs bazedoxifene (BZA) with conjugated estrogens (CE) has been developed to provide relief of menopausal symptoms and prevent bone loss without stimulating the breast or endometrium, and to have improved tolerability compared with HT. In this context, BZA 20mg/CE 0.45 and 0.625 mg were shown to prevent bone loss and effectively treat menopausal symptoms in postmenopausal women with an intact uterus, while also demonstrating a favorable safety/tolerability profile. BZA 20mg/CE 0.45 and 0.625 mg were further associated with clinically significant improvements in HRQoL, sleep, and treatment satisfaction. Taken together, the reduction in menopausal symptoms, improvement in HRQoL, and favorable safety/tolerability profile associated with BZA/CE suggest that it is a cost-effective alternative to HT for managing the burden of menopausal symptoms. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Immune-Specific Expression and Estrogenic Regulation of the Four Estrogen Receptor Isoforms in Female Rainbow Trout (Oncorhynchus mykiss

    Directory of Open Access Journals (Sweden)

    Ayako Casanova-Nakayama

    2018-03-01

    Full Text Available Genomic actions of estrogens in vertebrates are exerted via two intracellular estrogen receptor (ER subtypes, ERα and ERβ, which show cell- and tissue-specific expression profiles. Mammalian immune cells express ERs and are responsive to estrogens. More recently, evidence became available that ERs are also present in the immune organs and cells of teleost fish, suggesting that the immunomodulatory function of estrogens has been conserved throughout vertebrate evolution. For a better understanding of the sensitivity and the responsiveness of the fish immune system to estrogens, more insight is needed on the abundance of ERs in the fish immune system, the cellular ratios of the ER subtypes, and their autoregulation by estrogens. Consequently, the aims of the present study were (i to determine the absolute mRNA copy numbers of the four ER isoforms in the immune organs and cells of rainbow trout, Oncorhynchus mykiss, and to compare them to the hepatic ER numbers; (ii to analyse the ER mRNA isoform ratios in the immune system; and, (iii finally, to examine the alterations of immune ER mRNA expression levels in sexually immature trout exposed to 17β-estradiol (E2, as well as the alterations of immune ER mRNA expression levels in sexually mature trout during the reproductive cycle. All four ER isoforms were present in immune organs—head kidney, spleen-and immune cells from head kidney and blood of rainbow trout, but their mRNA levels were substantially lower than in the liver. The ER isoform ratios were tissue- and cell-specific, both within the immune system, but also between the immune system and the liver. Short-term administration of E2 to juvenile female trout altered the ER mRNA levels in the liver, but the ERs of the immune organs and cells were not responsive. Changes of ER gene transcript numbers in immune organs and cells occurred during the reproductive cycle of mature female trout, but the changes in the immune ER profiles differed

  6. Select estrogens within the complex formulation of conjugated equine estrogens (Premarin® are protective against neurodegenerative insults: implications for a composition of estrogen therapy to promote neuronal function and prevent Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Brinton Roberta

    2006-03-01

    Full Text Available Abstract Background Results of the Women's Health Initiative Memory Study (WHIMS raised concerns regarding the timing and formulation of hormone interventions. Conjugated equine estrogens (CEE, used as the estrogen therapy in the WHIMS trial, is a complex formulation containing multiple estrogens, including several not secreted by human ovaries, as well as other biologically active steroids. Although the full spectrum of estrogenic components present in CEE has not yet been resolved, 10 estrogens have been identified. In the present study, we sought to determine which estrogenic components, at concentrations commensurate with their plasma levels achieved following a single oral dose of 0.625 mg CEE (the dose used in the WHIMS trial in women, are neuroprotective and whether combinations of those neuroprotective estrogens provide added benefit. Further, we sought, through computer-aided modeling analyses, to investigate the potential correlation of the molecular mechanisms that conferred estrogen neuroprotection with estrogen interactions with the estrogen receptor (ER. Results Cultured basal forebrain neurons were exposed to either β-amyloid25–35 or excitotoxic glutamate with or without pretreatment with estrogens followed by neuroprotection analyses. Three indicators of neuroprotection that rely on different aspects of neuronal damage and viability, LDH release, intracellular ATP level and MTT formazan formation, were used to assess neuroprotective efficacy. Results of these analyses indicate that the estrogens, 17α-estradiol, 17β-estradiol, equilin, 17α-dihydroequilin, equilinen, 17α-dihydroequilenin, 17β-dihydroequilenin, and Δ8,9-dehydroestrone were each significantly neuroprotective in reducing neuronal plasma membrane damage induced by glutamate excitotoxicity. Of these estrogens, 17β-estradiol and Δ8,9-dehydroestrone were effective in protecting neurons against β-amyloid25–35-induced intracellular ATP decline

  7. No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals

    OpenAIRE

    Beresford, N; Granger, DW; Pounds, NA; Rand-Weaver, M; White, R; Jobling, S; Routledge, EJ

    2013-01-01

    This article is made available through the Brunel Open Access Publishing Fund. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs ...

  8. Estrogenic response of bisphenol A in rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Lindholst, Christian; Pedersen, Knud Ladegaard; Pedersen, Søren Nørby

    2000-01-01

    Bisphenol A (BPA) previously shown to possess xenoestrogenic activities was administered to rainbow trout (Oncorhynchus mykiss) through a continuos flow system. The estrogenic response expressed as the induction of vitellogenin (VTG) synthesis was measured during 12 days of exposure, using a direct...

  9. Phytoestrogenic property of Labisia pumila for use as an estrogen ...

    African Journals Online (AJOL)

    Melissa

    Labisia pumila (LP), also known as Kacip Fatimah has been used by Malay women for generations for conditions related to menopausal symptoms. Though, there has been no scientific-based evidence for its efficacy as an estrogen replacement therapy (ERT), LP's use continues to be on the rise. This could be seen with ...

  10. Expression of androgen and estrogen receptors in the testicular ...

    African Journals Online (AJOL)

    enoh

    2012-04-10

    Apr 10, 2012 ... 66: 1161-1168. Oliveira CA, Mahecha GA, Carnes K, Prins GS, Saunders PT, Franca. LR, Hess RA (2004). Differential hormonal regulation of estrogen receptors ERα and ER and androgen receptor expression in rat efferent ductules. Reproduction, 128(1): 73-86. O'Shaughnessy PJ, Johnston H, Willerton L ...

  11. Comparing predicted estrogen concentrations with measurements in US waters

    International Nuclear Information System (INIS)

    Kostich, Mitch; Flick, Robert; Martinson, John

    2013-01-01

    The range of exposure rates to the steroidal estrogens estrone (E1), beta-estradiol (E2), estriol (E3), and ethinyl estradiol (EE2) in the aquatic environment was investigated by modeling estrogen introduction via municipal wastewater from sewage plants across the US. Model predictions were compared to published measured concentrations. Predictions were congruent with most of the measurements, but a few measurements of E2 and EE2 exceed those that would be expected from the model, despite very conservative model assumptions of no degradation or in-stream dilution. Although some extreme measurements for EE2 may reflect analytical artifacts, remaining data suggest concentrations of E2 and EE2 may reach twice the 99th percentile predicted from the model. The model and bulk of the measurement data both suggest that cumulative exposure rates to humans are consistently low relative to effect levels, but also suggest that fish exposures to E1, E2, and EE2 sometimes substantially exceed chronic no-effect levels. -- Highlights: •Conservatively modeled steroidal estrogen concentrations in ambient water. •Found reasonable agreement between model and published measurements. •Model and measurements agree that risks to humans are remote. •Model and measurements agree significant questions remain about risk to fish. •Need better understanding of temporal variations and their impact on fish. -- Our model and published measurements for estrogens suggest aquatic exposure rates for humans are below potential effect levels, but fish exposure sometimes exceeds published no-effect levels

  12. Prenatal Estrogens and the Development of Homosexual Orientation.

    Science.gov (United States)

    Meyer-Bahlburg, Heino F. L.; And Others

    1995-01-01

    Examines the hypothesis that prenatal estrogens contribute to the development of human sexual orientation. Several groups of women with a history of prenatal exposure to diethylstilbestrol (DES) were compared with several samples of control women. Findings showed that more DES-exposed women than controls were rated as bisexual or homosexual,…

  13. Estrogen receptor beta in prostate cancer: friend or foe?

    Science.gov (United States)

    Nelson, Adam W; Tilley, Wayne D; Neal, David E; Carroll, Jason S

    2014-08-01

    Prostate cancer is the commonest, non-cutaneous cancer in men. At present, there is no cure for the advanced, castration-resistant form of the disease. Estrogen has been shown to be important in prostate carcinogenesis, with evidence resulting from epidemiological, cancer cell line, human tissue and animal studies. The prostate expresses both estrogen receptor alpha (ERA) and estrogen receptor beta (ERB). Most evidence suggests that ERA mediates the harmful effects of estrogen in the prostate, whereas ERB is tumour suppressive, but trials of ERB-selective agents have not translated into improved clinical outcomes. The role of ERB in the prostate remains unclear and there is increasing evidence that isoforms of ERB may be oncogenic. Detailed study of ERB and ERB isoforms in the prostate is required to establish their cell-specific roles, in order to determine if therapies can be directed towards ERB-dependent pathways. In this review, we summarise evidence on the role of ERB in prostate cancer and highlight areas for future research. © 2014 Society for Endocrinology.

  14. Expression of Estrogen Alpha and Beta Receptors in Prostate ...

    African Journals Online (AJOL)

    Expression of Estrogen Alpha and Beta Receptors in Prostate Cancer and Hyperplasia: Immunohistochemical Analysis. ... Additionally, ER-α was not expressed in either luminal or basal cells in any of the 35 BPH cases. However ... Key Words: ER-α, ER-β, prostate, hyperplasia, premalignant, cancer, immunohistochemistry ...

  15. Mouse models of estrogen receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Shakur Mohibi

    2011-01-01

    Full Text Available Breast cancer is the most frequent malignancy and second leading cause of cancer-related deaths among women. Despite advances in genetic and biochemical analyses, the incidence of breast cancer and its associated mortality remain very high. About 60 - 70% of breast cancers are Estrogen Receptor alpha (ER-α positive and are dependent on estrogen for growth. Selective estrogen receptor modulators (SERMs have therefore provided an effective targeted therapy to treat ER-α positive breast cancer patients. Unfortunately, development of resistance to endocrine therapy is frequent and leads to cancer recurrence. Our understanding of molecular mechanisms involved in the development of ER-α positive tumors and their resistance to ER antagonists is currently limited due to lack of experimental models of ER-α positive breast cancer. In most mouse models of breast cancer, the tumors that form are typically ER-negative and independent of estrogen for their growth. However, in recent years more attention has been given to develop mouse models that develop different subtypes of breast cancers, including ER-positive tumors. In this review, we discuss the currently available mouse models that develop ER-α positive mammary tumors and their potential use to elucidate the molecular mechanisms of ER-α positive breast cancer development and endocrine resistance.

  16. The Determinations of Estrogen and Progesterone Receptor in Breast Cancer Cell by Radioimmunoassay Method

    International Nuclear Information System (INIS)

    Kim, Chi Yeul

    1981-01-01

    The estrogen and progesterone receptors which are bound to the cytoplasmic protein of cancer cells were measured in 20 patients with the early breast cancer by means of radioimmunoassay using charcoal. 1) The patients with estrogen receptor positive were 13 (65%) of 20 cases and with progestrone receptor positive were 7 cases (35%) in the early breast cancer. 2) Coexistence of estrogen and progesterone receptor positive was noted in 7 cases (35%). The cases of estrogen receptor positive and progesterone receptor negative were 6 cases (33.3%), while there were no cases of estrogen receptor negative with progesterone receptor positive. 3) Coincidence of estrogen and progesterone negative was noticed in 7 cases (35%). Conclusively it is considered that the measurement of estrogen and progesterone receptors has relevance as predictive value, in the response to hormonal manipulations and chemotherapy for breast cancer patients.

  17. Occurrence and removal of estrogens in Brazilian wastewater treatment plants

    International Nuclear Information System (INIS)

    Pessoa, Germana P.; Souza, Neyliane C. de; Vidal, Carla B.; Alves, Joana A.C.; Firmino, Paulo Igor M.; Nascimento, Ronaldo F.; Santos, André B. dos

    2014-01-01

    This paper evaluated the occurrence and removal efficiency of four estrogenic hormones in five biological wastewater treatment plants (WWTPs), located in the State of Ceará, Brazil. The five WWTPs comprised: two systems consisted of one facultative pond followed by two maturation ponds, one facultative pond, one activated sludge (AS) system followed by a chlorination step, and one upflow anaerobic sludge blanket (UASB) reactor followed by a chlorination step. Estrogen occurrence showed a wide variation among the analyzed influent and effluent samples. Estrone (E1) showed the highest occurrence in the influent (76%), whereas both 17β-estradiol (E2) and 17α-ethynylestradiol (EE2) presented a 52% occurrence, and the compound 17β-estradiol 17-acetate (E2-17A), a 32% one. The occurrence in the effluent samples was 48% for E1, 28% for E2, 12% for E2-17A, and 40% for EE2. The highest concentrations of E1 and EE2 hormones in the influent were 3050 and 3180 ng L −1 , respectively, whereas E2 and E2-17A had maximum concentrations of 776 and 2300 ng L −1 , respectively. The lowest efficiencies for the removal of estrogenic hormones were found in WWTP consisted of waste stabilization ponds, ranging from 54 to 79.9%. The high-rate systems (AS and UASB), which have chlorination as post-treatment, presented removal efficiencies of approximately 95%. - Highlights: • The occurrence of four endocrine disrupting chemicals was evaluated. • The removal efficiency of four hormones in low-cost plants was examined. • Estrogen occurrence showed a wide variation in influent and effluent samples. • Estrone showed the highest occurrence in the influent and the effluent samples. • WSP treatment was observed to be less effective for removing estrogens

  18. Occurrence and removal of estrogens in Brazilian wastewater treatment plants

    Energy Technology Data Exchange (ETDEWEB)

    Pessoa, Germana P. [Department of Hydraulic and Environmental Engineering, Federal University of Ceará, Rua do Contorno, S/N Campus do Pici, Bl. 713, CEP: 60455-900, Fortaleza, CE (Brazil); Souza, Neyliane C. de [Department Sanitary and Environmental Engineering, State University of Paraíba, Rua Juvêncio Arruda, S/N, Campus Universitário, Bodocongó, CEP: 58109-790, Campina Grande, PB (Brazil); Vidal, Carla B.; Alves, Joana A.C.; Firmino, Paulo Igor M. [Department of Hydraulic and Environmental Engineering, Federal University of Ceará, Rua do Contorno, S/N Campus do Pici, Bl. 713, CEP: 60455-900, Fortaleza, CE (Brazil); Nascimento, Ronaldo F. [Department of Analytical Chemistry and Physical Chemistry, Federal University of Ceará, Rua do Contorno, S/N Campus do Pici, Bl. 940, CEP: 60451-970, Fortaleza, CE (Brazil); Santos, André B. dos, E-mail: andre23@ufc.br [Department of Hydraulic and Environmental Engineering, Federal University of Ceará, Rua do Contorno, S/N Campus do Pici, Bl. 713, CEP: 60455-900, Fortaleza, CE (Brazil)

    2014-08-15

    This paper evaluated the occurrence and removal efficiency of four estrogenic hormones in five biological wastewater treatment plants (WWTPs), located in the State of Ceará, Brazil. The five WWTPs comprised: two systems consisted of one facultative pond followed by two maturation ponds, one facultative pond, one activated sludge (AS) system followed by a chlorination step, and one upflow anaerobic sludge blanket (UASB) reactor followed by a chlorination step. Estrogen occurrence showed a wide variation among the analyzed influent and effluent samples. Estrone (E1) showed the highest occurrence in the influent (76%), whereas both 17β-estradiol (E2) and 17α-ethynylestradiol (EE2) presented a 52% occurrence, and the compound 17β-estradiol 17-acetate (E2-17A), a 32% one. The occurrence in the effluent samples was 48% for E1, 28% for E2, 12% for E2-17A, and 40% for EE2. The highest concentrations of E1 and EE2 hormones in the influent were 3050 and 3180 ng L{sup −1}, respectively, whereas E2 and E2-17A had maximum concentrations of 776 and 2300 ng L{sup −1}, respectively. The lowest efficiencies for the removal of estrogenic hormones were found in WWTP consisted of waste stabilization ponds, ranging from 54 to 79.9%. The high-rate systems (AS and UASB), which have chlorination as post-treatment, presented removal efficiencies of approximately 95%. - Highlights: • The occurrence of four endocrine disrupting chemicals was evaluated. • The removal efficiency of four hormones in low-cost plants was examined. • Estrogen occurrence showed a wide variation in influent and effluent samples. • Estrone showed the highest occurrence in the influent and the effluent samples. • WSP treatment was observed to be less effective for removing estrogens.

  19. Bioassay of estrogenicity and chemical analyses of estrogens in streams across the United States associated with livestock operations

    Science.gov (United States)

    Animal manures, used as a nitrogen source for crop production, are often associated with negative impacts on nutrient levels in surface water. The concentration of estrogens in streams from these manures is of concern due to potential endocrine disruption in aquatic species. S...

  20. Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer.

    Science.gov (United States)

    Shang, Zhiqun; Li, Yanjun; Hsu, Iawen; Zhang, Minghao; Tian, Jing; Wen, Simeng; Han, Ruifa; Messing, Edward M; Chang, Chawnshang; Niu, Yuanjie; Yeh, Shuyuan

    2016-05-10

    Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette-Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence.

  1. Characterization of an estrogen-responsive element implicated in regulation of the rainbow trout estrogen receptor gene.

    Science.gov (United States)

    Le Dréan, Y; Lazennec, G; Kern, L; Saligaut, D; Pakdel, F; Valotaire, Y

    1995-08-01

    We previously reported that the expression of the rainbow trout estrogen receptor (rtER) gene is markedly increased by estradiol (E2). In this paper, we have used transient transfection assays with reporter plasmids expressing chloramphenicol acetyl transferase (CAT), linked to 5' flanking regions of the rtER gene promoter, to identify cis-elements responsible for E2 inducibility. Deletion analysis localized an estrogen-responsive element (ERE), at position +242, with one mutation on the first base compared with the consensus sequence. This element confers estrogen responsiveness to CAT reporter linked to both the herpes simplex virus thymidine kinase promoter and the homologous rtER promoter. Moreover, using a 0.2 kb fragment of the rtER promoter encompassing the ERE and the rtER DNA binding domain obtained from a bacterial expression system, DNase I footprinting experiments demonstrated a specific protection covering 20 bp (+240/+260) containing the ERE sequence. Based on these studies, we believe that this ERE sequence, identified in the rtER gene promoter, may be a major cis-acting element involved in the regulation of the gene by estrogen.

  2. Estrogenic activity and estrogen receptor β binding of the UV filter 3-benzylidene camphor Comparison with 4-methylbenzylidene camphor

    International Nuclear Information System (INIS)

    Schlumpf, Margret; Jarry, Hubert; Wuttke, Wolfgang; Ma, Risheng; Lichtensteiger, Walter

    2004-01-01

    UV filters represent new classes of estrogenic [Environ. Health Perspect. 109 (2001) 239] or antiandrogenic [Toxicol. Sci. 74 (2003) 43] chemicals. We tested 3-benzylidene camphor (3-BC), reported as estrogenic in fish [Pharmacol. Toxicol. 91 (2002) 204], and mammalian systems in comparison to 4-methylbenzylidene camphor (4-MBC), shown to be active in rats, and analyzed binding to estrogen receptor subtypes. 3-BC and 4-MBC stimulated MCF-7 cell proliferation (EC 50 : 0.68 and 3.9 μM). The uterotrophic assay of 3-BC (oral gavage) in immature rats showed unexpected potency with ED50 45.3 mg/kg per day; lowest effective dose 2 mg/kg per day, and maximum effect with 70% of ethinylestradiol. After comparing with literature data, we found that the oral 3-BC was considerably more potent than oral bisphenol A and almost as active as subcutaneous genistein. 3-BC and 4-MBC displaced 16α 125 I-estradiol from porcine uterine cytosolic receptors (IC 50 : 14.5 and 112 μM), and from recombinant human estrogen receptor β (hERβ) (IC 50 : 3-BC, 11.8 μM; 4-MBC, 35.3 μM), whereas no displacement was detected at human estrogen receptor α (hERα) up to 3 mM. This subtype selectivity makes the two camphor derivatives interesting model compounds. Their activity on immature rat uterus is not easily explained by ERβ activation. It cannot be excluded that active metabolites with possibly different receptor binding characteristics are formed in vivo

  3. Triclosan Lacks (Anti-Estrogenic Effects in Zebrafish Cells but Modulates Estrogen Response in Zebrafish Embryos

    Directory of Open Access Journals (Sweden)

    Hélène Serra

    2018-04-01

    Full Text Available Triclosan (TCS, an antimicrobial agent widely found in the aquatic environment, is suspected to act as an endocrine disrupting compound, however mechanistic information is lacking in regards to aquatic species. This study assessed the ability of TCS to interfere with estrogen receptor (ER transcriptional activity, in zebrafish-specific in vitro and in vivo reporter gene assays. We report that TCS exhibits a lack of either agonistic or antagonistic effects on a panel of ER-expressing zebrafish (ZELH-zfERα and -zfERβ and human (MELN cell lines. At the organism level, TCS at concentrations of up to 0.3 µM had no effect on ER-regulated brain aromatase gene expression in transgenic cyp19a1b-GFP zebrafish embryos. At a concentration of 1 µM, TCS interfered with the E2 response in an ambivalent manner by potentializing a low E2 response (0.625 nM, but decreasing a high E2 response (10 nM. Altogether, our study suggests that while modulation of ER-regulated genes by TCS may occur in zebrafish, it does so irrespective of a direct binding and activation of zfERs.

  4. Identification of estrogen responsive genes using esophageal squamous cell carcinoma (ESCC) as a model

    KAUST Repository

    Essack, Magbubah

    2012-10-26

    Background: Estrogen therapy has positively impact the treatment of several cancers, such as prostate, lung and breast cancers. Moreover, several groups have reported the importance of estrogen induced gene regulation in esophageal cancer (EC). This suggests that there could be a potential for estrogen therapy for EC. The efficient design of estrogen therapies requires as complete as possible list of genes responsive to estrogen. Our study develops a systems biology methodology using esophageal squamous cell carcinoma (ESCC) as a model to identify estrogen responsive genes. These genes, on the other hand, could be affected by estrogen therapy in ESCC.Results: Based on different sources of information we identified 418 genes implicated in ESCC. Putative estrogen responsive elements (EREs) mapped to the promoter region of the ESCC genes were used to initially identify candidate estrogen responsive genes. EREs mapped to the promoter sequence of 30.62% (128/418) of ESCC genes of which 43.75% (56/128) are known to be estrogen responsive, while 56.25% (72/128) are new candidate estrogen responsive genes. EREs did not map to 290 ESCC genes. Of these 290 genes, 50.34% (146/290) are known to be estrogen responsive. By analyzing transcription factor binding sites (TFBSs) in the promoters of the 202 (56+146) known estrogen responsive ESCC genes under study, we found that their regulatory potential may be characterized by 44 significantly over-represented co-localized TFBSs (cTFBSs). We were able to map these cTFBSs to promoters of 32 of the 72 new candidate estrogen responsive ESCC genes, thereby increasing confidence that these 32 ESCC genes are responsive to estrogen since their promoters contain both: a/mapped EREs, and b/at least four cTFBSs characteristic of ESCC genes that are responsive to estrogen. Recent publications confirm that 47% (15/32) of these 32 predicted genes are indeed responsive to estrogen.Conclusion: To the best of our knowledge our study is the first

  5. Identification of estrogen responsive genes using esophageal squamous cell carcinoma (ESCC) as a model

    KAUST Repository

    Essack, Magbubah; MacPherson, Cameron Ross; Schmeier, Sebastian; Bajic, Vladimir B.

    2012-01-01

    Background: Estrogen therapy has positively impact the treatment of several cancers, such as prostate, lung and breast cancers. Moreover, several groups have reported the importance of estrogen induced gene regulation in esophageal cancer (EC). This suggests that there could be a potential for estrogen therapy for EC. The efficient design of estrogen therapies requires as complete as possible list of genes responsive to estrogen. Our study develops a systems biology methodology using esophageal squamous cell carcinoma (ESCC) as a model to identify estrogen responsive genes. These genes, on the other hand, could be affected by estrogen therapy in ESCC.Results: Based on different sources of information we identified 418 genes implicated in ESCC. Putative estrogen responsive elements (EREs) mapped to the promoter region of the ESCC genes were used to initially identify candidate estrogen responsive genes. EREs mapped to the promoter sequence of 30.62% (128/418) of ESCC genes of which 43.75% (56/128) are known to be estrogen responsive, while 56.25% (72/128) are new candidate estrogen responsive genes. EREs did not map to 290 ESCC genes. Of these 290 genes, 50.34% (146/290) are known to be estrogen responsive. By analyzing transcription factor binding sites (TFBSs) in the promoters of the 202 (56+146) known estrogen responsive ESCC genes under study, we found that their regulatory potential may be characterized by 44 significantly over-represented co-localized TFBSs (cTFBSs). We were able to map these cTFBSs to promoters of 32 of the 72 new candidate estrogen responsive ESCC genes, thereby increasing confidence that these 32 ESCC genes are responsive to estrogen since their promoters contain both: a/mapped EREs, and b/at least four cTFBSs characteristic of ESCC genes that are responsive to estrogen. Recent publications confirm that 47% (15/32) of these 32 predicted genes are indeed responsive to estrogen.Conclusion: To the best of our knowledge our study is the first

  6. Estrogen signalling and the DNA damage response in hormone dependent breast cancers

    Directory of Open Access Journals (Sweden)

    C Elizabeth Caldon

    2014-05-01

    Full Text Available Estrogen is necessary for the normal growth and development of breast tissue, but high levels of estrogen are a major risk factor for breast cancer. One mechanism by which estrogen could contribute to breast cancer is via the induction of DNA damage. This perspective discusses the mechanisms by which estrogen alters the DNA damage response (DDR and DNA repair through the regulation of key effector proteins including ATM, ATR, CHK1, BRCA1 and p53 and the feedback on estrogen receptor signalling from these proteins. We put forward the hypothesis that estrogen receptor signalling converges to suppress effective DNA repair and apoptosis in favour of proliferation. This is important in hormone-dependent breast cancer as it will affect processing of estrogen-induced DNA damage, as well as other genotoxic insults. DDR and DNA repair proteins are frequently mutated or altered in estrogen responsive breast cancer which will further change the processing of DNA damage. Finally the action of estrogen signalling on DNA damage is also relevant to the therapeutic setting as the suppression of a DNA damage response by estrogen has the potential to alter the response of cancers to anti-hormone treatment or chemotherapy that induces DNA damage.

  7. Estrogens regulate the hepatic effects of Growth Hormone, a hormonal interplay with multiple fates

    Directory of Open Access Journals (Sweden)

    Leandro eFernandez-Perez

    2013-06-01

    Full Text Available The liver responds to estrogens and GH which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk with endocrine, metabolic, and sex-differentiated functions of GH. Most previous studies have been focused on the influence of estrogens on pituitary GH secretion, which has a great impact on hepatic transcriptional regulation. However, there is strong evidence that estrogens can influence the GH-regulated endocrine and metabolic functions in the human liver by acting at the level of GHR-STAT5 signaling pathway. This cross-talk is relevant because the widespread exposition of estrogen or estrogen-related compounds in human. Therefore, GH or estrogen signaling deficiency as well as the influence of estrogens on GH biology can cause a dramatic impact in liver physiology during mammalian development and in adulthood. In this review, we will summarize the current status of the influence of estrogen on GH actions in liver. A better understanding of estrogen-GH interplay in liver will lead to improved therapy of children with growth disorders and of adults with GH deficiency.

  8. The penis: a new target and source of estrogen in male reproduction.

    Science.gov (United States)

    Mowa, C N; Jesmin, S; Miyauchi, T

    2006-01-01

    In the past decade, interest and knowledge in the role of estrogen in male reproduction and fertility has gained significant momentum. More recently, the cellular distribution and activity of estrogen receptors (alpha and beta)(ER) and aromatase (estrogen synthesis) has been reported in the penis, making the penis the latest "frontier" in the study of estrogen in male reproduction. ER and aromatase are broadly and abundantly expressed in various penile compartments and cell types (erectile tissues, urethral epithelia, vascular and neuronal cells), suggesting the complexity and significance of the estrogen-ER system in penile events. Unraveling this complexity is important and will require utilization of the various resources that are now at our disposal including, animal models and human lacking or deficient in ER and aromatase and the use of advanced and sensitive techniques. Some of the obvious areas that require our attention include: 1) a comprehensive mapping of ER-alpha and -beta cellular expression in the different penile compartments and subpopulations of cells, 2) delineation of the specific roles of estrogen in the different subpopulations of cells, 3) establishing the relationship of the estrogen-ER system with the androgen-androgen receptor system, if any, and 4) characterizing the specific penile phenotypes in human and animals lacking or deficient in estrogen and ER. Some data generated thus far, although preliminary, appear to challenge the long held dogma that, overall, androgens have a regulatory monopoly of penile development and function.

  9. A RIKILT yeast estrogen bioassay (REA) for estrogen residue detection in urine of calves experimentally treated with 17ß-estradiol

    NARCIS (Netherlands)

    Divari, S.; Maria, De R.; Cannizzo, F.T.; Spada, F.; Mulasso, C.; Bovee, T.F.H.; Capra, P.; Leporati, M.; Biolatti, B.

    2010-01-01

    17ß-Estradiol is one of the most powerful sex steroids illegally used in bovine production. The objective of this study was to evaluate the application and the specificity of the RIKILT yeast estrogen bioassay (REA) for the detection of molecules with estrogenic activities in the urine of calves

  10. Biological validation of a sample preparation method for ER-CALUX bioanalysis of estrogenic activity in sediments using mixtures of xeno-estrogens

    NARCIS (Netherlands)

    Houtman, C.J.; Houten, Y.K.; Leonards, P.E.G.; Brouwer, A.; Lamoree, M.H.; Legler, J.

    2006-01-01

    The combined estrogenic effects of mixtures of environmental pollutants in the in vitro ER-CALUX (chemical activated luciferase gene expression) bioassay were examined to biologically validate a sample preparation method for the analysis of estrogenic compounds in sediment. The method used

  11. Biolonical validation of a sample preparation method for ER-CALUX bioanalysis of estrogenic activity in sediment using mixtures of xeno-estrogens

    NARCIS (Netherlands)

    Houtman, C.J.; Houten, Van Y.K.; Leonards, P.E.G.; Brouwer, A.; Lamoree, M.H.; Legler, J.

    2006-01-01

    The combined estrogenic effects of mixtures of environmental pollutants in the in vitro ER-CALUX (chemical activated luciferase gene expression) bioassay were examined to biologically validate a sample preparation method for the analysis of estrogenic compounds in sediment. The method used

  12. Comparison of in vitro estrogenic activity and estrogen concentrations in source and treated waters from 25 U.S. drinking water treatment plants

    Science.gov (United States)

    In vitro bioassays have been successfully used to screen for estrogenic activity in wastewater and surface water, however, few have been applied to treated drinking water. Here, extracts of source and treated drinking water samples were assayed for estrogenic activity using T47D...

  13. Human estrogen receptor (ESR) gene locus: PssI dimorphism

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, R T; Taylor, J E; Frossard, P M [California Biotechnology Inc., Mountain View, CA (USA); Shine, J J [Garvan Institute, Darlinghurst (Australia)

    1988-07-25

    pESR-2, a 2.1 kb partial cDNA containing the entire translated sequence of the human estrogen receptor mRNA isolated from MCF-7 human breast cancer cells, was subcloned in the Eco RI site of pBR322. PssI (PuGGNCCPy) identifies a single two-allele polymorphism with bands at either 1.7 or 1.4 kb, as well as invariant bands at 12.6, 9.3, 4.1, 3.7, 2.4, 2.2, and 1.2 kb. Its frequency was studied in 77 unrelated North American Caucasians. The human estrogen receptor gene has been localized to 6q24 -- q27 by in situ hybridization. Co-dominant segregation is demonstrated in one family (8 individuals).

  14. The estrogen hypothesis of schizophrenia implicates glucose metabolism

    DEFF Research Database (Denmark)

    Olsen, Line; Hansen, Thomas; Jakobsen, Klaus D

    2008-01-01

    expression studies have indicated an equally large set of candidate genes that only partially overlap linkage genes. A thorough assessment, beyond the resolution of current GWA studies, of the disease risk conferred by the numerous schizophrenia candidate genes is a daunting and presently not feasible task....... We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling networks...... implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated with schizophrenia...

  15. Guppy sexual behavior as an effect biomarker of estrogen mimics

    DEFF Research Database (Denmark)

    Bayley, M; Nielsen, J R; Baatrup, E

    1999-01-01

    There is widespread concern that some environmental chemicals can reduce the reproductive capability of humans and wildlife by mimicking natural estrogens and disrupting endocrine function. This potential threat to animal populations posed by xenoestrogens has, hardly surprisingly, been met...... strongly on the ability to perform the appropriate sexual behavior. The sexual display of the male guppy is strongly linked to reproductive success and is readily quantified under laboratory conditions. This preliminary study demonstrates that exposure of adult male guppies to water weakly contaminated...... with either natural estrogen (17beta-estradiol) or the xenoestrogen (4-tert-octylphenol) causes a dramatic decrease in the rate and intensity of sexual display. It is concluded that quantitative analysis of the sexual display of male guppies holds great promise as a biomarker at the organismal level...

  16. Selective estrogen receptor modulators as brain therapeutic agents

    OpenAIRE

    Arévalo, María Ángeles; Santos-Galindo, María; Lagunas, Natalia; Azcoitia, I.; García-Segura, Luis M.

    2011-01-01

    Selective estrogen receptor modulators (SERMs), used for the treatment of breast cancer, osteoporosis, and menopausal symptoms, affect the nervous system. Some SERMs trigger neuroprotective mechanisms and reduce neural damage in different experimental models of neural trauma, brain inflammation, neurodegenerative diseases, cognitive impairment, and affective disorders. New SERMs with specific actions on neurons and glial cells may represent promising therapeutic tools for the brain. © 2011 So...

  17. Effect of estrogens on boar sperm capacitation in vitro

    Czech Academy of Sciences Publication Activity Database

    Děd, Lukáš; Dostálová, Pavla; Dorosh, Andriy; Dvořáková-Hortová, K.; Pěknicová, Jana

    2010-01-01

    Roč. 8, - (2010), --- ISSN 1477-7827 R&D Projects: GA MŠk(CZ) 1M06011; GA ČR(CZ) GD523/08/H064; GA ČR(CZ) GA523/09/1793 Institutional research plan: CEZ:AV0Z50520701 Keywords : capacitation * acrosome reaction * monoclonal antibody * estrogen * flow cytometry Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.695, year: 2010

  18. Conjugated equine estrogen enhances rats' cognitive, anxiety, and social behavior

    OpenAIRE

    Walf, Alicia A.; Frye, Cheryl A.

    2008-01-01

    The ovarian hormone, 17β-estradiol (E2), has numerous targets in the body and brain, and can influence cognitive, affective, and social behavior. However, functional effects of commonly prescribed E2-based hormone therapies are less known. The effects of conjugated equine estrogen (CEE) on middle-aged female rats for cognitive (object recognition), anxiety (open field, plus maze), and social (social interaction, lordosis) behavior were compared-with vehicle. Our hypothesis that CEE would enha...

  19. The Role of Estrogen Receptor β in Prostate Cancer

    OpenAIRE

    Christoforou, Paraskevi; Christopoulos, Panagiotis F; Koutsilieris, Michael

    2014-01-01

    Although androgen receptor (AR) signaling is the main molecular tool regulating growth and function of the prostate gland, estrogen receptor β (ERβ) is involved in the differentiation of prostatic epithelial cells and numerous antiproliferative actions on prostate cancer cells. However, ERβ splice variants have been associated with prostate cancer initiation and progression mechanisms. ERβ is promising as an anticancer therapy and in the prevention of prostate cancer. Herein, we review the re...

  20. Estrogen replacement, vascular distensibility, and blood pressures in postmenopausal women.

    Science.gov (United States)

    De Meersman, R E; Zion, A S; Giardina, E G; Weir, J P; Lieberman, J S; Downey, J A

    1998-05-01

    The pathogenesis of blood pressure (BP) rise in aging women remains unexplained, and one of the many incriminating factors may include abnormalities in arteriolar resistance vessels. The aim of this study was to determine the effects of unopposed estrogen on arteriolar distensibility, baroreceptor sensitivity (BRS), BP changes, and rate-pressure product (RPP). We tested the hypotheses that estrogen replacement therapy (ERT) enhances arteriolar distensibility and ameliorates BRS, which leads to decreases in BP and RPP. Postmenopausal women participated in a single-blind crossover study; the participants of this study, after baseline measurements, were randomly assigned to receive estrogen (ERT) or a drug-free treatment with a 6-wk washout period between treatments. The single-blind design was instituted because subjects become unblinded due to physiological changes (i.e., fluid shifts, weight gain, and secretory changes) associated with estrogen intake. However, investigators and technicians involved in data collection and analyses remained blind. After each treatment, subjects performed identical autonomic tests, during which electrocardiograms, beat-by-beat BPs, and respiration were recorded. The area under the dicrotic notch of the BP wave was used as an index of arteriolar distensibility. The magnitude of the reflex bradycardia after a precipitous rise in BP was used to determine BRS. Power spectral analysis of heart rate variability was used to assess autonomic activity. BPs were recorded from resistance vessels in the finger using a beat-by-beat photoplethysmographic device. RPP, a noninvasive marker of myocardial oxygen consumption, was calculated. Repeated-measures analyses of variance revealed a significantly enhanced arteriolar distensibility and BRS after ERT (P factors in aging women.

  1. NAFLD, Estrogens, and Physical Exercise: The Animal Model

    Directory of Open Access Journals (Sweden)

    Jean-Marc Lavoie

    2012-01-01

    Full Text Available One segment of the population that is particularly inclined to liver fat accumulation is postmenopausal women. Although nonalcoholic hepatic steatosis is more common in men than in women, after menopause there is a reversal in gender distribution. At the present time, weight loss and exercise are regarded as first line treatments for NAFLD in postmenopausal women, as it is the case for the management of metabolic syndrome. In recent years, there has been substantial evidence coming mostly from the use of the animal model, that indeed estrogens withdrawal is associated with modifications of molecular markers favouring the activity of metabolic pathways ultimately leading to liver fat accumulation. In addition, the use of the animal model has provided physiological and molecular evidence that exercise training provides estrogens-like protective effects on liver fat accumulation and its consequences. The purpose of the present paper is to present information relative to the development of a state of NAFLD resulting from the absence of estrogens and the role of exercise training, emphasizing on the contribution of the animal model on these issues.

  2. [THE ROLE OF ESTROGENS IN THE CARCINOGENESIS OF LUNG CANCER].

    Science.gov (United States)

    Uchikova, E; Uchikov, A; Dimitrakova, E; Uchikov, P

    2016-01-01

    Morbidity and mortality from lung cancer has dramatically increased in women as compared to men over the past few years. Historically, smoking has been considered the major risk factor for lung cancer regardless of gender. Several recent lines of evidence implicate gender differences in the observed differences in prevalence and histologic type which cannot be explained based on the carcinogenic action of nicotine. Several recent studies underscore the importance of reproductive and hormonal factors in the carcinogenesis of lung cancer Lung cancer morbidity and mortality in Bulgaria was 16.2/100000 women and 14.6/ 100000 women, resp. Lung cancer morbidity in Europe was 39/100000 women. Lung cancer is extremely sensitive to estrogens. The latter act directly or as effect modifiers for the relationship between smoking and lung cancer. Further research examining the relationship between serum estrogen levels and the estrogen receptor expression in normal and tumor lung tissue samples can help elucidate the importance of reproductive and hormonal (exogenous and endogenous) factors in the carcinogenesis of lung cancer.

  3. Anatomical distribution of estrogen target neurons in turtle brain

    International Nuclear Information System (INIS)

    Kim, Y.S.; Stumpf, W.E.; Sar, M.

    1981-01-01

    Autoradiographic studies with [ 3 H]estradiol-17β in red-eared turtle (Pseudemys scripta elegans) show concentration and retention of radioactivity in nuclei of neurons in certain regions. Accumulations of estrogen target neurons exist in the periventricular brain with relationships to ventral extensions of the forebrain ventricles, including parolfactory, amygdaloid, septal, preoptic, hypothalamic and thalamic areas, as well as the dorsal ventricular ridge, the piriform cortex, and midbrain-pontine periaqueductal structures. The general anatomical pattern of distribution of estrogen target neurons corresponds to those observed not only in another reptile (Anolis carolinensis), but also in birds and mammals, as well as in teleosts and cyclostomes. In Pseudemys, which appears to display an intermediate degree of phylogenetic differentiation, the amygdaloid-septal-preoptic groups of estrogen target neurons constitute a continuum. In phylogenetic ascendency, e.g. in mammals, these cell populations are increasingly separated and distinct, while in phylogenetic descendency, e.g. in teleosts and cyclostomes, an amygdaloid group appears to be absent or contained within the septal-preoptic target cell population. (Auth.)

  4. Anatomical distribution of estrogen target neurons in turtle brain

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Y.S.; Stumpf, W.E.; Sar, M. (North Carolina Univ., Chapel Hill (USA))

    1981-12-28

    Autoradiographic studies with (/sup 3/H)estradiol-17..beta.. in red-eared turtle (Pseudemys scripta elegans) show concentration and retention of radioactivity in nuclei of neurons in certain regions. Accumulations of estrogen target neurons exist in the periventricular brain with relationships to ventral extensions of the forebrain ventricles, including parolfactory, amygdaloid, septal, preoptic, hypothalamic and thalamic areas, as well as the dorsal ventricular ridge, the piriform cortex, and midbrain-pontine periaqueductal structures. The general anatomical pattern of distribution of estrogen target neurons corresponds to those observed not only in another reptile (Anolis carolinensis), but also in birds and mammals, as well as in teleosts and cyclostomes. In Pseudemys, which appears to display an intermediate degree of phylogenetic differentiation, the amygdaloid-septal-preoptic groups of estrogen target neurons constitute a continuum. In phylogenetic ascendency, e.g. in mammals, these cell populations are increasingly separated and distinct, while in phylogenetic descendency, e.g. in teleosts and cyclostomes, an amygdaloid group appears to be absent or contained within the septal-preoptic target cell population.

  5. Estrogenic potential of the Venice, Italy, lagoon waters.

    Science.gov (United States)

    Pojana, Giulio; Bonfà, Angela; Busetti, Francesco; Collarin, Anna; Marcomini, Antonio

    2004-08-01

    The exposure of the Venice lagoon (Italy) to endocrine-disrupting compounds (EDCs) from different sources was investigated. Spatial and time distribution of EDC concentrations were determined in four sampling sessions (December 2001-May 2002) by solid phase extraction followed by high-performance liquid chromatography separation coupled with mass spectrometry detection via electrospray interface (SPE-HPLC-ESI-MS), which allowed identification of natural (estradiol, estrone) and synthetic estrogenic compounds, both steroidal (ethinylestradiol, mestranol) and nonsteroidal (benzophenone, bisphenol-A, nonylphenol, nonylphenol monoethoxylate carboxylate). No significant differences in the EDC distribution were observed between stations located near selected sources (raw sewage from the historical center of Venice, treated municipal and industrial effluents from sewage treatment plants, and areas undergoing the inflow of rivers). While synthetic nonsteroidal analytes were recorded in the 1 to 1040 ng/L range (average concentration: 34 ng/L), steroidal EDC (estradiol, ethinylestradiol) concentrations were lower (1-125 ng/L; average concentration: 8 ng/L). The estrogenic activity of lagoon waters was estimated in terms of estradiol equivalent concentration (EEQ) by applying the estradiol equivalency factors (EEFs). Steroidal EDCs (estradiol, ethinylestradiol) contributed >97% to the total potential estrogenicity of the waters, which accounted for 4 to 172 ng/L (average: 25 ng/L), as total EEQs. These levels are likely to pose adverse effects on the Venice lagoon aquatic organisms.

  6. Estrogenic activity of zinc pyrithione: an and study

    Directory of Open Access Journals (Sweden)

    Kyung Sik Yoon

    2017-02-01

    Full Text Available Zinc pyrithione (ZP is commonly used to prevent dandruff and seborrheic dermatitis. Many consumers are exposed daily to high doses of ZP, causing serious concerns about its toxicity. The reproductive and developmental toxicities were previously reported in pregnant rats. However, the estrogenic activity of ZP at varying degrees of exposure has been rarely studied. Thus, we performed an uterotrophic assay, E-screen assay, and gene expression profiling to assess the estrogenic activity of ZP. For the uterotrophic assay, ZP (2, 10, or 50 mg/kg/d was subcutaneously administered to ovariectomized rats every day for three days. Uteri were extracted 24 hours after the last dose. Then, wet and blotted uterine weights were measured. For the E-screen essay, MCF-7 cells (a breast cancer cell line were exposed to 10-9 to 10-6 M of ZP, and cell proliferation was then measured. For the gene expression analysis, changes of gene expression levels in uterine samples taken for the uterotrophic assay were analyzed. In the uterotrophic assay, the concentration of ZP had no significant effect on uterine weight. In the E-screen assay, ZP at any concentration showed no significant increase in MCF-7 cell proliferation, compared to the control group. However, 10-6 M of ZP significantly reduced cell viability. The changes in gene expression slightly differed between the ZP and control groups. The in vivo and in vitro assays, together with gene expression analysis, demonstrated that ZP showed no significant estrogenic activity.

  7. Why estrogens matter for behavior and brain health.

    Science.gov (United States)

    Galea, Liisa A M; Frick, Karyn M; Hampson, Elizabeth; Sohrabji, Farida; Choleris, Elena

    2017-05-01

    The National Institutes of Health (NIH) has required the inclusion of women in clinical studies since 1993, which has enhanced our understanding of how biological sex affects certain medical conditions and allowed the development of sex-specific treatment protocols. However, NIH's policy did not previously apply to basic research, and the NIH recently introduced a new policy requiring all new grant applications to explicitly address sex as a biological variable. The policy itself is grounded in the results of numerous investigations in animals and humans illustrating the existence of sex differences in the brain and behavior, and the importance of sex hormones, particularly estrogens, in regulating physiology and behavior. Here, we review findings from our laboratories, and others, demonstrating how estrogens influence brain and behavior in adult females. Research from subjects throughout the adult lifespan on topics ranging from social behavior, learning and memory, to disease risk will be discussed to frame an understanding of why estrogens matter to behavioral neuroscience. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Prenatal lignan exposures, pregnancy urine estrogen profiles and birth outcomes

    International Nuclear Information System (INIS)

    Tang, Rong; Chen, Minjian; Zhou, Kun; Chen, Daozhen; Yu, Jing; Hu, Weiyue; Song, Ling; Hang, Bo; Wang, Xinru; Xia, Yankai

    2015-01-01

    During pregnancy, human exposure to endogenous estrogens and xenoestrogens (such as lignans) may comprehensively impact the gestational maintenance and fetal growth. We measured the concentrations of 5 lignans and the profile of 13 estrogen metabolites (EMs) in the urine samples of 328 pregnant women and examined their associations with birth outcomes. We found significantly positive associations between gestational age and urinary matairesinol (MAT), enterodiol (END) and enterolactone (ENL), as well as 16-hydroxylation pathway EMs. There were consistently positive relationships between END and the 16-hydroxylation pathway EMs. The positive relationships of MAT, END and ENL exposures with the length of gestation were mainly in the low exposure strata of the levels of these EMs. This study reveals that MAT, END and ENL as well as 16-hydroxylation pathway EMs are associated with birth outcomes, and that there are interactive relationships between lignans and 16-hydroxylation pathway EMs with birth outcomes. - Highlights: • We examined relations between prenatal lignan exposures and birth outcomes. • We examined relations between pregnancy urine estrogen profiles and birth outcomes. • MAT, END and ENL are associated with birth outcomes. • 16-hydroxylation pathway EMs are associated with birth outcomes. • There are interactive relationships between ligans and EMs with birth outcomes. - Prenatal lignan exposures and EM levels were interactively related to birth outcomes

  9. Social memory associated with estrogen receptor polymorphisms in women

    Science.gov (United States)

    Karlsson, Sara; Henningsson, Susanne; Hovey, Daniel; Zettergren, Anna; Jonsson, Lina; Cortes, Diana S.; Melke, Jonas; Laukka, Petri; Fischer, Håkan

    2016-01-01

    The ability to recognize the identity of faces and voices is essential for social relationships. Although the heritability of social memory is high, knowledge about the contributing genes is sparse. Since sex differences and rodent studies support an influence of estrogens and androgens on social memory, polymorphisms in the estrogen and androgen receptor genes (ESR1, ESR2, AR) are candidates for this trait. Recognition of faces and vocal sounds, separately and combined, was investigated in 490 subjects, genotyped for 10 single nucleotide polymorphisms (SNPs) in ESR1, four in ESR2 and one in the AR. Four of the associations survived correction for multiple testing: women carrying rare alleles of the three ESR2 SNPs, rs928554, rs1271572 and rs1256030, in linkage disequilibrium with each other, displayed superior face recognition compared with non-carriers. Furthermore, the uncommon genotype of the ESR1 SNP rs2504063 was associated with better recognition of identity through vocal sounds, also specifically in women. This study demonstrates evidence for associations in women between face recognition and variation in ESR2, and recognition of identity through vocal sounds and variation in ESR1. These results suggest that estrogen receptors may regulate social memory function in humans, in line with what has previously been established in mice. PMID:26955855

  10. Multiple estrogen receptor subtypes influence ingestive behavior in female rodents.

    Science.gov (United States)

    Santollo, Jessica; Daniels, Derek

    2015-12-01

    Postmenopausal women are at an increased risk of obesity and cardiovascular-related diseases. This is attributable, at least in part, to loss of the ovarian hormone estradiol, which inhibits food and fluid intake in humans and laboratory animal models. Although the hypophagic and anti-dipsogenic effects of estradiol have been well documented for decades, the precise mechanisms underlying these effects are not fully understood. An obvious step toward addressing this open question is identifying which estrogen receptor subtypes are involved and what intracellular processes are involved. This question, however, is complicated not only by the variety of estrogen receptor subtypes that exist, but also because many subtypes have multiple locations of action (i.e. in the nucleus or in the plasma membrane). This review will highlight our current understanding of the roles that specific estrogen receptor subtypes play in mediating estradiol's anorexigenic and anti-dipsogenic effects along with highlighting the many open questions that remain. This review will also describe recent work being performed by our laboratory aimed at answering these open questions. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Modulation of Estrogen Chemical Carcinogenesis by Botanical Supplements used for Postmenopausal Women’s Health

    Science.gov (United States)

    Snelten, Courtney S.; Dietz, Birgit; Bolton, Judy L.

    2012-01-01

    Breast cancer risk has been associated with long-term estrogen exposure including traditional hormone therapy (HT, formally hormone replacement therapy). To avoid traditional HT and associated risks, women have been turning to botanical supplements such as black cohosh, red clover, licorice, hops, dong gui, and ginger to relieve menopausal symptoms despite a lack of efficacy evidence. The mechanisms of estrogen carcinogenesis involve both hormonal and chemical pathways. Botanical supplements could protect women from estrogen carcinogenesis by modulating key enzymatic steps [aromatase, P4501B1, P4501A1, catechol-O-methyltransferase (COMT), NAD(P)H quinone oxidoreductase 1 (NQO1), and reactive oxygen species (ROS) scavenging] in estradiol metabolism leading to estrogen carcinogenesis as outlined in Figure 1. This review summarizes the influence of popular botanical supplements used for women’s health on these key steps in the estrogen chemical carcinogenesis pathway, and suggests that botanical supplements may have added chemopreventive benefits by modulating estrogen metabolism. PMID:24223609

  12. Estrogen and the aging brain: an elixir for the weary cortical network.

    Science.gov (United States)

    Dumitriu, Dani; Rapp, Peter R; McEwen, Bruce S; Morrison, John H

    2010-08-01

    The surprising discovery in 1990 that estrogen modulates hippocampal structural plasticity launched a whole new field of scientific inquiry. Over the past two decades, estrogen-induced spinogenesis has been described in several brain areas involved in cognition in a number of species, in both sexes and on multiple time scales. Exploration into the interaction between estrogen and aging has illuminated some of the hormone's neuroprotective effects, most notably on age-related cognitive decline in nonhuman primates. Although there is still much to be learned about the mechanisms by which estrogen exerts its actions, key components of the signal transduction pathways are beginning to be elucidated and nongenomic actions via membrane bound estrogen receptors are of particular interest. Future studies are focused on identifying the most clinically relevant hormone treatment, as well as the potential identification of new therapeutics that can prevent or reverse age-related cognitive impairment by intercepting specific signal transduction pathways initiated by estrogen.

  13. Expression of estrogen and progesterone receptors in astrocytomas: a literature review

    Directory of Open Access Journals (Sweden)

    Cléciton Braga Tavares

    Full Text Available Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression.

  14. Expression of estrogen and progesterone receptors in astrocytomas: a literature review

    Science.gov (United States)

    Tavares, Cléciton Braga; Gomes-Braga, Francisca das Chagas Sheyla Almeida; Costa-Silva, Danylo Rafhael; Escórcio-Dourado, Carla Solange; Borges, Umbelina Soares; Conde, Airton Mendes; da Conceição Barros-Oliveira, Maria; Sousa, Emerson Brandão; da Rocha Barros, Lorena; Martins, Luana Mota; Facina, Gil; da-Silva, Benedito Borges

    2016-01-01

    Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression. PMID:27626480

  15. Effect of estrogen withdrawal on energy-rich phosphates and prediction of estrogen dependence monitored by in vivo 31P magnetic resonance spectroscopy of four human breast cancer xenografts

    DEFF Research Database (Denmark)

    Kristensen, C A; Kristjansen, P E; Brünner, N

    1995-01-01

    The effect of estrogen withdrawal on energy metabolism was studied in four human breast cancer xenografts: the estrogen-dependent MCF-7 and ZR75-1 and the estrogen-independent ZR75/LCC-3 and MDA-MB-231. The tumors were grown in ovariectomized nude mice with a s.c. implanted estrogen pellet. After......-clamped tumors prepared 14 days after estrogen removal were analyzed for ATP and phosphocreatine content. Our findings suggest a correlation between estrogen withdrawal and the steady-state concentrations of ATP, phosphocreatine, and Pi in human breast cancer xenografts. Discrimination analysis...

  16. Novel estrogen receptor-related Transcripts in Marisa cornuarietis; a freshwater snail with reported sensitivity to estrogenic chemicals.

    Science.gov (United States)

    Bannister, Richard; Beresford, Nicola; May, Denise; Routledge, Edwin J; Jobling, Susan; Rand-Weaver, Mariann

    2007-04-01

    We have isolated novel molluskan steroid receptor transcripts orthologous to vertebrate estrogen receptors (ERs) and estrogen receptor-related receptors (ERRs) from the freshwater snail Marisa cornuarietis. Radiolabeled ligand binding analyses showed that neither recombinant receptor protein specifically bound 17beta-estradiol over the range applied (0.3-9.6 nM). These novel receptor transcripts have thus been designated mcER-like and mcERR respectively. Quantitative PCR revealed mcER-like to be expressed ubiquitously throughout a range of male and female structures studied, including neural and reproductive tissues. Highest absolute levels were seen in the male penis-sheath complex. The mcERR mRNA was also expressed ubiquitously throughout all male and female tissues analyzed here, with very low absolute transcript numbers in female accessory sex structures compared to other tissues.

  17. Oleocanthal Modulates Estradiol-Induced Gene Expression Involving Estrogen Receptor α.

    Science.gov (United States)

    Keiler, Annekathrin Martina; Djiogue, Sefirin; Ehrhardt, Tino; Zierau, Oliver; Skaltsounis, Leandros; Halabalaki, Maria; Vollmer, Günter

    2015-09-01

    Oleocanthal is a bioactive compound from olive oil. It has attracted considerable attention as it is anti-inflammatory, antiproliferative, and has been shown to possess neuroprotective properties in vitro and in vivo. Delineated from its polyphenolic structure, the aim of this study was to characterize oleocanthal towards estrogenic properties. This might contribute to partly explain the beneficial effects described for the Mediterranean diet. Estrogenic properties of oleocanthal were assessed by different methods: a) stimulation of reporter gene activity in MVLN or RNDA cells either expressing estrogen receptor α or β, b) stimulation of luciferase reporter gene activity in U2OS osteosarcoma cells expressing estrogen receptor α or β, and c) elucidation of the impact on estradiol-induced gene expression in U2OS cells transduced with both estrogen receptors. Depending on the cell line origin, oleocanthal inhibited luciferase activity (MVLN, U2OS-estrogen receptor β) or weakly induced reporter gene activity at 10 µM in U2OS-estrogen receptor α cells. However, oleocanthal inhibited stimulation of luciferase activity by estradiol from both estrogen receptors. Oleocanthal, if given alone, did not stimulate gene expression in U2OS cells, but it significantly modulated the response of estradiol. Oleocanthal enhanced the effect of estradiol on the regulation of those genes, which are believed to be regulated through heterodimeric estrogen receptors. As the estrogenic response pattern of oleocanthal is rather unique, we compared the results obtained with oleacein. Oleocanthal binds to both estrogen receptors inducing estradiol-agonistic or antiagonistic effects depending on the cell line. Regarding regulation of gene expression in U2OS-estrogen receptor α/β cells, oleocanthal and oleacein enhanced estradiol-mediated regulation of heterodimer-regulated genes. Georg Thieme Verlag KG Stuttgart · New York.

  18. Identification of estrogen target genes during zebrafish embryonic development through transcriptomic analysis.

    Directory of Open Access Journals (Sweden)

    Ruixin Hao

    Full Text Available Estrogen signaling is important for vertebrate embryonic development. Here we have used zebrafish (Danio rerio as a vertebrate model to analyze estrogen signaling during development. Zebrafish embryos were exposed to 1 µM 17β-estradiol (E2 or vehicle from 3 hours to 4 days post fertilization (dpf, harvested at 1, 2, 3 and 4 dpf, and subjected to RNA extraction for transcriptome analysis using microarrays. Differentially expressed genes by E2-treatment were analyzed with hierarchical clustering followed by biological process and tissue enrichment analysis. Markedly distinct sets of genes were up and down-regulated by E2 at the four different time points. Among these genes, only the well-known estrogenic marker vtg1 was co-regulated at all time points. Despite this, the biological functional categories targeted by E2 were relatively similar throughout zebrafish development. According to knowledge-based tissue enrichment, estrogen responsive genes were clustered mainly in the liver, pancreas and brain. This was in line with the developmental dynamics of estrogen-target tissues that were visualized using transgenic zebrafish containing estrogen responsive elements driving the expression of GFP (Tg(5xERE:GFP. Finally, the identified embryonic estrogen-responsive genes were compared to already published estrogen-responsive genes identified in male adult zebrafish (Gene Expression Omnibus database. The expressions of a few genes were co-regulated by E2 in both embryonic and adult zebrafish. These could potentially be used as estrogenic biomarkers for exposure to estrogens or estrogenic endocrine disruptors in zebrafish. In conclusion, our data suggests that estrogen effects on early embryonic zebrafish development are stage- and tissue- specific.

  19. Profile of bazedoxifene/conjugated estrogens for the treatment of estrogen deficiency symptoms and osteoporosis in women at risk of fracture

    Directory of Open Access Journals (Sweden)

    Rossini M

    2013-07-01

    Full Text Available Maurizio Rossini,1 Stefano Lello,2 Ignazio Sblendorio,3 Ombretta Viapiana,1 Elena Fracassi,1 Silvano Adami,1 Davide Gatti11Department of Medicine, Rheumatology Unit, University of Verona, Italy; 2Endocrinological Gynecology, Pathophysiology of Menopause and Osteoporosis, Dermopathic Institute of Immacolata, Roma, Italy; 3Medical Coach Italia Center, Bari, ItalyAbstract: Decreasing levels of estrogens during menopause are associated with reduced bone density and an increased risk of osteoporosis. Many women also experience bothersome vasomotor and vaginal symptoms during the menopausal transition. Results of systematic reviews and meta-analyses of randomized controlled trials have shown that both systemic estrogen therapy or hormone therapy (estrogen combined with a progestin are useful to prevent bone loss, and they are the most effective treatment for such climacteric symptoms as hot flushes, sweating, vaginal dryness, and dyspareunia. Unfortunately, estrogen therapy and hormone therapy increase the risk of endometrial and breast cancer, respectively. The selective estrogen receptor modulators (SERMs result in positive estrogenic effects on bone, with no negative effects on the endometrium and breast but do not provide relief from postmenopausal symptoms. The combination of a SERM with estrogen as a tissue selective estrogen complex (TSEC is a new strategy for the prevention of bone loss and the treatment of climacteric symptoms. This combination is particularly interesting from a clinical point of view, taking into account that estrogen alone did not increase breast cancer risk by the Women's Health Initiative. TSEC is hypothesized to provide the benefits of estrogen-alone therapy, with an improved tolerability profile because the SERM component can make possible the elimination of progestin. The objective of this review was to critically evaluate the evidence from the reports published to date on the use of bazedoxifene (a third

  20. Regulation of the intronic promoter of rat estrogen receptor alpha gene, responsible for truncated estrogen receptor product-1 expression.

    Science.gov (United States)

    Schausi, Diane; Tiffoche, Christophe; Thieulant, Marie-Lise

    2003-07-01

    We have characterized the intronic promoter of the rat estrogen receptor (ER) alpha gene, responsible for the lactotrope-specific truncated ER product (TERP)-1 isoform expression. Transcriptional regulation was investigated by transient transfections using 5'-deletion constructs. TERP promoter constructs were highly active in MMQ cells, a pure lactotrope cell line, whereas a low basal activity was detected in alphaT3-1 gonadotrope cells or in COS-7 monkey kidney cells. Serial deletion analysis revealed that 1) a minimal -693-bp region encompassing the TATA box is sufficient to allow lactotrope-specific expression; 2) the promoter contains strong positive cis-acting elements both in the distal and proximal regions, and 3) the region spanning the -1698/-1194 region includes repressor elements. Transient transfection studies, EMSAs, and gel shifts demonstrated that estrogen activates the TERP promoter via an estrogen-responsive element (ERE1) located within the proximal region. Mutation of ERE1 site completely abolishes the estradiol-dependent transcription, indicating that ERE1 site is sufficient to confer estrogen responsiveness to TERP promoter. In addition, ERalpha action was synergized by transfection of the pituitary-specific factor Pit-1. EMSAs showed that a single Pit-1 DNA binding element in the vicinity of the TATA box is sufficient to confer response by the TERP promoter. In conclusion, we demonstrated, for the first time, that TERP promoter regulation involves ERE and Pit-1 cis-elements and corresponding trans-acting factors, which could play a role in the physiological changes that occur in TERP-1 transcription in lactotrope cells.

  1. Hispolon inhibits the growth of estrogen receptor positive human breast cancer cells through modulation of estrogen receptor alpha

    International Nuclear Information System (INIS)

    Jang, Eun Hyang; Jang, Soon Young; Cho, In-Hye; Hong, Darong; Jung, Bom; Park, Min-Ju; Kim, Jong-Ho

    2015-01-01

    Human estrogen receptor α (ERα) is a nuclear transcription factor that is a major therapeutic target in breast cancer. The transcriptional activity of ERα is regulated by certain estrogen-receptor modulators. Hispolon, isolated from Phellinus linteus, a traditional medicinal mushroom called Sanghwang in Korea, has been used to treat various pathologies, such as inflammation, gastroenteric disorders, lymphatic diseases, and cancers. In this latter context, Hispolon has been reported to exhibit therapeutic efficacy against various cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer, and gastric cancer cells. However, ERα regulation by Hispolon has not been reported. In this study, we investigated the effects of Hispolon on the growth of breast cancer cells. We found that Hispolon decreased expression of ERα at both mRNA and the protein levels in MCF7 and T47D human breast cancer cells. Luciferase reporter assays showed that Hispolon decreased the transcriptional activity of ERα. Hispolon treatment also inhibited expression of the ERα target gene pS2. We propose that Hispolon, an anticancer drug extracted from natural sources, inhibits cell growth through modulation of ERα in estrogen-positive breast cancer cells and is a candidate for use in human breast cancer chemotherapy. - Highlights: • Hispolon decreased ERα expression at both mRNA and protein levels. • Hispolon decreased ERα transcriptional activity. • Hispolon treatment inhibited expression of ERα target gene pS2. • Shikonin is a candidate chemotherapeutic target in the treatment of human breast cancer

  2. Hispolon inhibits the growth of estrogen receptor positive human breast cancer cells through modulation of estrogen receptor alpha

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Eun Hyang; Jang, Soon Young; Cho, In-Hye [Department of Pharmacy, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of); Hong, Darong [Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of); Jung, Bom; Park, Min-Ju [Department of Pharmacy, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of); Kim, Jong-Ho, E-mail: jonghokim@khu.ac.kr [Department of Pharmacy, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of)

    2015-08-07

    Human estrogen receptor α (ERα) is a nuclear transcription factor that is a major therapeutic target in breast cancer. The transcriptional activity of ERα is regulated by certain estrogen-receptor modulators. Hispolon, isolated from Phellinus linteus, a traditional medicinal mushroom called Sanghwang in Korea, has been used to treat various pathologies, such as inflammation, gastroenteric disorders, lymphatic diseases, and cancers. In this latter context, Hispolon has been reported to exhibit therapeutic efficacy against various cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer, and gastric cancer cells. However, ERα regulation by Hispolon has not been reported. In this study, we investigated the effects of Hispolon on the growth of breast cancer cells. We found that Hispolon decreased expression of ERα at both mRNA and the protein levels in MCF7 and T47D human breast cancer cells. Luciferase reporter assays showed that Hispolon decreased the transcriptional activity of ERα. Hispolon treatment also inhibited expression of the ERα target gene pS2. We propose that Hispolon, an anticancer drug extracted from natural sources, inhibits cell growth through modulation of ERα in estrogen-positive breast cancer cells and is a candidate for use in human breast cancer chemotherapy. - Highlights: • Hispolon decreased ERα expression at both mRNA and protein levels. • Hispolon decreased ERα transcriptional activity. • Hispolon treatment inhibited expression of ERα target gene pS2. • Shikonin is a candidate chemotherapeutic target in the treatment of human breast cancer.

  3. Endometrial cancer in postmenopausal women with and without previous estrogen replacement treatment: comparison of clinical and histopathological characteristics

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Norup, P

    1993-01-01

    Clinical and histopathological features of postmenopausal endometrial cancer were studied in 63 patients who had received exogenous estrogens previously and in 76 patients who had never been exposed to estrogens. All treatments were primarily surgical. Estrogen users were younger than nonusers (P...... metaplasia and "foam" cells were not related to tumor grade or use of estrogens. The receptor content correlated inversely with grade but was not related to estrogen use. Duration of estrogen treatment was not associated with tumor stage and grade. Our findings support the theory that endometrial cancer...

  4. Effects of estrogen antagonists on estradiol-enhanced radiation transformation in vitro

    International Nuclear Information System (INIS)

    Umans, R.S.; Kenneddy, A.R.

    1988-01-01

    We have previously reported that radiation and 17β-estrediol can induce transformation in vitro in C3H 10T1/2 cells. In the present series of experiments, we have observed that antagonists of estrogen action, such as c-AMP activating agents(Theophylinne and dibutylc-AMP) and the antiestrogens tamoxifen, suppress radiation/17β-estradiol enhanced transformation in vitro. None of these known estrogen antagonists had a significant effect on transformation induced by radiation alone. Our results with added dibutyl c-AMP, theophylline and tamoxifen suggest that estrogen receptor complex formation may play a role in estrogen-enhanced radiation transformation in vitro (author)

  5. Urinary estrogen metabolites and self-reported infertility in women infected with Schistosoma haematobium.

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    Júlio Santos

    Full Text Available BACKGROUND: Schistosomiasis is a neglected tropical disease, endemic in 76 countries, that afflicts more than 240 million people. The impact of schistosomiasis on infertility may be underestimated according to recent literature. Extracts of Schistosoma haematobium include estrogen-like metabolites termed catechol-estrogens that down regulate estrogen receptors alpha and beta in estrogen responsive cells. In addition, schistosome derived catechol-estrogens induce genotoxicity that result in estrogen-DNA adducts. These catechol estrogens and the catechol-estrogen-DNA adducts can be isolated from sera of people infected with S. haematobium. The aim of this study was to study infertility in females infected with S. haematobium and its association with the presence of schistosome-derived catechol-estrogens. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was undertaken of female residents of a region in Bengo province, Angola, endemic for schistosomiasis haematobia. Ninety-three women and girls, aged from two (parents interviewed to 94 years were interviewed on present and previous urinary, urogenital and gynecological symptoms and complaints. Urine was collected from the participants for egg-based parasitological assessment of schistosome infection, and for liquid chromatography diode array detection electron spray ionization mass spectrometry (LC/UV-DAD/ESI-MSn to investigate estrogen metabolites in the urine. Novel estrogen-like metabolites, potentially of schistosome origin, were detected in the urine of participants who were positive for eggs of S. haematobium, but not detected in urines negative for S. haematobium eggs. The catechol-estrogens/ DNA adducts were significantly associated with schistosomiasis (OR 3.35; 95% CI 2.32-4.84; P≤0.001. In addition, presence of these metabolites was positively associated with infertility (OR 4.33; 95% CI 1.13-16.70; P≤0.05. CONCLUSIONS/SIGNIFICANCE: Estrogen metabolites occur widely in diverse

  6. Organization of Estrogen-Associated Circuits in the Mouse Primary Auditory Cortex

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    Liisa A. Tremere

    2011-01-01

    Full Text Available Sex steroid hormones influence the perceptual processing of sensory signals in vertebrates. In particular, decades of research have shown that circulating levels of estrogen correlate with hearing function. The mechanisms and sites of action supporting this sensory-neuroendocrine modulation, however, remain unknown. Here we combined a molecular cloning strategy, fluorescence in-situ hybridization and unbiased quantification methods to show that estrogen-producing and -sensitive neurons heavily populate the adult mouse primary auditory cortex (AI. We also show that auditory experience in freely-behaving animals engages estrogen-producing and -sensitive neurons in AI. These estrogen-associated networks are greatly stable, and do not quantitatively change as a result of acute episodes of sensory experience. We further demonstrate the neurochemical identity of estrogen-producing and estrogen-sensitive neurons in AI and show that these cell populations are phenotypically distinct. Our findings provide the first direct demonstration that estrogen-associated circuits are highly prevalent and engaged by sensory experience in the mouse auditory cortex, and suggest that previous correlations between estrogen levels and hearing function may be related to brain-generated hormone production. Finally, our findings suggest that estrogenic modulation may be a central component of the operational framework of central auditory networks.

  7. Estrogen-dependent changes in serum iron levels as a translator of the adverse effects of estrogen during infection: a conceptual framework.

    Science.gov (United States)

    Hamad, Mawieh; Awadallah, Samir

    2013-12-01

    Elevated levels of estrogen often associate with increased susceptibility to infection. This has been attributed to the ability of estrogen to concomitantly enhance the growth and virulence of pathogens and suppress host immunity. But the exact mechanism of how estrogen mediates such effects, especially in cases where the pathogen and/or the immune components in question do not express estrogen receptors, has yet to be elucidated. Here we propose that translating the adverse effects of estrogen during infection is dependent to a significant degree upon its ability to manipulate iron homeostasis. For elevated levels of estrogen alter the synthesis and/or activity of several factors involved in iron metabolism including hypoxia inducible factor 1α (HIF-1α) and hepcidin among others. This leads to the inhibition of hepcidin synthesis in hepatocytes and the maintenance of ferroportin (FPN) integrity on the surface of iron-releasing duodenal enterocytes, hepatocytes, and macrophages. Intact FPN permits the continuous efflux of dietary and stored iron into the circulation, which further enhances pathogen growth and virulence on the one hand and suppresses host immunity on the other. This new conceptual framework may help explain a multitude of disparate clinical and experimental observations pertinent to the relationship between estrogen and infection. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Evaluation of estrogen and G protein-coupled estrogen receptor 1 (GPER levels in drug-naïve patients with attention deficit hyperactivity disorder (ADHD

    Directory of Open Access Journals (Sweden)

    Nilfer Sahin

    2018-05-01

    Full Text Available Estrogen has a crucial role in the regulation of reproductive and neuroendocrine function and exerts its effects through two classes of receptors, nuclear and membrane estrogen receptors (mERs. G protein-coupled estrogen receptor 1 (GPER is a member of mERs, and despite limited research on the levels of GPER in patients with psychiatric diseases, a role of GPER in such conditions has been suggested. Here we evaluated serum estrogen and GPER levels in children with attention deficit hyperactivity disorder (ADHD in relation to their age- and gender-matched healthy controls. A total of 82 children were included in the study, 47 drug- naïve patients with ADHD (age: 6–12 years; male/female: 34/13 and 35 healthy controls (age: 6–12 years; male/female: 19/16. The subgroups according to ADHD types were inattentive, hyperactive/impulsive, and combined. Serum estrogen was measured using an immunoassay system, while serum GPER was determined using a commercial sandwich enzyme-linked immunosorbent assay kit. Estrogen levels in children with ADHD were similar as in control group, while GPER levels were significantly lower in ADHD group compared to controls (p < 0.05. Logistic regression analysis showed a significant association between GPER levels and ADHD (p < 0.05, and no association between estrogen levels and ADHD (p > 0.05. No significant differences were found in GPER and estrogen levels between ADHD subgroups (p > 0.05. To the best of our knowledge, this study is the first to investigate estrogen and GPER levels in ADHD. Our preliminary findings suggest a relationship between serum GPER levels and ADHD, and this should be further investigated.

  9. Estrogen-induced DNA synthesis in vascular endothelial cells is mediated by ROS signaling

    Directory of Open Access Journals (Sweden)

    Felty Quentin

    2006-04-01

    Full Text Available Abstract Background Since estrogen is known to increase vascular endothelial cell growth, elevated estrogen exposure from hormone replacement therapy or oral contraceptives has the potential to contribute in the development of abnormal proliferative vascular lesions and subsequent thickening of the vasculature. How estrogen may support or promote vascular lesions is not clear. We have examined in this study whether estrogen exposure to vascular endothelial cells increase the formation of reactive oxygen species (ROS, and estrogen-induced ROS is involved in the growth of endothelial cells. Methods The effect of estrogen on the production of intracellular oxidants and the role of estrogen-induced ROS on cell growth was studied in human umbilical vein endothelial cells. ROS were measured by monitoring the oxidation of 2'7'-dichlorofluorescin by spectrofluorometry. Endothelial cell growth was measured by a colorimetric immunoassay based on BrdU incorporation into DNA. Results Physiological concentrations of estrogen (367 fmol and 3.67 pmol triggered a rapid 2-fold increase in intracellular oxidants in endothelial cells. E2-induced ROS formation was inhibited to basal levels by cotreatment with the mitochondrial inhibitor rotenone (2 μM and xanthine oxidase inhibitor allopurinol (50 μM. Inhibitors of NAD(PH oxidase, apocynin and DPI, did not block E2-induced ROS formation. Furthermore, the NOS inhibitor, L-NAME, did not prevent the increase in E2-induced ROS. These findings indicate both mitochondria and xanthine oxidase are the source of ROS in estrogen treated vascular endothelial cells. E2 treated cells showed a 2-fold induction of BrdU incorporation at 18 h which was not observed in cells exposed to vehicle alone. Cotreatment with ebselen (20 μM and NAC (1 mM inhibited E2-induced BrdU incorporation without affecting the basal levels of DNA synthesis. The observed inhibitory effect of NAC and ebselen on E2-induced DNA synthesis was also shown

  10. Estrogen: The necessary evil for human health, and ways to tame it.

    Science.gov (United States)

    Patel, Seema; Homaei, Ahmad; Raju, Akondi Butchi; Meher, Biswa Ranjan

    2018-06-01

    Estrogen is a pivotal enzyme for survival and health in both genders, though their quantum, tropism, tissue-specific distribution, and receptor affinity varies with different phases of life. Converted from androgen via aromatase enzyme, this hormone is indispensable to glucose homeostasis, immune robustness, bone health, cardiovascular health, fertility, and neural functions. However, estrogen is at the center of almost all human pathologies as well-infectious, autoimmune, metabolic to degenerative. Both hypo and hyper level of estrogen has been linked to chronic and acute diseases. While normal aging is supposed to lower its level, leading to tissue degeneration (bone, muscle, neural etc.), and metabolite imbalance (glucose, lipid etc.), the increment in inflammatory agents in day-to-day life are enhancing the estrogen (or estrogen mimic) level, fueling 'estrogen dominance'. The resultant excess estrogen is inducing an overexpression of estrogen receptors (ERα and ERβ), harming tissues, leading to autoimmune diseases, and neoplasms. The unprecedented escalation in the polycystic ovary syndrome, infertility, breast cancer, ovary cancer, and gynecomastia cases are indicating that this sensitive hormone is getting exacerbated. This critical review is an effort to analyze the dual, and opposing facets of estrogen, via understanding its crosstalk with other hormones, enzymes, metabolites, and drugs. Why estrogen level correction is no trivial task, and how it can be restored to normalcy by a disciplined lifestyle with wise dietary and selective chemical usage choices has been discussed. Overall, our current state of knowledge does not disclose the full picture of estrogen's pleiotropic importance. Hence, this review should be a resource for general public as well as researchers to work in that direction. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas.

    Science.gov (United States)

    Takagi, Mayu; Miki, Yasuhiro; Miyashita, Minoru; Hata, Shuko; Yoda, Tomomi; Hirakawa, Hisashi; Sagara, Yasuaki; Rai, Yoshiaki; Ohi, Yasuyo; Tamaki, Kentaro; Ishida, Takanori; Suzuki, Takashi; Ouchi, Noriaki; Sasano, Hironobu

    2016-02-01

    The great majority of invasive lobular carcinoma (ILC) is estrogen-dependent luminal A type carcinoma but the details of estrogen actions and its intratumoral metabolism have not been well studied compared to invasive ductal carcinoma (IDC). We first immunolocalized estrogen-related enzymes including estrogen sulfotransferase (EST), estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase (HSD) 1/2, and aromatase. We then evaluated the tissue concentrations of estrogens in ILC and IDC and subsequently estrogen-responsive gene profiles in these tumors in order to explore the possible differences and/or similarity of intratumoral estrogen environment of these two breast cancer subtypes. The status of STS and 17βHSD1 was significantly lower in ILCs than IDCs (p = 0.022 and p < 0.0001), but that of EST and 17βHSD2 vice versa (p < 0.0001 and p = 0.0106). In ILCs, tissue concentrations of estrone and estradiol were lower than those in IDCs (p = 0.0709 and 0.069). In addition, the great majority of estrogen response genes tended to be lower in ILCs. Among those genes above, FOXP1 was significantly higher in ILCs than in IDCs (p = 0.002). FOXP1 expression was reported to be significantly higher in relapse-free IDC patients treated with tamoxifen. Therefore, tamoxifen may be considered an option of endocrine therapy for luminal A type ILC patients. This is the first study to demonstrate the detailed and comprehensive status of intratumoral production and metabolism of estrogens and the status of estrogen response genes in luminal A-like ILC with comparison to those in luminal A-like IDCs.

  12. Factors Affecting Distribution of Estrogenicity in the Influents, Effluents, and Biosolids of Canadian Wastewater Treatment Plants.

    Science.gov (United States)

    Shieh, Ben H H; Louie, Alvin; Law, Francis C P

    2016-05-01

    Canadian wastewater treatment plants (WWTPs) release significant amounts of estrogenic chemicals to nearby surface waters. Environmental estrogens have been implicated as the causative agents of many developmental and reproductive problems in animals, including fish. The goals of this study were to assess the estrogenic activity in the influents, effluents, and biosolids of thirteen Canadian WWTPs using the yeast estrogen screen (YES) bioassay and to investigate whether factors, such as wastewater treatment method, sample storage, extraction efficiency, population, and summer/winter temperature had any effects on the distribution of estrogenicity in the WWTPs. Results of the study showed that estrogenicity from the influent to the effluent decreased in seven WWTPs, increased in two WWTPs, and did not change in four WWTPs during the winter. Estrogenic concentrations generally decreased in the order of biosolids > influents > effluents and ranged from 1.57 to 24.6, 1.25E-02 to 3.84E-01, and 9.46E-03 to 3.90E-01 ng estradiol equivalents/g or ml, respectively. The estrogenicity in the final effluents, but not those in the influents and biosolids, was significantly higher in the summer than the winter. Among the WWTP treatment methods, advanced, biological nutrient removal appeared to be the most effective method to remove estrogenic chemicals from wastewaters in Canada. Our studies help to identify factors or mechanisms that affect the distribution of estrogenicity in WWTPs, providing a better understanding on the discharges of estrogenic chemicals from WWTPs.

  13. Estrogen regulation of TRPM8 expression in breast cancer cells

    International Nuclear Information System (INIS)

    Chodon, Dechen; Guilbert, Arnaud; Dhennin-Duthille, Isabelle; Gautier, Mathieu; Telliez, Marie-Sophie; Sevestre, Henri; Ouadid-Ahidouch, Halima

    2010-01-01

    The calcium-permeable cation channel TRPM8 (melastatin-related transient receptor potential member 8) is over-expressed in several cancers. The present study aimed at investigating the expression, function and potential regulation of TRPM8 channels by ER alpha (estrogen receptor alpha) in breast cancer. RT-PCR, Western blot, immuno-histochemical, and siRNA techniques were used to investigate TRPM8 expression, its regulation by estrogen receptors, and its expression in breast tissue. To investigate the channel activity in MCF-7 cells, we used the whole cell patch clamp and the calcium imaging techniques. TRPM8 channels are expressed at both mRNA and protein levels in the breast cancer cell line MCF-7. Bath application of the potent TRPM8 agonist Icilin (20 μM) induced a strong outwardly rectifying current at depolarizing potentials, which is associated with an elevation of cytosolic calcium concentration, consistent with established TRPM8 channel properties. RT-PCR experiments revealed a decrease in TRPM8 mRNA expression following steroid deprivation for 48 and 72 hours. In steroid deprived medium, addition of 17-beta-estradiol (E 2 , 10 nM) increased both TRPM8 mRNA expression and the number of cells which respond to Icilin, but failed to affect the Ca 2+ entry amplitude. Moreover, silencing ERα mRNA expression with small interfering RNA reduced the expression of TRPM8. Immuno-histochemical examination of the expression of TRPM8 channels in human breast tissues revealed an over-expression of TRPM8 in breast adenocarcinomas, which is correlated with estrogen receptor positive (ER + ) status of the tumours. Taken together, these results show that TRPM8 channels are expressed and functional in breast cancer and that their expression is regulated by ER alpha

  14. Cigarette Smoke and Estrogen Signaling in Human Airway Smooth Muscle

    Directory of Open Access Journals (Sweden)

    Venkatachalem Sathish

    2015-06-01

    Full Text Available Aims: Cigarette smoke (CS in active smokers and second-hand smoke exposure exacerbate respiratory disorders such as asthma and chronic bronchitis. While women are known to experience a more asthmatic response to CS than emphysema in men, there is limited information on the mechanisms of CS-induced airway dysfunction. We hypothesize that CS interferes with a normal (protective bronchodilatory role of estrogens, thus worsening airway contractility. Methods: We tested effects of cigarette smoke extract (CSE on 17β-estradiol (E2 signaling in enzymatically-dissociated bronchial airway smooth muscle (ASM obtained from lung samples of non-smoking female patients undergoing thoracic surgery. Results: In fura-2 loaded ASM cells, CSE increased intracellular calcium ([Ca2+]i responses to 10µM histamine. Acute exposure to physiological concentrations of E2 decreased [Ca2+]i responses. However, in 24h exposed CSE cells, although expression of estrogen receptors was increased, the effect of E2 on [Ca2+]i was blunted. Acute E2 exposure also decreased store-operated Ca2+ entry and inhibited stromal interaction molecule 1 (STIM1 phosphorylation: effects blunted by CSE. Acute exposure to E2 increased cAMP, but less so in 24h CSE-exposed cells. 24h CSE exposure increased S-nitrosylation of ERα. Furthermore, 24h CSE-exposed bronchial rings showed increased bronchoconstrictor agonist responses that were not reduced as effectively by E2 compared to non-CSE controls. Conclusion: These data suggest that CS induces dysregulation of estrogen signaling in ASM, which could contribute to increased airway contractility in women exposed to CS.

  15. Estrogens modulate ventrolateral ventromedial hypothalamic glucose-inhibited neurons

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    Ammy M. Santiago

    2016-10-01

    Full Text Available Objective: Brain regulation of glucose homeostasis is sexually dimorphic; however, the impact sex hormones have on specific neuronal populations within the ventromedial hypothalamic nucleus (VMN, a metabolically sensitive brain region, has yet to be fully characterized. Glucose-excited (GE and -inhibited (GI neurons are located throughout the VMN and may play a critical role in glucose and energy homeostasis. Within the ventrolateral portion of the VMN (VL-VMN, glucose sensing neurons and estrogen receptor (ER distributions overlap. We therefore tested the hypothesis that VL-VMN glucose sensing neurons were sexually dimorphic and regulated by 17β-estradiol (17βE. Methods: Electrophysiological recordings of VL-VMN glucose sensing neurons in brain slices isolated from age- and weight-matched female and male mice were performed in the presence and absence of 17βE. Results: We found a new class of VL-VMN GI neurons whose response to low glucose was transient despite continued exposure to low glucose. Heretofore, we refer to these newly identified VL-VMN GI neurons as ‘adapting’ or AdGI neurons. We found a sexual dimorphic response to low glucose, with male nonadapting GI neurons, but not AdGI neurons, responding more robustly to low glucose than those from females. 17βE blunted the response of both nonadapting GI and AdGI neurons to low glucose in both males and females, which was mediated by activation of estrogen receptor β and inhibition of AMP-activated kinase. In contrast, 17βE had no impact on GE or non-glucose sensing neurons in either sex. Conclusion: These data suggest sex differences and estrogenic regulation of VMN hypothalamic glucose sensing may contribute to the sexual dimorphism in glucose homeostasis. Author Video: Author Video Watch what authors say about their articles Keywords: 17β-estradiol, AMP-activated kinase, Glucose excited neurons, Glucose inhibited neurons, Ventromedial hypothalamic nucleus, Sexual dimorphism

  16. Protection of estrogen in portal hypertension gastropathy: an experimental model

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    Maria Isabel Morgan-Martins

    2011-09-01

    Full Text Available CONTEXT: Portal hypertension is a complication secondary to cirrhosis that is characterized by increased blood flow and/or vascular resistance in the portal system, causing the appearance of a hyperdynamic collateral circulation. Partial portal vein ligation is an experimental model used in rats to study the pathophysiological mechanisms involved in pre-hepatic portal hypertension. Estrogen E2 is an antioxidant molecule with various physiological actions. OBJECTIVES: To evaluate the antioxidant activity of endogenous estrogen in an experimental model of partial portal vein ligation by comparing intact with castrated rats. METHODS: Twenty Wistar rats, weighing on average 250 g were used and divided into four groups: sham-operated (SO; intact (I with partial portal vein ligation (I + PPVL, castrated (C and castrated with partial ligation of the vein (C + PPVL. Day 1: castration or sham-operation; day 7, PPVL surgery; on day 15 post-PPVL, portal pressure in the mesenteric vein of rats was measured on polygraph Letica. Lipid peroxidation in the stomach was assessed using the technique of thiobarbituric acid reactive substances and activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. Statistical analysis was done with ANOVA - Student-Newman-Keuls (mean ± SE, and P<0.05 was considered as significant. RESULTS: Portal pressure was significantly increased in C + PPVL as compared to the other groups. There was no significant difference in the group of intact rats. TBARS showed significant damage in C and C + PPVL in relation to others. Antioxidant enzymes were significantly increased in the castrated rats with subsequent PPVL as compared to the other groups. CONCLUSION: We suggest that estrogen E2 plays a protective role in intact compared with castrated rats because it presents hydrophenolic radicals in its molecule, thus acting as an antioxidant in this experimental model.

  17. Protection of estrogen in portal hypertension gastropathy: an experimental model.

    Science.gov (United States)

    Morgan-Martins, Maria Isabel; Jacques, Simone Iahnig; Hartmann, Renata Minuzzo; Marques, Camila Moraes; Marroni, Cláudio Augusto; Marroni, Norma Possa

    2011-01-01

    Portal hypertension is a complication secondary to cirrhosis that is characterized by increased blood flow and/or vascular resistance in the portal system, causing the appearance of a hyperdynamic collateral circulation. Partial portal vein ligation is an experimental model used in rats to study the pathophysiological mechanisms involved in pre-hepatic portal hypertension. Estrogen E2 is an antioxidant molecule with various physiological actions. To evaluate the antioxidant activity of endogenous estrogen in an experimental model of partial portal vein ligation by comparing intact with castrated rats. Twenty Wistar rats, weighing on average 250 g were used and divided into four groups: sham-operated (SO); intact (I) with partial portal vein ligation (I + PPVL), castrated (C) and castrated with partial ligation of the vein (C + PPVL). Day 1: castration or sham-operation; day 7, PPVL surgery; on day 15 post-PPVL, portal pressure in the mesenteric vein of rats was measured on polygraph Letica. Lipid peroxidation in the stomach was assessed using the technique of thiobarbituric acid reactive substances and activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. Statistical analysis was done with ANOVA - Student-Newman-Keuls (mean ± SE), and P<0.05 was considered as significant. Portal pressure was significantly increased in C + PPVL as compared to the other groups. There was no significant difference in the group of intact rats. TBARS showed significant damage in C and C + PPVL in relation to others. Antioxidant enzymes were significantly increased in the castrated rats with subsequent PPVL as compared to the other groups. We suggest that estrogen E2 plays a protective role in intact compared with castrated rats because it presents hydrophenolic radicals in its molecule, thus acting as an antioxidant in this experimental model.

  18. The selective estrogen receptor modulators in breast cancer prevention.

    Science.gov (United States)

    Li, Fangxuan; Dou, Jinli; Wei, Lijuan; Li, Shixia; Liu, Juntian

    2016-05-01

    Persistently increased blood levels of estrogens are associated with an increased risk of breast cancer. Selective estrogen receptor modulators (SERMs) are a class of compounds that act on the estrogen receptor (ER). Several clinical trials have demonstrated the effectiveness of its prophylactic administration. Incidence of invasive ER-positive breast cancer was reduced by SERMs treatment, especially for those women with high risk of developing breast cancer. In this study, we reviewed the clinical application of SERMs in breast cancer prevention. To date, four prospective randomized clinical trials had been performed to test the efficacy of tamoxifen for this purpose. Concerning on the benefit and cost of tamoxifen, various studies from different countries demonstrated that chemoprevention with tamoxifen seemed to be cost-effective for women with a high risk of invasive breast cancer. Based above, tamoxifen was approved for breast cancer prevention by the US Food and Drug Administration in 1998. Raloxifene was also approved for postmenopausal women in 2007 for breast cancer prevention which reduces the risk of invasive breast cancer with a lower risk of unwanted stimulation of endometrium. Thus, raloxifene is considered to have a better clinical possesses as prophylactic agent. Several other agents, such as arzoxifene and lasofoxifene, are currently being investigated in clinic. The American Society of Clinical Oncology and National Comprehensive Cancer Network had published guidelines on breast cancer chemoprevention by SERMs. However, use of tamoxifen and raloxifene for primary breast cancer prevention was still low. A broader educational effort is needed to alert women and primary care physicians that SERMs are available to reduce breast cancer risk.

  19. The ventromedial hypothalamus oxytocin induces locomotor behavior regulated by estrogen.

    Science.gov (United States)

    Narita, Kazumi; Murata, Takuya; Matsuoka, Satoshi

    2016-10-01

    Our previous studies demonstrated that excitation of neurons in the rat ventromedial hypothalamus (VMH) induced locomotor activity. An oxytocin receptor (Oxtr) exists in the VMH and plays a role in regulating sexual behavior. However, the role of Oxtr in the VMH in locomotor activity is not clear. In this study we examined the roles of oxytocin in the VMH in running behavior, and also investigated the involvement of estrogen in this behavioral change. Microinjection of oxytocin into the VMH induced a dose-dependent increase in the running behavior in male rats. The oxytocin-induced running activity was inhibited by simultaneous injection of Oxtr-antagonist, (d(CH2)5(1), Try(Me)(2), Orn(8))-oxytocin. Oxytocin injection also induced running behavior in ovariectomized (OVX) female rats. Pretreatment of the OVX rats with estrogen augmented the oxytocin-induced running activity twofold, and increased the Oxtr mRNA in the VMH threefold. During the estrus cycle locomotor activity spontaneously increased in the dark period of proestrus. The Oxtr mRNA was up-regulated in the proestrus afternoon. Blockade of oxytocin neurotransmission by its antagonist before the onset of the dark period of proestrus decreased the following nocturnal locomotor activity. These findings demonstrate that Oxtr in the VMH is involved in the induction of running behavior and that estrogen facilitates this effect by means of Oxtr up-regulation, suggesting the involvement of oxytocin in the locomotor activity of proestrus female rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Effect of Estrogen and Progeterone on seed germination

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    Nirmala

    Full Text Available Early pregnancy detection in dairy cattle is an integral part of a successful animal husbandry practice. A simple seed germination technique (Punyakoti test comprises observation of differential seed germination response of wheat seeds to diluted fresh urine samples as reflected by significant inhibition of germination percentage in pregnant cow urine when compared to non pregnant cow urine. Hormone metabolites excreted through urine might affect the seed germination in pregnant cow urine. In the present study an attempt was made to test the effect of hormones (in their natural forms at different concentrations of estrogen (17-ß estradiol and progesterone on wheat and green gram germination. Stock solutions of estrogen and progesterone were prepared in alcohol (1mg/ml and serial dilutions made using distilled water to get the concentrations of T1=10, T2=1, T3=0.1 and T4=0.01 μg/ml respectively in treatment groups. About 15 seeds each of wheat and green gram were taken in sterile Petri dishes into which 15ml of each test preparation was poured. The treatments were compared with distilled water and alcohol controls. The study was conducted for a period of five days during which seed germination was observed after 48 hrs and shoot lengths were also measured by the end of study. The average seed germination and shoot length in treatment groups did not vary significantly (P>0.05 when compared with that of control groups. Thus from the present study, it can be concluded that estrogen and progesterone in their natural form will not affect seed germination and shoot length. [Veterinary World 2008; 1(8.000: 241-242

  1. Inter-laboratory exercise on steroid estrogens in aqueous samples

    DEFF Research Database (Denmark)

    Heath, E.; Kosjek, T.; Andersen, Henrik Rasmus

    2010-01-01

    to the analytical techniques applied, the accuracy and reproducibility of the analytical methods and the nature of the sample matrices. Overall, the results obtained in this inter-laboratory exercise reveal a high level of competence among the participating laboratories for the detection of steroid estrogens......An inter-laboratory comparison exercise was organized among European laboratories, under the aegis of EU COST Action 636: "Xenobiotics in Urban Water Cycle" The objective was to evaluate the performance of testing laboratories determining "Endocrine Disrupting Compounds" (EDC) in various aqueous...

  2. The estrogen-related receptors and the adipocyte.

    Science.gov (United States)

    Carnesecchi, Julie; Vanacker, Jean-Marc

    2013-08-01

    The estrogen-related receptors (ERRα, β, and γ) are orphan members of the nuclear receptor superfamily. ERRα and γ are highly expressed in tissues displaying elevated energy demands and are involved in several aspects of energetic metabolism, which they regulate mostly in association with members of the PGC-1 coactivator family. These activities have mostly been documented in the liver, heart, or skeletal muscle. ERRα and γ are also highly expressed in adipocytes. Their precise roles in this cell type are less documented, although published data indicate that they contribute to cell differentiation as well as functionality. This review describes these activities.

  3. Ligands specify estrogen receptor alpha nuclear localization and degradation

    Directory of Open Access Journals (Sweden)

    Caze-Subra Stéphanie

    2010-12-01

    Full Text Available Abstract Background The estrogen receptor alpha (ERα is found predominately in the nucleus, both in hormone stimulated and untreated cells. Intracellular distribution of the ERα changes in the presence of agonists but the impact of different antiestrogens on the fate of ERα is a matter of debate. Results A MCF-7 cell line stably expressing GFP-tagged human ERα (SK19 cell line was created to examine the localization of ligand-bound GFP-ERα. We combined digitonin-based cell fractionation analyses with fluorescence and immuno-electron microscopy to determine the intracellular distribution of ligand-bound ERα and/or GFP-ERα. Using fluorescence- and electron microscopy we demonstrate that both endogenous ERα and GFP-ERα form numerous nuclear focal accumulations upon addition of agonist, 17β-estradiol (E2, and pure antagonists (selective estrogen regulator disruptor; SERD, ICI 182,780 or RU58,668, while in the presence of partial antagonists (selective estrogen regulator modulator; SERM, 4-hydroxytamoxifen (OHT or RU39,411, diffuse nuclear staining persisted. Digitonin based cell fractionation analyses confirmed that endogenous ERα and GFP-ERα predominantly reside in the nuclear fraction. Overall ERα protein levels were reduced after estradiol treatment. In the presence of SERMs ERα was stabilized in the nuclear soluble fraction, while in the presence of SERDs protein levels decreased drastically and the remaining ERα was largely found in a nuclear insoluble fraction. mRNA levels of ESR1 were reduced compared to untreated cells in the presence of all ligands tested, including E2. E2 and SERDs induced ERα degradation occurred in distinct nuclear foci composed of ERα and the proteasome providing a simple explanation for ERα sequestration in the nucleus. Conclusions Our results indicate that chemical structure of ligands directly affect the nuclear fate and protein turnover of the estrogen receptor alpha independently of their impact on

  4. Effect of estrogens on urinary 15N balance in girls

    International Nuclear Information System (INIS)

    Zachmann, M.; Kempken, B.; Prader, A.

    1984-01-01

    While the anabolic and growth-promoting effects of testosterone are known to be important for pubertal growth in boys, the role of estrogens (E) in the female spurt is less certain. Adrenal androgens have been considered to be more important than ovarian E. To study the anabolic effects of E, there has been carried out a pilot study in 9 girls aged 11 to 15 years. Before and 6 days after the start of E treatment, urinary 15 N balance studies were performed, using 15 NH 4 Cl. (author)

  5. Estrogens regulate the hepatic effects of growth hormone, a hormonal interplay with multiple fates

    DEFF Research Database (Denmark)

    Fernández-Pérez, Leandro; Guerra, Borja; Díaz-Chico, Juan C

    2013-01-01

    The liver responds to estrogens and growth hormone (GH) which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk...

  6. Comparison of short-term estrogenicity tests for identification of hormone-disrupting chemicals

    DEFF Research Database (Denmark)

    Andersen, H R; Andersson, A M; Arnold, S F

    1999-01-01

    induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n...

  7. Dissolved organic carbon from sewage sludge and manure can affect estrogen sorption and mineralization in soils

    Energy Technology Data Exchange (ETDEWEB)

    Stumpe, Britta, E-mail: britta.stumpe@rub.d [Ruhr-University Bochum, Institute of Geography, Department Soil Science/Soil Ecology, Universitaetsstr. 150, 44780 Bochum (Germany); Marschner, Bernd, E-mail: bernd.marschner@rub.d [Ruhr-University Bochum, Institute of Geography, Department Soil Science/Soil Ecology, Universitaetsstr. 150, 44780 Bochum (Germany)

    2010-01-15

    In this study, effects of sewage sludge and manure borne dissolved organic carbon (DOC) on 17beta-estradiol (E2) and 17alpha-ethinylestradiol (EE2) sorption and mineralization processes were investigated in three agricultural soils. Batch equilibrium techniques and equilibrium dialysis methods were used to determine sorption mechanisms between DOC, estrogens and the soil solid phase. It was found that that the presence of organic waste borne DOC decreased estrogen sorption in soils which seems to be controlled by DOC/estrogen complexes in solution and by exchange processes between organic waste derived and soil borne DOC. Incubation studies performed with {sup 14}C-estrogens showed that DOC addition decreased estrogen mineralization, probably due to reduced bioavailability of estrogens associated with DOC. This increased persistence combined with higher mobility could increase the risk of estrogen transport to ground and surface waters. - The effect of DOC on estrogen sorption and mineralization is influenced by exchange processes between organic waste borne and soil derived DOC.

  8. Vaginal estrogen: a dual-edged sword in postoperative healing of the vaginal wall.

    Science.gov (United States)

    Ripperda, Christopher M; Maldonado, Pedro Antonio; Acevedo, Jesus F; Keller, Patrick W; Akgul, Yucel; Shelton, John M; Word, Ruth Ann

    2017-07-01

    Reconstructive surgery for pelvic organ prolapse is plagued with high failure rates possibly due to impaired healing or regeneration of the vaginal wall. Here, we tested the hypothesis that postoperative administration of local estrogen, direct injection of mesenchymal stem cells (MSCs), or both lead to improved wound healing of the injured vagina in a menopausal rat model. Ovariectomized rats underwent surgical injury to the posterior vaginal wall and were randomized to treatment with placebo (n = 41), estrogen cream (n = 47), direct injection of MSCs (n = 39), or both (n = 43). MSCs did not survive after injection and had no appreciable effects on healing of the vaginal wall. Acute postoperative administration of vaginal estrogen altered the response of the vaginal wall to injury with decreased stiffness, decreased collagen content, and decreased expression of transcripts for matrix components in the stromal compartment. Conversely, vaginal estrogen resulted in marked proliferation of the epithelial layer and increased expression of genes related to epithelial barrier function and protease inhibition. Transcripts for genes involved in chronic inflammation and adaptive immunity were also down-regulated in the estrogenized epithelium. Collectively, these data indicate that, in contrast to the reported positive effects of preoperative estrogen on the uninjured vagina, acute administration of postoperative vaginal estrogen has adverse effects on the early phase of healing of the stromal layer. In contrast, postoperative estrogen plays a positive role in healing of the vaginal epithelium after injury.

  9. Fertility of Tall Girls Treated with High-Dose Estrogen, a Dose-Response Relationship

    NARCIS (Netherlands)

    Hendriks, A. E. J.; Drop, S. L. S.; Laven, J. S. E.; Boot, A. M.

    Context: High-dose estrogen treatment to reduce final height of tall girls increases their risk for infertility in later life. Objective: The aim was to study the effect of estrogen dose on fertility outcome of these women. Design/Setting: We conducted a retrospective cohort study of university

  10. Comprehensive assessment of hormones, phytoestrogens, and estrogenic activity in an anaerobic swine waste lagoon

    Science.gov (United States)

    Yost, Erin E.; Meyer, Michael T.; Dietze, Julie E.; Meissner, Benjamin M.; Williams, Mike; Worley-Davis, Lynn; Lee, Boknam; Kullman, Seth W.

    2013-01-01

    In this study, the distribution of steroid hormones, phytoestrogens, and estrogenic activity was thoroughly characterized within the anaerobic waste lagoon of a typical commercial swine sow operation. Three independent rounds of sampling were conducted in June 2009, April 2010, and February 2011. Thirty-seven analytes in lagoon slurry and sludge were assessed using LC/MS-MS, and yeast estrogen screen was used to determine estrogenic activity. Of the hormone analytes, steroidal estrogens were more abundant than androgens or progesterone, with estrone being the predominant estrogen species. Conjugated hormones were detected only at low levels. The isoflavone metabolite equol was by far the predominant phytoestrogen species, with daidzein, genistein, formononetin, and coumestrol present at lower levels. Phytoestrogens were often more abundant than steroidal estrogens, but contributed minimally towards total estrogenic activity. Analytes were significantly elevated in the solid phases of the lagoon; although low observed log KOC values suggest enhanced solubility in the aqueous phase, perhaps due to dissolved or colloidal organic carbon. The association with the solid phase, as well as recalcitrance of analytes to anaerobic degradation, results in a markedly elevated load of analytes and estrogenic activity within lagoon sludge. Overall, findings emphasize the importance of adsorption and transformation processes in governing the fate of these compounds in lagoon waste, which is ultimately used for broadcast application as a fertilizer.

  11. Identifying a Mechanism for Crosstalk Between the Estrogen and Glucocorticoid Receptors | Center for Cancer Research

    Science.gov (United States)

    Estrogen has long been known to play important roles in the development and progression of breast cancer. Its receptor (ER), a member of the steroid receptor family, binds to estrogen response elements (EREs) in DNA and regulates gene transcription. More recently, another steroid receptor family member, the glucocorticoid receptor (GR), has been implicated in breast cancer

  12. Dissolved organic carbon from sewage sludge and manure can affect estrogen sorption and mineralization in soils

    International Nuclear Information System (INIS)

    Stumpe, Britta; Marschner, Bernd

    2010-01-01

    In this study, effects of sewage sludge and manure borne dissolved organic carbon (DOC) on 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) sorption and mineralization processes were investigated in three agricultural soils. Batch equilibrium techniques and equilibrium dialysis methods were used to determine sorption mechanisms between DOC, estrogens and the soil solid phase. It was found that that the presence of organic waste borne DOC decreased estrogen sorption in soils which seems to be controlled by DOC/estrogen complexes in solution and by exchange processes between organic waste derived and soil borne DOC. Incubation studies performed with 14 C-estrogens showed that DOC addition decreased estrogen mineralization, probably due to reduced bioavailability of estrogens associated with DOC. This increased persistence combined with higher mobility could increase the risk of estrogen transport to ground and surface waters. - The effect of DOC on estrogen sorption and mineralization is influenced by exchange processes between organic waste borne and soil derived DOC.

  13. The relationship between ovarian steroids and uterine estrogen receptors during late pregnancy

    International Nuclear Information System (INIS)

    Cathey, T.M.; Chung, Kyung W.

    1991-01-01

    Although a direct interdependence exists between the ovarian steroids, estrogen and progesterone, the exact role of these two hormones during pregnancy, especially late pregnancy, is not completely understood. Investigations have been conducted to determine whether the circulating levels of progesterone and estrogen or changes in the ratio of progesterone/estrogen in relation to the concentration of uterine estrogen receptors are associated with triggering parturition. Ninety-day old female rats were sacrificed at gestation days 14, 16, 18, 20 and two days post-partum. The plasma levels of estradiol and progesterone were measured by solid-phase radioimmunoassay. Uterine cytosol was subjected to a charcoal binding assay to determine the concentration of estrogen receptors. Our findings demonstrate that there is a significant drop in both plasma progesterone and estradiol during late pregnancy. Also indicated is a significant increase in uterine estrogen receptors throughout late pregnancy. Finally, during this period there is a direct correlation between the shift in the progesterone/estrogen ratio and the increase in the concentration of uterine estrogen receptors in late pregnancy

  14. Use of vitellogenin as a biomarker for estrogenic effect: What is the baseline?

    DEFF Research Database (Denmark)

    Bjerregaard, Poul; Holbech, Henrik; Pedersen, Knud Ladegaard

    investigated in 2004 were revisited in the 2010 study and vitellogenin concentrations had decreased. Between 2004 and 2010 some discharges (via septic tanks) from scattered houses in the open land known to discharge estrogenic activity had been removed and this may have reduced the addition of estrogenicity...

  15. Modulatory effect of raloxifene and estrogen on the metabolic action of growth hormone in hypopituitary women.

    LENUS (Irish Health Repository)

    Birzniece, Vita

    2010-05-01

    The metabolic action of GH is attenuated by estrogens administered via the oral route. Selective estrogen receptor modulators lower IGF-I to a lesser degree than 17beta-estradiol in GH-deficient women, and their effect on fat and protein metabolism is unknown.

  16. Estrogen receptor-alpha-immunoreactive neurons in the periaqueductal gray of the adult ovariectomized female cat

    NARCIS (Netherlands)

    VanderHorst, Veronique G.J.M.; Meijer, Ellie; Schasfoort, Fabienne C.; Leeuwen, Fred van; Holstege, Gert

    1998-01-01

    Anatomical and physiological studies in rodent and cat have shown that distinct parts of the midbrain periaqueductal gray (FAG) are important for the estrogen dependent, female reproductive behavior. The present study gives a detailed overview of the estrogen receptor-alpha-immunoreactive (ER-IR)

  17. Estrogen and progesterone stimulate Schwann cell proliferation in a sex- and age-dependent manner

    DEFF Research Database (Denmark)

    Svenningsen, Åsa Fex; Kanje, M

    1999-01-01

    The effects of estrogen and progesterone on Schwann cell proliferation were studied in cultured segments of the rat sciatic nerve from adult male, female, and newborn rats, by measurement of [3H thymidine incorporation or bromo-deoxy-uridine- (BrdU)-labelling and immunocytochemistry. Estrogen (10...

  18. The relationship between ovarian steroids and uterine estrogen receptors during late pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Cathey, T.M.; Chung, Kyung W. (Univ. of Oklahoma, Oklahoma City (USA))

    1991-01-01

    Although a direct interdependence exists between the ovarian steroids, estrogen and progesterone, the exact role of these two hormones during pregnancy, especially late pregnancy, is not completely understood. Investigations have been conducted to determine whether the circulating levels of progesterone and estrogen or changes in the ratio of progesterone/estrogen in relation to the concentration of uterine estrogen receptors are associated with triggering parturition. Ninety-day old female rats were sacrificed at gestation days 14, 16, 18, 20 and two days post-partum. The plasma levels of estradiol and progesterone were measured by solid-phase radioimmunoassay. Uterine cytosol was subjected to a charcoal binding assay to determine the concentration of estrogen receptors. Our findings demonstrate that there is a significant drop in both plasma progesterone and estradiol during late pregnancy. Also indicated is a significant increase in uterine estrogen receptors throughout late pregnancy. Finally, during this period there is a direct correlation between the shift in the progesterone/estrogen ratio and the increase in the concentration of uterine estrogen receptors in late pregnancy.

  19. Variations in estrogen receptor ? gene and risk of dementia, and brain volumes on MRI.

    NARCIS (Netherlands)

    S.C.E. Schuit (Stephanie); A. Hofman (Albert); P.J. Koudstaal (Peter Jan); C.M. van Duijn (Cornelia); A.G. Uitterlinden (André); H.A.P. Pols (Huib); M.M.B. Breteler (Monique); J.B.J. van Meurs (Joyce); T. den Heijer (Tom)

    2004-01-01

    textabstractThe role of estrogens in Alzheimer's disease (AD) is controversial. We investigated the association between well-recognized, and potentially functional, polymorphisms in the estrogen receptor (ER) gene and the risk of AD in a prospective study of 6056 Caucasian older men and women aged

  20. YEAST ESTROGEN SCREEN FOR EXAMINING THE RELATIVE EXPOSURE OF CELLS TO NATURAL AND XENOESTROGENS

    Science.gov (United States)

    Xenoestrogens, such as o,p'-DDT and octyl phenol (OP) have been associated with reproductive abnormalities in various wildlife species. Xenoestrogens mimic the natural estrogen 17b-estradiol and compete for binding to the estrogen receptor. Even though the affinity of o,p'-DDTan...

  1. Musculoskeletal Complications and Bone Metastases in Breast Cancer Patients Undergoing Estrogen Deprivation Therapy

    Science.gov (United States)

    2016-10-01

    tissue (MAT) in estrogen deficient mice. Epidemiological studies have demonstrated a strong link between obesity and increased breast cancer...the accrual of MAT is dramatically accelerated with obesity , estrogen deprivation, glucocorticoid use, chemotherapy, and radiation therapy...Tucson, AZ 2005 – 2006 Graduate Research Assistant, McKnight Brain Institute, Neural Systems, Memory and Aging (NSMA), Department of Psychology

  2. Integration of Nuclear- and Extranuclear-Initiated Estrogen Receptor Signaling in Breast Cancer Cells

    Science.gov (United States)

    Madak Erdogan, Zeynep

    2009-01-01

    Estrogenic hormones exert their effects through binding to Estrogen Receptors (ERs), which work in concert with coregulators and extranuclear signaling pathways to control gene expression in normal as well as cancerous states, including breast tumors. In this thesis, we have used multiple genome-wide analysis tools to elucidate various ways that…

  3. Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals

    DEFF Research Database (Denmark)

    Andersen, Helle Raun; Andersson, Anna-Maria; Arnold, Steven F.

    1999-01-01

    The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, est...

  4. Comparison of short-term estrogenicity tests for identification of hormone-disrupting chemicals

    DEFF Research Database (Denmark)

    Andersen, H R; Andersson, A M; Arnold, S F

    1999-01-01

    The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, est...

  5. Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice

    Science.gov (United States)

    Binge eating afflicts approximately 5% of US adults, though effective treatments are limited. Here, we showed that estrogen replacement substantially suppresses binge-like eating behavior in ovariectomized female mice. Estrogen-dependent inhibition of binge-like eating was blocked in female mice spe...

  6. Phytoestrogens and Mycoestrogens Induce Signature Structure Dynamics Changes on Estrogen Receptor α

    Directory of Open Access Journals (Sweden)

    Xueyan Chen

    2016-08-01

    Full Text Available Endocrine disrupters include a broad spectrum of chemicals such as industrial chemicals, natural estrogens and androgens, synthetic estrogens and androgens. Phytoestrogens are widely present in diet and food supplements; mycoestrogens are frequently found in grains. As human beings and animals are commonly exposed to phytoestrogens and mycoestrogens in diet and environment, it is important to understand the potential beneficial or hazardous effects of estrogenic compounds. Many bioassays have been established to study the binding of estrogenic compounds with estrogen receptor (ER and provided rich data in the literature. However, limited assays can offer structure information with regard to the ligand/ER complex. Our current study surveys the global structure dynamics changes for ERα ligand binding domain (LBD when phytoestrogens and mycoestrogens bind. The assay is based on the structure dynamics information probed by hydrogen deuterium exchange mass spectrometry and offers a unique viewpoint to elucidate the mechanism how phytoestrogens and mycoestrogens interact with estrogen receptor. The cluster analysis based on the hydrogen deuterium exchange (HDX assay data reveals a unique pattern when phytoestrogens and mycoestrogens bind with ERα LBD compared to that of estradiol and synthetic estrogen modulators. Our study highlights that structure dynamics could play an important role in the structure function relationship when endocrine disrupters interact with estrogen receptors.

  7. The Influence of Estrogens on the Biological and Therapeutic Actions of Growth Hormone in the Liver

    Directory of Open Access Journals (Sweden)

    Leandro Fernández-Pérez

    2012-07-01

    Full Text Available GH is main regulator of body growth and composition, somatic development, intermediate metabolism and gender-dependent dimorphism in mammals. The liver is a direct target of estrogens because it expresses estrogen receptors which are connected with development, lipid metabolism and insulin sensitivity, hepatic carcinogenesis, protection from drug-induced toxicity and fertility. In addition, estrogens can modulate GH actions in liver by acting centrally, regulating pituitary GH secretion, and, peripherally, by modulating GHR-JAK2-STAT5 signalling pathway. Therefore, the interactions of estrogens with GH actions in liver are biologically and clinically relevant because disruption of GH signaling may cause alterations of its endocrine, metabolic, and gender differentiated functions and it could be linked to dramatic impact in liver physiology during development as well as in adulthood. Finally, the interplay of estrogens with GH is relevant because physiological roles these hormones have in human, and the widespread exposition of estrogen or estrogen-related compounds in human. This review highlights the importance of these hormones in liver physiology as well as how estrogens modulate GH actions in liver which will help to improve the clinical use of these hormones.

  8. Expression of aromatase and estrogen receptor alpha in chondrosarcoma, but no beneficial effect of inhibiting estrogen signaling both in vitro and in vivo

    NARCIS (Netherlands)

    Meijer, D.; Gelderblom, Hans; Karperien, Hermanus Bernardus Johannes; Cleton-Jansen, A.M.; Hogendoorn, C.W.; Bovee, J.

    2011-01-01

    Background: Chondrosarcomas are malignant cartilage-forming tumors which are highly resistant to conventional chemotherapy and radiotherapy. Estrogen signaling is known to play an important role in proliferation and differentiation of chondrocytes and in growth plate regulation at puberty. Our

  9. Discovery of estrogen receptor α modulators from natural compounds in Si-Wu-Tang series decoctions using estrogen-responsive MCF-7 breast cancer cells.

    Science.gov (United States)

    Liu, Li; Ma, Hongyue; Tang, Yuping; Chen, Wenxing; Lu, Yin; Guo, Jianming; Duan, Jin-Ao

    2012-01-01

    The binding between the estrogen receptor α (ER-α) and a variety of compounds in traditional Chinese formulae, Si-Wu-Tang (SWT) series decoctions, was studied using a stably-transfected human breast cancer cell line (MVLN). In 38 compounds tested from SWT series decoctions, the estrogen-like activity of 22 compounds was above 60% in 20 μg mL(-1). Furthermore, theoretical affinity of these compounds was certificated using the functional virtual screen of ER-α modulators by FlexX-Pharm. The accuracy of functional virtual screening of ER-α modulators could reach to 77.27%. The results showed that some compounds, such as organic acids and flavones in SWT series decoctions could be used as selective estrogen receptor modulators (SERMs) and could be selected for further development as potential agents for estrogen related diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Detecting estrogenic activity in water samples withestrogen-sensitive yeast cells using spectrophotometry and fluorescencemicroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Wozei, E.; Holman, H-Y.N.; Hermanowicz, S.W.; Borglin S.

    2006-03-15

    Environmental estrogens are environmental contaminants that can mimic the biological activities of the female hormone estrogen in the endocrine system, i.e. they act as endocrine disrupters. Several substances are reported to have estrogen-like activity or estrogenic activity. These include steroid hormones, synthetic estrogens (xenoestrogens), environmental pollutants and phytoestrogens (plant estrogens). Using the chromogenic substrate ortho-nitrophenyl-{beta}-D-galactopyranoside (ONPG) we show that an estrogen-sensitive yeast strain RMY/ER-ERE, with human estrogen receptor (hER{alpha}) gene and the lacZ gene which encodes the enzyme {beta}-galactosidase, is able to detect estrogenic activity in water samples over a wide range of spiked concentrations of the hormonal estrogen 17{beta}-estradiol (E2). Ortho-nitrophenol (ONP), the yellow product of this assay can be detected using spectrophotometry but requires cell lysis to release the enzyme and allow product formation. We improved this aspect in a fluorogenic assay by using fluorescein di-{beta}-D-galactopyranoside (FDG) as a substrate. The product was visualized using fluorescence microscopy without the need to kill, fix or lyse the cells. We show that in live yeast cells, the uptake of E2 and the subsequent production of {beta}-galactosidase enzyme occur quite rapidly, with maximum enzyme-catalyzed fluorescent product formation evident after about 30 minutes of exposure to E2. The fluorogenic assay was applied to a selection of estrogenic compounds and the Synchrotron-based Fourier transform infrared (SR-FTIR) spectra of the cells obtained to better understand the yeast whole cell response to the compounds. The fluorogenic assay is most sensitive to E2, but the SR-FTIR spectra suggest that the cells respond to all the estrogenic compounds tested even when no fluorescent response was detected. These findings are promising and may shorten the duration of environmental water screening and monitoring regimes using

  11. Pharmacology of conjugated equine estrogens: efficacy, safety and mechanism of action.

    Science.gov (United States)

    Bhavnani, Bhagu R; Stanczyk, Frank Z

    2014-07-01

    Oral conjugated equine estrogens (CEE) are the most used estrogen formulation for postmenopausal hormone therapy either alone or in combination with a progestin. CEE is most commonly used for the management of early menopausal symptoms such as hot flashes, vaginitis, insomnia, and mood disturbances. Additionally, if used at the start of the menopausal phase (age 50-59 years), CEE prevents osteoporosis and may in some women reduce the risk of cardiovascular disease (CVD) and Alzheimer's disease (AD). There appears to be a common mechanism through which estrogens can protect against CVD and AD. CEE is a natural formulation of an extract prepared from pregnant mares' urine. The product monogram lists the presence of only 10 estrogens consisting of the classical estrogens, estrone and 17β-estradiol, and a group of unique ring B unsaturated estrogens such as equilin and equilenin. The ring B unsaturated estrogens are formed by an alternate steroidogenic pathway in which cholesterol is not an obligatory intermediate. Both the route of administration and structure of these estrogens play a role in the overall pharmacology of CEE. In contrast to 17β-estradiol, ring B unsaturated estrogens express their biological effects mainly mediated by the estrogen receptor β and not the estrogen receptor α. All estrogen components of CEE are antioxidants, and some ring B unsaturated estrogens have several fold greater antioxidant activity than estrone and 17β-estradiol. The cardioprotective and neuroprotective effects of CEE appear to be, to some extent, due to its ability to prevent the formation of oxidized LDL and HDL, and by inhibiting or modulating some of the key proteases involved in programmed cell death (apoptosis) induced by the excess neurotransmitter glutamate and other neurotoxins. Selective combinations of ring B unsaturated estrogens have the potential of being developed as novel therapeutic agents for the prevention of cardiovascular disease and Alzheimer

  12. Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

    Directory of Open Access Journals (Sweden)

    Watson Cheryl S

    2010-10-01

    Full Text Available Abstract Background Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens. Methods We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone at 10 pM (representing pre-development levels, and 1 nM (representing higher cycle-dependent and pregnancy levels in combinations with the same levels of xenoestrogens in GH3/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2 phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively. Results All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses. Conclusions Responses mediated by endogenous estrogens representing different life stages are

  13. Endocrine disruptive estrogens role in electron transfer: bio-electrochemical remediation with microbial mediated electrogenesis.

    Science.gov (United States)

    Kumar, A Kiran; Reddy, M Venkateswar; Chandrasekhar, K; Srikanth, S; Mohan, S Venkata

    2012-01-01

    Bioremediation of selected endocrine disrupting compounds (EDCs)/estrogens viz. estriol (E3) and ethynylestradiol (EE2) was evaluated in bio-electrochemical treatment (BET) system with simultaneous power generation. Estrogens supplementation along with wastewater documented enhanced electrogenic activity indicating their function in electron transfer between biocatalyst and anode as electron shuttler. EE2 addition showed more positive impact on the electrogenic activity compared to E3 supplementation. Higher estrogen concentration showed inhibitory effect on the BET performance. Poising potential during start up phase showed a marginal influence on the power output. The electrons generated during substrate degradation might have been utilized for the EDCs break down. Fuel cell behavior and anodic oxidation potential supported the observed electrogenic activity with the function of estrogens removal. Voltammetric profiles, dehydrogenase and phosphatase enzyme activities were also found to be in agreement with the power generation, electron discharge and estrogens removal. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Structures and the Hydrogen Bonding Abilities of Estrogens Studied by Supersonic Jet/laser Spectroscopy

    Science.gov (United States)

    Morishima, Fumiya; Inokuchi, Yoshiya; Ebata, Takayuki

    2013-06-01

    Estrone, estradiol, estriol are known as endogenous estrogen which have the same steroidal frame with different substituent, leading to difference of physiological activity upon the formation of hydrogen bond with estrogen receptor. In the present study, structures of estrogens and their hydrated clusters in a supersonic jet have been studied by various laser spectroscopic techniques and density functional theory calculation to study how the difference of substituents affects their hydrogen bonding ability. Infrared spectra in the OH stretching region indicate a formation of intramolecular hydrogen-bond in estriol, which may lead to weaker physiological activity among the three estrogens. We also measured electronic and infrared spectra of 1:1 hydrated clusters of estrogen. The results show a switch of stable hydration site from the phenolic OH group to the five member ring by substituting one more OH group.

  15. The role of P450 metabolism in the estrogenic activity of bifenthrin in fish.

    Science.gov (United States)

    DeGroot, Breanna C; Brander, Susanne M

    2014-11-01

    Bifenthrin, a pyrethroid pesticide, is estrogenic in vivo in fishes. However, bifenthrin is documented to be anti-estrogenic in vitro, in the ER-CALUX (estrogen receptor) cell line. We investigated whether metabolite formation is the reason for this incongruity. We exposed Menidia beryllina (inland silversides) to 10ng/l bifenthrin, 10ng/l 4-hydroxy bifenthrin, and 10ng/l bifenthrin with 25μg/l piperonyl butoxide (PBO) - a P450 inhibitor. Metabolite-exposed juveniles had significantly higher estrogen-mediated protein levels (choriogenin) than bifenthrin/PBO-exposed, while bifenthrin alone was intermediate (not significantly different from either). This suggests that metabolites are the main contributors to bifenthrin's in vivo estrogenicity. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. [Bone metabolism and cardiovascular function update. Estrogen and its therapeutic potential for bone and vascular health].

    Science.gov (United States)

    Ohta, Hiroaki

    2014-07-01

    Despite its long-standing role as a "guardian angel" for the female body, estrogen has recently been dethroned from its status as an "elixir" and its use has been restricted due to its oncogenic potential as well as its coagulation system-associated risk. However, it is recognized that estrogen not only works against bone resorption but also improves vascular function. In this regard, it is suggested that estrogen may have a role in improving deteriorated bone quality through its antioxidant action, while this same effect with the SERMs, which may be accounted for by the presence of estrogen, remains yet to be established. Not only evidence needs to be accumulated to support the vascular effects of the SERMs, but their pleiotropic, rather than extra-skeletal, effects, as likely mediated by the estrogen receptors distributed throughout the body, remain to be elucidated.

  17. Characterization of estrogen receptors alpha and beta in uterine leiomyoma cells.

    Science.gov (United States)

    Valladares, Francisco; Frías, Ignacio; Báez, Delia; García, Candelaria; López, Francisco J; Fraser, James D; Rodríguez, Yurena; Reyes, Ricardo; Díaz-Flores, Lucio; Bello, Aixa R

    2006-12-01

    Cellular and subcellular localization of estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) in uterine leiomyomas. Retrospective study. University of La Laguna (ULL) and Canary University Hospital (HUC). Premenopausal and postmenopausal women with uterine leiomyomas. Hysterectomy and myomectomy. Estrogen receptor alpha was only present in smooth muscle cells with variation in the subcellular location in different leiomyomas. Estrogen receptor beta was widely distributed in smooth muscle, endothelial, and connective tissue cells with nuclear location in all cases studied; variations were only found in the muscle cells for this receptor. Estrogens operate in leiomyoma smooth muscle cells through different receptors, alpha and beta. However they only act through the ERbeta in endothelial and connective cells.

  18. Removal of steroid estrogens from wastewater using granular activated carbon: comparison between virgin and reactivated carbon.

    Science.gov (United States)

    Rowsell, Victoria Francesca; Pang, Dawn Sok Cheng; Tsafou, Foteini; Voulvoulis, Nikolaos

    2009-04-01

    This research was set up in response to new European legislation to identify cost-effective treatment for removal of steroid estrogens from effluent. This study aimed to compare estrogen removal of two types of granular activated carbon: virgin (F400) and reactivated (C401) carbon. Rapid, small-scale column tests were conducted with a total bed volume of 24.9 cm3 over three columns, and analysis was carried out using high-performance liquid chromatography. Results demonstrated that C401 performed more efficiently with greater than or equal to 81% estrogen removal in wastewater compared to F400 which produced greater than or equal to 65% estrogen removal. Estrogen removal can be affected by competitive adsorption from natural organic matter present in wastewater. In addition, the physical properties of each carbon had the potential to influence adsorption differently, thus resulting in the observed varied adsorption capability of the two carbons.

  19. Ekspresi Gen CYP19 Aromatase, Estrogen, Androgen pada penderita Periodontitis Agresif

    Directory of Open Access Journals (Sweden)

    Dahlia Herawati

    2016-11-01

    Full Text Available Kepadatan tulang tubuh ditentukan oleh gen CYP19 aromatase, hormon estrogen dan androgen. Pada periodontitis agresif terjadi perkembangan cepat kerusakan tulang alveolar, dan kerusakan tulang alveoler tersebut tidak diimbangioleh regenerasi tulang. Tujuan penelitian ini adalah menunjukkan ekspresi gen CYP19 aromatase, estrogen, androgen pada penderita periodontitis agresif agar dapat untuk menjadi pertimbangan pada saat melakukan perawatan periodontal. Metode penelitian, pemeriksaan ekspresi gen aromatse CYP19 berasal dari spesimen tulang alveolar menggunakan imunohistokimia, pengukuran hormon estrogen dan androgen dari serum menggunakan Vidas: Elfa. Hasil penelitian ekspresi gene CYP19 aromatase pada periodontitis agresif menunjukkan gambaran lebih rendah densitasnya dibandingkan pada nonperiodontitis. Estrogen dan androgen pad aperiodontitis agresif ada kecenderungan lebih rendah dibandingkan pada nonperiodontitis. Kesimpulan regenerasi tulang alveoler pad a periodontitis agresif terhambat karena sedikitnya gen CYP19 aromatase dan hormon estrogen dan androgen yang berperan pada pembentukan tulang alveoler kurang memadai.

  20. PI3K in the ventromedial hypothalamic nucleus mediates estrogenic actions on energy expenditure in female mice

    Science.gov (United States)

    Estrogens act in the ventromedial hypothalamic nucleus (VMH) to regulate body weight homeostasis. However, the molecular mechanisms underlying these estrogenic effects are unknown. We show that activation of estrogen receptor-a (ERa) stimulates neural firing of VMH neurons expressing ERa, and these ...

  1. Estrogens regulate neuroinflammatory genes via estrogen receptors α and β in the frontal cortex of middle-aged female rats

    Directory of Open Access Journals (Sweden)

    Mahó Sándor

    2011-07-01

    Full Text Available Abstract Background Estrogens exert anti-inflammatory and neuroprotective effects in the brain mainly via estrogen receptors α (ERα and β (ERβ. These receptors are members of the nuclear receptor superfamily of ligand-dependent transcription factors. This study was aimed at the elucidation of the effects of ERα and ERβ agonists on the expression of neuroinflammatory genes in the frontal cortex of aging female rats. Methods To identify estrogen-responsive immunity/inflammation genes, we treated middle-aged, ovariectomized rats with 17β-estradiol (E2, ERα agonist 16α-lactone-estradiol (16α-LE2 and ERβ agonist diarylpropionitrile (DPN, or vehicle by Alzet minipump delivery for 29 days. Then we compared the transcriptomes of the frontal cortex of estrogen-deprived versus ER agonist-treated animals using Affymetrix Rat230 2.0 expression arrays and TaqMan-based quantitative real-time PCR. Microarray and PCR data were evaluated by using Bioconductor packages and the RealTime StatMiner software, respectively. Results Microarray analysis revealed the transcriptional regulation of 21 immunity/inflammation genes by 16α-LE2. The subsequent comparative real-time PCR study analyzed the isotype specific effects of ER agonists on neuroinflammatory genes of primarily glial origin. E2 regulated the expression of sixteen genes, including down-regulation of complement C3 and C4b, Ccl2, Tgfb1, macrophage expressed gene Mpeg1, RT1-Aw2, Cx3cr1, Fcgr2b, Cd11b, Tlr4 and Tlr9, and up-regulation of defensin Np4 and RatNP-3b, IgG-2a, Il6 and ER gene Esr1. Similar to E2, both 16α-LE2 and DPN evoked up-regulation of defensins, IgG-2a and Il6, and down-regulation of C3 and its receptor Cd11b, Ccl2, RT1-Aw2 and Fcgr2b. Conclusions These findings provide evidence that E2, 16α-LE2 and DPN modulate the expression of neuroinflammatory genes in the frontal cortex of middle-aged female rats via both ERα and ERβ. We propose that ERβ is a promising target to suppress

  2. Identification of estrogenic activity change in sewage, industrial and livestock effluents by gamma-irradiation

    International Nuclear Information System (INIS)

    Ahn, Byeong-Yong; Kang, Sung-Wook; Yoo, Jisu; Kim, Woong-Ki; Bae, Paek-Hyun; Jung, Jinho

    2012-01-01

    In this study, reduction of estrogenic activity in three different types of effluents from sewage, industrial and livestock wastewater treatment plants by gamma-irradiation was investigated using the yeast two-hybrid assay. After gamma-ray treatment at a dose of 10 kGy, estrogenic activities of sewage, industrial and livestock effluents decreased from 4.4 to 3.0, 1.5 to 1.0 and 16 to 9.9 ng-EEQ L −1 , respectively. The substantial reduction of estrogenic activity in livestock effluent was attributable to the degradation of 17β-estradiol (E2), estrone (E1) and 17α-ethynylestradiol (EE2). Although bisphenol A (BPA) was found at the highest concentration in all effluents, its contribution to the estrogenic activity was not significant due to its low relative estrogenic potency. Meanwhile, the calculated estrogenic activity based on concentrations of E2, E1, EE2 and BPA in the effluents significantly differed from the measured ones. Overestimation may have resulted by dissolved organic matters in effluents inhibiting the estrogenic activity of E2, E1, EE2 and BPA, whereas underestimation was likely due to estrogenic by-products generated by gamma-irradiation. - Highlights: ► Livestock effluent showed strong estrogenic activity due to E2, E1 and EE2. ► EE2 remained in all effluents after gamma-irradiation even at a dose of 10 kGy. ► DOMs in effluents inhibited degradation and activity of estrogenic compounds.

  3. Estrogenic plant foods of red colobus monkeys and mountain gorillas in Uganda.

    Science.gov (United States)

    Wasserman, Michael D; Taylor-Gutt, Alexandra; Rothman, Jessica M; Chapman, Colin A; Milton, Katharine; Leitman, Dale C

    2012-05-01

    Phytoestrogens, or naturally occurring estrogen-mimicking compounds, are found in many human plant foods, such as soybeans (Glycine max) and other legumes. Because the consumption of phytoestrogens may result in both health benefits of protecting against estrogen-dependent cancers and reproductive costs of disrupting the developing endocrine system, considerable biomedical research has been focused on the physiological and behavioral effects of these compounds. Despite this interest, little is known about the occurrence of phytoestrogens in the diets of wild primates, nor their likely evolutionary importance. We investigated the prevalence of estrogenic plant foods in the diets of two folivorous primate species, the red colobus monkey (Procolobus rufomitratus) of Kibale National Park and mountain gorilla (Gorilla beringei) of Bwindi Impenetrable National Park, both in Uganda. To examine plant foods for estrogenic activity, we screened 44 plant items (species and part) comprising 78.4% of the diet of red colobus monkeys and 53 plant items comprising 85.2% of the diet of mountain gorillas using transient transfection assays. At least 10.6% of the red colobus diet and 8.8% of the gorilla diet had estrogenic activity. This was mainly the result of the red colobus eating three estrogenic staple foods and the gorillas eating one estrogenic staple food. All estrogenic plants exhibited estrogen receptor (ER) subtype selectivity, as their phytoestrogens activated ERβ, but not ERα. These results demonstrate that estrogenic plant foods are routinely consumed by two folivorous primate species. Phytoestrogens in the wild plant foods of these two species and many other wild primates may have important implications for understanding primate reproductive ecology. Copyright © 2012 Wiley Periodicals, Inc.

  4. Twenty years of the G protein-coupled estrogen receptor GPER: Historical and personal perspectives.

    Science.gov (United States)

    Barton, Matthias; Filardo, Edward J; Lolait, Stephen J; Thomas, Peter; Maggiolini, Marcello; Prossnitz, Eric R

    2018-02-01

    Estrogens play a critical role in many aspects of physiology, particularly female reproductive function, but also in pathophysiology, and are associated with protection from numerous diseases in premenopausal women. Steroids and the effects of estrogen have been known for ∼90 years, with the first evidence for a receptor for estrogen presented ∼50 years ago. The original ancestral steroid receptor, extending back into evolution more than 500 million years, was likely an estrogen receptor, whereas G protein-coupled receptors (GPCRs) trace their origins back into history more than one billion years. The classical estrogen receptors (ERα and ERβ) are ligand-activated transcription factors that confer estrogen sensitivity upon many genes. It was soon apparent that these, or novel receptors may also be responsible for the "rapid"/"non-genomic" membrane-associated effects of estrogen. The identification of an orphan GPCR (GPR30, published in 1996) opened a new field of research with the description in 2000 that GPR30 expression is required for rapid estrogen signaling. In 2005-2006, the field was greatly stimulated by two studies that described the binding of estrogen to GPR30-expressing cell membranes, followed by the identification of a GPR30-selective agonist (that lacked binding and activity towards ERα and ERβ). Renamed GPER (G protein-coupled estrogen receptor) by IUPHAR in 2007, the total number of articles in PubMed related to this receptor recently surpassed 1000. In this article, the authors present personal perspectives on how they became involved in the discovery and/or advancement of GPER research. These areas include non-genomic effects on vascular tone, receptor cloning, molecular and cellular biology, signal transduction mechanisms and pharmacology of GPER, highlighting the roles of GPER and GPER-selective compounds in diseases such as obesity, diabetes, and cancer and the obligatory role of GPER in propagating cardiovascular aging, arterial

  5. Estrogen receptor-dependent effects of bisphenol a

    Directory of Open Access Journals (Sweden)

    P. Bulzomi

    2011-01-01

    Full Text Available Bisphenol A (BPA, commonly used as building block of polycarbonate plastics, significantly affects human and animal health interfering with the action of natural hormones. Within BPA disrupting effects, a mitogenic activity and, consequently, an increased incidence of neoplastic transformations has been reported in exposed organisms. Among the several mechanisms proposed for the mitogenic BPA effects, its ability to bind to estrogen receptors (ERα and ERβ deserves particular attention. Aim of this work is to investigate ERα- and ERβ-dependent mechanisms underlying BPA proliferative effect. Binding assay confirms that BPA binds to both ERs. Cell vitality assay and Western blot analysis of protein involved in cell proliferation demonstrate that BPA acts as a double side disruptor of estrogenic effects. In fact in the presence of ERα, BPA mimics E2, increasing cell proliferation. On the contrary, in the presence of ERβ, BPA acts as an E2 antagonist preventing the hormone-induced cancer cells apoptosis. These two divergent aspects could act synergistically in the exposed organisms leading to the disruption of the balance between proliferation and apoptosis typical of E2 effects.

  6. Oxytocin and Estrogen Receptor β in the Brain: An Overview.

    Science.gov (United States)

    Acevedo-Rodriguez, Alexandra; Mani, Shaila K; Handa, Robert J

    2015-01-01

    Oxytocin (OT) is a neuropeptide synthesized primarily by neurons of the paraventricular and supraoptic nuclei of the hypothalamus. These neurons have axons that project into the posterior pituitary and release OT into the bloodstream to promote labor and lactation; however, OT neurons also project to other brain areas where it plays a role in numerous brain functions. OT binds to the widely expressed OT receptor (OTR), and, in doing so, it regulates homeostatic processes, social recognition, and fear conditioning. In addition to these functions, OT decreases neuroendocrine stress signaling and anxiety-related and depression-like behaviors. Steroid hormones differentially modulate stress responses and alter OTR expression. In particular, estrogen receptor β activation has been found to both reduce anxiety-related behaviors and increase OT peptide transcription, suggesting a role for OT in this estrogen receptor β-mediated anxiolytic effect. Further research is needed to identify modulators of OT signaling and the pathways utilized and to elucidate molecular mechanisms controlling OT expression to allow better therapeutic manipulations of this system in patient populations.

  7. Steroid production and estrogen binding in flowers of Gladiolus

    International Nuclear Information System (INIS)

    Adler, J.H.; Wolfe, G.R.; Janik, J.R.

    1987-01-01

    The bioconversion of 3 H-cholesterol to steroids was examined in excised tissue from the pistils and bracts of Gladiolus. Ovary-ovule and stigma-style tissues produce a compound with chromatographic properties on reverse phase HPLC similar to 17β-estradiol (E 2 ). The stigma-style fraction also produced a compound that chromatographed similarly to progesterone. Bracts and the oxidation controls produced no radiolabeled compounds which were chromatographically similar to E 2 . An endogenous E 2 binding protein was partially characterized from the ovules. The protein binds E 2 , estriol, and diethylstilbesterol whereas testosterone and progesterone do not bind. The total specific binding capacities in the cytosolic and nuclear fractions are 1.6 and 2.2 femtomoles of estradiol per mg of tissue. The dissociation constant is 1.1 x 10 -9 M -1 for both subcellular fractions. The protein-estradiol complex has a sedimentation coefficient of 4.7 +/- 0.1S. The tissue specific biosynthesis of estrogens and the presence of a steroid binding protein similar to a Type 1 estrogen receptor found in mammals is suggestive of a role for steroids in pistil ontogeny

  8. Testosterone and estrogen in multiple sclerosis: from pathophysiology to therapeutics.

    Science.gov (United States)

    Collongues, Nicolas; Patte-Mensah, Christine; De Seze, Jérôme; Mensah-Nyagan, Ayikoe-Guy; Derfuss, Tobias

    2018-06-01

    Neuroprotection and remyelination are two unmet needs in the treatment of multiple sclerosis (MS). Therapeutic potential has been identified with sexual hormones, supported in women by a decrease in MS activity during the pregnancy, in men by a greater severity of symptoms and a faster progression than in women. Areas covered: The therapeutic effect of testosterone and estrogens is reviewed. Both hormones have demonstrated an anti-inflammatory effect. Testosterone has an effect in protecting neurons in culture against glutamate-induced toxicity and oxidative stress, and stimulates myelin formation and regeneration mediated through the neural androgen receptor. In experimental autoimmune encephalomyelitis model, estrogens significantly decrease inflammation in the central nervous system via ERα, while its action on ERβ leads to myelin and axon reparation. Estriol therapy in two phase 2 trials showed a decrease in clinical disease activity and inflammatory parameters in MRI. However, evidence of a therapeutic effect of testosterone is scarce. Expert commentary: Phase 3 trials with estriol as an add-on supplementation are now mandatory. Testosterone is another candidate to be tested in phase 2 trials. These hormones should be considered as an adjunctive therapy. New validated tools are needed to assess their effect on neuroprotection and remyelination.

  9. [Estrogens and feminine brain maturation during adolescence: emergency contraceptive pill].

    Science.gov (United States)

    López Moratalla, Natalia; Errasti Alcalá, Tania; Santiago, Esteban

    2011-01-01

    In the period between puberty and maturity takes place the process of brain maturation. Hormone levels induce changes in neurons and direct the architecture and structural functionality thus affecting patterns of development of different brain areas. The onset of puberty brings with it the invasion of the female brain by high levels of hormones, cyclic surges of estrogen and progesterone in addition to steroids produced in situ. Control centers of emotions (amygdala), memory and learning (hippocampus) and sexual activity (hypothalamus) are modified according to the cyclical concentrations of both hormones. Sex hormones stimulate multimodal actions, both short and longer terms, because neurons in various brain areas have different types of receptors, membrane, cytoplasmic and nuclear. The composition of emergency contraceptive pill (postcoital pill) with high hormonal content raises the urgency of a thorough knowledge about the possible effect that the lack of control of the menstrual cycle in a time of consolidation of brain maturation, can bring in structuring and development of brain circuitry. Changes in the availability of sex steroids during puberty and adolescence underlie psychiatric disorders whose prevalence is typically feminine, such as depression, anxiety disorders. It is a fundamental ethical duty to present scientific data about the influence of estrogen in young female brain maturation, both for full information to potential users, and also to induce the appropriate public health measures.

  10. Inter-laboratory exercise on steroid estrogens in aqueous samples

    Energy Technology Data Exchange (ETDEWEB)

    Heath, E., E-mail: ester.heath@ijs.s [Department of Environmental Sciences, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia); Kosjek, T. [Department of Environmental Sciences, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia); Andersen, H.R.; Holten Luetzhoft, H.-C. [Department of Environmental Engineering, Technical University of Denmark, Miljoevej 113, DK-2800 Kgs. Lyngby (Denmark); Adolfson Erici, M. [Stockholm University, ITM SE-106 91 Stockholm (Sweden); Coquery, M. [Cemagref, U.R. QELY, F-69336 Lyon (France); Duering, R.-A. [Giessen University, Institute of Soil Science and Soil Conservation, Giessen (Germany); Gans, O. [Umweltbundesamt GmbH, Unit Organic Analysis, Spittelauer Laende 5, 1090 Vienna (Austria); Guignard, C. [CRP Gabriel Lippmann, EVA, 41 rue du Brill, L-4422 Belvaux (Luxembourg); Karlsson, P. [Lantmannen Analycen AB, Research and Development, Sjoehagsgatan 3 Box 905, 5319, Lidkoeping (Sweden); Manciot, F. [CAE VEOLIA ENVIRONMENT, 1 Place de Turenne, 94417 Saint Maurice Cedex (France); Moldovan, Z. [National Institute of Research and Development for Isotopic and Molecular Technology, Mass Spectrometry Department, Str. Donath 65-103, 400293 Cluj-Napoca (Romania); Patureau, D. [INRA, UR50, Laboratoire de Biotechnologie de l' Environnemet (LBE), Avenue des etangs, F-11100 Narbonne (France); Cruceru, L. [Pollution Control Department, National Research Institute for Industrial Ecology (ECOIND), Sos.Panduri 90-92, sector 5, Bucharest (Romania); Sacher, F. [DVGW-Technologiezentrum Wasser, Karlsruher Strasse 84, 76139 Karlsruhe (Germany); Ledin, A. [Department of Environmental Engineering, Technical University of Denmark, Miljoevej 113, DK-2800 Kgs. Lyngby (Denmark)

    2010-03-15

    An inter-laboratory comparison exercise was organized among European laboratories, under the aegis of EU COST Action 636: 'Xenobiotics in Urban Water Cycle'. The objective was to evaluate the performance of testing laboratories determining 'Endocrine Disrupting Compounds' (EDC) in various aqueous matrices. As the main task three steroid estrogens: 17alpha-ethinylestradiol, 17beta-estradiol and estrone were determined in four spiked aqueous matrices: tap water, river water and wastewater treatment plant influent and effluent using GC-MS and LC-MS/MS. Results were compared and discussed according to the analytical techniques applied, the accuracy and reproducibility of the analytical methods and the nature of the sample matrices. Overall, the results obtained in this inter-laboratory exercise reveal a high level of competence among the participating laboratories for the detection of steroid estrogens in water samples indicating that GC-MS as well as LC-MS/MS can equally be employed for the analysis of natural and synthetic hormones. - Herein are presented the results of the first international inter-laboratory study on determination of selected steroid hormones in environmental aqueous samples.

  11. Estrogen's Place in the Family of Synaptic Modulators.

    Science.gov (United States)

    Kramár, Enikö A; Chen, Lulu Y; Rex, Christopher S; Gall, Christine M; Lynch, Gary

    2009-01-01

    Estrogen, in addition to its genomic effects, triggers rapid synaptic changes in hippocampus and cortex. Here we summarize evidence that the acute actions of the steroid arise from actin signaling cascades centrally involved in long-term potentiation (LTP). A 10-min infusion of E2 reversibly increased fast EPSPs and promoted theta burst-induced LTP within adult hippocampal slices. The latter effect reflected a lowered threshold and an elevated ceiling for the potentiation effect. E2's actions on transmission and plasticity were completely blocked by latrunculin, a toxin that prevents actin polymerization. E2 also caused a reversible increase in spine concentrations of filamentous (F-) actin and markedly enhanced polymerization caused by theta burst stimulation (TBS). Estrogen activated the small GTPase RhoA, but not the related GTPase Rac, and phosphorylated (inactivated) synaptic cofilin, an actin severing protein targeted by RhoA. An inhibitor of RhoA kinase (ROCK) thoroughly suppressed the synaptic effects of E2. Collectively, these results indicate that E2 engages a RhoA >ROCK> cofilin> actin pathway also used by brain-derived neurotrophic factor and adenosine, and therefore belongs to a family of 'synaptic modulators' that regulate plasticity. Finally, we describe evidence that the acute signaling cascade is critical to the depression of LTP produced by ovariectomy.

  12. Inter-laboratory exercise on steroid estrogens in aqueous samples

    International Nuclear Information System (INIS)

    Heath, E.; Kosjek, T.; Andersen, H.R.; Holten Luetzhoft, H.-C.; Adolfson Erici, M.; Coquery, M.; Duering, R.-A.; Gans, O.; Guignard, C.; Karlsson, P.; Manciot, F.; Moldovan, Z.; Patureau, D.; Cruceru, L.; Sacher, F.; Ledin, A.

    2010-01-01

    An inter-laboratory comparison exercise was organized among European laboratories, under the aegis of EU COST Action 636: 'Xenobiotics in Urban Water Cycle'. The objective was to evaluate the performance of testing laboratories determining 'Endocrine Disrupting Compounds' (EDC) in various aqueous matrices. As the main task three steroid estrogens: 17α-ethinylestradiol, 17β-estradiol and estrone were determined in four spiked aqueous matrices: tap water, river water and wastewater treatment plant influent and effluent using GC-MS and LC-MS/MS. Results were compared and discussed according to the analytical techniques applied, the accuracy and reproducibility of the analytical methods and the nature of the sample matrices. Overall, the results obtained in this inter-laboratory exercise reveal a high level of competence among the participating laboratories for the detection of steroid estrogens in water samples indicating that GC-MS as well as LC-MS/MS can equally be employed for the analysis of natural and synthetic hormones. - Herein are presented the results of the first international inter-laboratory study on determination of selected steroid hormones in environmental aqueous samples.

  13. Chronic hepatitis C and fibrosis: evidences for possible estrogen benefits

    Directory of Open Access Journals (Sweden)

    Liana Codes

    Full Text Available The main injury caused by hepatitis C virus is the hepatic fibrosis, as a result of a chronic inflammatory process in the liver characterized by the deposit of components from the extracellular matrix. The fibrosis development leads to the modification of the hepatic architecture, of the hepatocellular function and to irregularities in the microcirculation. The tissue remodeling process observed in fibrosis has stellate cells, located at the space of Disse, as main acting agents. These cells, in response to a harmful stimulus, undergo phenotypic changes from non-proliferating cells to proliferating cells that express a- smooth-muscle actin (a-SMA, a process called as transdifferentiation. There are evidences that the oxidative stress is involved in the chronic liver disease and serves as bond between the injury and the hepatic fibrosis. A number of studies suggest that the estrogen, at physiological levels, presents an antifibrogenic action probably through an antioxidant effect, decreasing the levels of lipid peroxidation products in the liver and blood, thus inhibiting the myofibroblastic transformation of stellate cells and contributing for gender-associated differences in relation to the fibrosis development. The aim of this paper was to describe data from literature concerning the interaction between chronic hepatitis C and estrogens, pregnancy, use of oral contraceptives, menopause and hormone reposition therapy.

  14. Expression of Estrogen Receptor Alpha in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Parvin Rajabi

    2017-01-01

    Full Text Available Background: Features of malignant melanoma (MM vary in the different geographic regions of the world. This may be attributable to environmental, ethnic, and genetic factors. The aim of this study was to determine the expression of estrogen receptor alpha (ER-α in MM in Isfahan, Iran. Materials and Methods: This study was planned as a descriptive, analytical, cross-sectional investigation. During this study, paraffin-embedded tissue blocks of patients with a histopathologic diagnosis of MM was studied for ER-α using immunohistochemistry (IHC. Results: In this study, 38 patients (female/male; 20/18 with a definite diagnosis of malignant cutaneous melanoma and mean age of 52.4 ± 11.2 years were investigated. Using envision IHC staining, there were not any cases with ER-α expression. Conclusion: In confirmation to the most previous studies, expression of ER-α was negative in MM. It is recommended to investigate the expression of estrogen receptor beta and other markers in MM.

  15. Estrogen receptors in human thyroid gland. An immunohistochemical study

    International Nuclear Information System (INIS)

    Arain, Shaukat A.; Shah, Munawar H.; Jamal, Qamar; Meo, Sultan A.

    2003-01-01

    The objective of this study is to determine the estrogen receptors (ER) status (present in the nucleous of cell) in the thyroid gland tissues. For this purpose 50 previously diagnosed cases of various thyroid lesions were selected from the Surgical Pathology Records of Pathology Department, Basic Medical Sciences Institute,Jinnah Postgraduate. Medical Center,Karachi,Pakistan between March and August 2000.The staining was performed on formalin fixed paraffin embeded tissues using monoclonal anti-ER anti-body (clone1D5).Out of 50 cases,8 were noduler goiter,9 cases of adenoma 19 papillary carcinoma, 10 follicular and 4 cases were of medullary carcinoma. Surrounding normal tissue was available in 25 (50%) cases, 4 non-neoplastic and 21 neoplastic lesions.Out of 50 cases ,10(20%) and 40(80%) were females, the youngest patient was a 15-year-old female and the eldest patient was a 56-years-old male. Despite the availability of normal thyroid tissue and a wide range of lesions, none of our cases showed the positive staining. In contrary to many earlier reports by immunohistochemical method using monoclonal antibody (clone1D5) on formalin- fixed praffin-embedded thyroid tissues, the ER is not detectable. The effect of Estrogen on thyroid gland may be indirect one. (author)

  16. The distribution of estrogen receptor in various organs of rabbit

    International Nuclear Information System (INIS)

    Son, H.Y.; In, J.W.; Min, B.S.

    1978-01-01

    For clinical application of radioreceptor assay, we studied preliminarily the distribution of estrogen receptor in various organs of rabbit by a dextran-charcoal method using 6,7- 3 H-es-tradiol. The results were expressed as binding index, which is the ratio of specific estradiol receptor binding radioactivity to total radioactivity. The materials consist of 5 female rabbits and 3 male rabbits. For female rabbits the binding index was highest in the uterine tissue. This binding index of the uterine tissue was 9.4 times that of the liver, 21.9 times that of the kidney, 24.6 times that of the brain, 28.1 times that of the lung and 65.7 times that of the muscle. For male rabbits the binding index was highest in the liver and decreased in the order of the kidney, the testis, the lung, the brain and the muscle. It is suggested that the estrogen receptor is not confined to any specific target organ but is widely distributed in the various organs, to a different degree. (author)

  17. The Distribution of Estrogen Receptor in Various Organs of Rabbit

    International Nuclear Information System (INIS)

    Son, Ho Young; In, Jae Whan; Min, Byong Sok

    1978-01-01

    For clinical application of radioreceptor assay, we studied preliminarily the distribution of estrogen receptor in various organs of rabbit by a dextran-charcoal method using 6, 7- 3 H-estradiol. The results were expressed as binding index, which is the ratio of specific estradiol receptor binding radioactivity to total radioactivity. The materials consist of 5 female rabbits and 3 male rabbits. The results were as follows: 1) Female rabbits. The binding index was highest in the uterine tissue. This binding index of the uterine tissue was 9.4 times that of the liver, 21.9 times that of the kidney, 24.6 times that of the brain, 28.1 times that of the lung and 65.7 times that of the muscle. 2) Male rabbits. The binding index was highest in the liver and decreased in the order of the kidney, the testis, the lung, the brain and the muscle. It is suggested that the estrogen receptor is not confined to any specific target organ but is widely distributed in the various organs, to a different degree.

  18. Oxytocin and Estrogen Receptor β in the Brain: An Overview

    Directory of Open Access Journals (Sweden)

    Alexandra eAcevedo-Rodriguez

    2015-10-01

    Full Text Available Oxytocin is a neuropeptide synthesized primarily by neurons of the paraventricular and supraoptic nuclei of the hypothalamus. These neurons have axons that project into the posterior pituitary and release oxytocin into the bloodstream to promote labor and lactation; however, oxytocin neurons also project to other brain areas where it plays a role in numerous brain functions. Oxytocin binds to the widely expressed oxytocin receptor, and, in doing so, it regulates homeostatic processes, social recognition and fear conditioning. In addition to these functions, oxytocin decreases neuroendocrine stress signaling and anxiety-related and depression-like behaviors. Steroid hormones differentially modulate stress responses and alter oxytocin receptor expression. In particular, estrogen receptor β activation has been found to both reduce anxiety-related behaviors and increase oxytocin peptide transcription, suggesting a role for oxytocin in this estrogen receptor β mediated anxiolytic effect. Further research is needed to identify modulators of oxytocin signaling and the pathways utilized and to elucidate molecular mechanisms controlling oxytocin expression to allow better therapeutic manipulations of this system in patient populations.

  19. Evaluation of Estrogenic Activity of Licorice Species in Comparison with Hops Used in Botanicals for Menopausal Symptoms

    Science.gov (United States)

    Hajirahimkhan, Atieh; Simmler, Charlotte; Yuan, Yang; Anderson, Jeffrey R.; Chen, Shao-Nong; Nikolić, Dejan; Dietz, Birgit M.; Pauli, Guido F.; van Breemen, Richard B.; Bolton, Judy L.

    2013-01-01

    The increased cancer risk associated with hormone therapies has encouraged many women to seek non-hormonal alternatives including botanical supplements such as hops (Humulus lupulus) and licorice (Glycyrrhiza spec.) to manage menopausal symptoms. Previous studies have shown estrogenic properties for hops, likely due to the presence of 8-prenylnarigenin, and chemopreventive effects mainly attributed to xanthohumol. Similarly, a combination of estrogenic and chemopreventive properties has been reported for various Glycyrrhiza species. The major goal of the current study was to evaluate the potential estrogenic effects of three licorice species (Glycyrrhiza glabra, G. uralensis, and G. inflata) in comparison with hops. Extracts of Glycyrrhiza species and spent hops induced estrogen responsive alkaline phosphatase activity in endometrial cancer cells, estrogen responsive element (ERE)-luciferase in MCF-7 cells, and Tff1 mRNA in T47D cells. The estrogenic activity decreased in the order H. lupulus > G. uralensis > G. inflata > G. glabra. Liquiritigenin was found to be the principle phytoestrogen of the licorice extracts; however, it exhibited lower estrogenic effects compared to 8-prenylnaringenin in functional assays. Isoliquiritigenin, the precursor chalcone of liquiritigenin, demonstrated significant estrogenic activities while xanthohumol, a metabolic precursor of 8-prenylnaringenin, was not estrogenic. Liquiritigenin showed ERβ selectivity in competitive binding assay and isoliquiritigenin was equipotent for ER subtypes. The estrogenic activity of isoliquiritigenin could be the result of its cyclization to liquiritigenin under physiological conditions. 8-Prenylnaringenin had nanomolar estrogenic potency without ER selectivity while xanthohumol did not bind ERs. These data demonstrated that Glycyrrhiza species with different contents of liquiritigenin have various levels of estrogenic activities, suggesting the importance of precise labeling of botanical

  20. Evaluation of estrogenic activity of licorice species in comparison with hops used in botanicals for menopausal symptoms.

    Directory of Open Access Journals (Sweden)

    Atieh Hajirahimkhan

    Full Text Available The increased cancer risk associated with hormone therapies has encouraged many women to seek non-hormonal alternatives including botanical supplements such as hops (Humulus lupulus and licorice (Glycyrrhiza spec. to manage menopausal symptoms. Previous studies have shown estrogenic properties for hops, likely due to the presence of 8-prenylnarigenin, and chemopreventive effects mainly attributed to xanthohumol. Similarly, a combination of estrogenic and chemopreventive properties has been reported for various Glycyrrhiza species. The major goal of the current study was to evaluate the potential estrogenic effects of three licorice species (Glycyrrhiza glabra, G. uralensis, and G. inflata in comparison with hops. Extracts of Glycyrrhiza species and spent hops induced estrogen responsive alkaline phosphatase activity in endometrial cancer cells, estrogen responsive element (ERE-luciferase in MCF-7 cells, and Tff1 mRNA in T47D cells. The estrogenic activity decreased in the order H. lupulus > G. uralensis > G. inflata > G. glabra. Liquiritigenin was found to be the principle phytoestrogen of the licorice extracts; however, it exhibited lower estrogenic effects compared to 8-prenylnaringenin in functional assays. Isoliquiritigenin, the precursor chalcone of liquiritigenin, demonstrated significant estrogenic activities while xanthohumol, a metabolic precursor of 8-prenylnaringenin, was not estrogenic. Liquiritigenin showed ERβ selectivity in competitive binding assay and isoliquiritigenin was equipotent for ER subtypes. The estrogenic activity of isoliquiritigenin could be the result of its cyclization to liquiritigenin under physiological conditions. 8-Prenylnaringenin had nanomolar estrogenic potency without ER selectivity while xanthohumol did not bind ERs. These data demonstrated that Glycyrrhiza species with different contents of liquiritigenin have various levels of estrogenic activities, suggesting the importance of precise labeling of

  1. Auger electron emission initiated by the creation of valence-band holes in graphene by positron annihilation.

    Science.gov (United States)

    Chirayath, V A; Callewaert, V; Fairchild, A J; Chrysler, M D; Gladen, R W; Mcdonald, A D; Imam, S K; Shastry, K; Koymen, A R; Saniz, R; Barbiellini, B; Rajeshwar, K; Partoens, B; Weiss, A H

    2017-07-13

    Auger processes involving the filling of holes in the valence band are thought to make important contributions to the low-energy photoelectron and secondary electron spectrum from many solids. However, measurements of the energy spectrum and the efficiency with which electrons are emitted in this process remain elusive due to a large unrelated background resulting from primary beam-induced secondary electrons. Here, we report the direct measurement of the energy spectra of electrons emitted from single layer graphene as a result of the decay of deep holes in the valence band. These measurements were made possible by eliminating competing backgrounds by employing low-energy positrons (holes by annihilation. Our experimental results, supported by theoretical calculations, indicate that between 80 and 100% of the deep valence-band holes in graphene are filled via an Auger transition.

  2. Multistage-targeted pH-responsive polymer conjugate of Auger electron emitter: optimized design and in vivo activity

    Czech Academy of Sciences Publication Activity Database

    Sedláček, Ondřej; Kučka, Jan; Mattová, J.; Pařízek, Martin; Studenovský, Martin; Zadinová, M.; Pouckova, P.; Hrubý, Martin

    2014-01-01

    Roč. 63, 15 October (2014), s. 216-225 ISSN 0928-0987 R&D Projects: GA MPO FR-TI4/625; GA MŠk(CZ) LH14079 Grant - others:AV ČR(CZ) M200501201 Program:M Institutional support: RVO:61389013 ; RVO:67985823 Keywords : ellipticine * drug delivery * radiotherapy Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.350, year: 2014

  3. Auger electron spectroscopy of the surface of a pipe-like solid C60+18n

    International Nuclear Information System (INIS)

    Khvostov, V.V.; Chernozatonskij, L.A.; Kosakovskaya, Z.Ya.; Babaev, V.V.; Guseva, M.B.

    1992-01-01

    Auger and electron energy loss spectra obtained when probing the surface of nanofiber carbon material by an electron beam point out to C 60 football-type of covers with the outlet to the surface of nanopipe carbon molecules

  4. Characterization of oxide layers on amorphous Mg-based alloys by Auger electron spectroscopy with sputter depth profiling

    Energy Technology Data Exchange (ETDEWEB)

    Baunack, S.; Wolff, U. [Leibniz-Institut fuer Festkoerper- und Werkstoffforschung Dresden, Postfach 270016, 01171, Dresden (Germany); Subba Rao, R.V. [Indira Ghandi Centre for Atomic Research, 603 102, Kalpakkam, Tamil Nadu (India)

    2003-04-01

    Amorphous ribbons of Mg-Y-TM-[Ag](TM: Cu, Ni), prepared by melt spinning, were subjected to electrochemical investigations. Oxide layers formed anodically under potentiostatic control in different electrolytes were investigated by AES and sputter depth profiling. Problems and specific features of characterization of the composition of oxide layers and amorphous ternary or quaternary Mg-based alloys have been investigated. In the alloys the Mg(KL{sub 23}L{sub 23}) peak exhibits a different shape compared to that in the pure element. Analysis of the peak of elastically scattered electrons proved the absence of plasmon loss features, characteristic of pure Mg, in the alloy. A different loss feature emerges in Mg(KL{sub 23}L{sub 23}) and Cu(L{sub 23}VV). The system Mg-Y-TM-[Ag] suffers preferential sputtering. Depletion of Mg and enrichment of TM and Y are found. This is attributed mainly to the preferential sputtering of Mg. Thickness and composition of the formed oxide layer depend on the electrochemical treatment. After removing the oxide by sputtering the concentration of the underlying alloy was found to be affected by the treatment. (orig.)

  5. Identification of very low energy projectile autoionizing transitions in high velocity collisions using zero-degree Auger electron spectroscopy

    International Nuclear Information System (INIS)

    Zouros, T.J.M.; Liao, C.; Montenegro, E.C.; Hagmann, S.; Richard, P.; Grabbe, S.; Bhalla, C.P.; Wong, K.L.

    1995-01-01

    The unusual looking ''mesa''-shaped cusp observed in O 3+ collisions with He [N. Stolterfoht et al., Proc. 2nd US-Mexico Symp. on Atomic and Molecular Phy. eds. A. Cisneros and T. Morgan (Instituto de Fysica, Cuernavaca, Mexico, 1986) p. 51.], has been investigated using zero-degree electron spectroscopy, in both high resolution singles measurements and lower resolution electron-projectile coincidence measurements at 10, 15 and 23 MeV. The high resolution studies indicate the ''mesa'' peak to be actually composed of primarily two (other than the cusp) very strong autoionizing peaks corresponding to energies of 60 and 100 meV in the emitter frame. The coincidence studies, indicate these lines to originate from excitation of the O 3+ ion followed by autoionization. Ongoing Hartree-Fock-Slater calculations, severely tested at these extremely small transition energies, indicate that these lines can indeed result from the autoionization of t he O 3+ (1s 2 2s2p5l) Rydberg states produced during the collision. Furthermore, the unusually sharp edges of these lines giving rise to the characteristic ''mesa''-shape look, can be explained in terms of the kinematic constraints imposed by the energy and angular acceptance range of the spectrometer. (orig.)

  6. Simulation of Auger electron emission from nanometer-size gold targets using the Geant4 Monte Carlo simulation toolkit

    Energy Technology Data Exchange (ETDEWEB)

    Incerti, S., E-mail: sebastien.incerti@tdt.edu.vn [Division of Nuclear Physics, Ton Duc Thang University, Tan Phong Ward, District 7, Ho Chi Minh City (Viet Nam); Faculty of Applied Sciences, Ton Duc Thang University, Tan Phong Ward, District 7, Ho Chi Minh City (Viet Nam); Univ. Bordeaux, CENBG, UMR 5797, F-33170 Gradignan (France); CNRS, IN2P3, CENBG, UMR 5797, F-33170 Gradignan (France); Suerfu, B.; Xu, J. [Department of Physics, Princeton University, Princeton, NJ (United States); Ivantchenko, V. [Ecoanalytica, Moscow (Russian Federation); Geant4 Associates International Ltd, Hebden Bridge (United Kingdom); Mantero, A. [SWHARD srl, via Greto di Cornigliano 6r, 16152 Genova (Italy); Brown, J.M.C. [School of Mathematics and Physics, Queen’s University Belfast, Belfast, Northern Ireland (United Kingdom); Bernal, M.A. [Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, SP (Brazil); Francis, Z. [Université Saint Joseph, Faculty of Sciences, Department of Physics, Beirut (Lebanon); Karamitros, M. [Notre Dame Radiation Laboratory, University of Notre Dame, Notre Dame, IN (United States); Tran, H.N. [Division of Nuclear Physics, Ton Duc Thang University, Tan Phong Ward, District 7, Ho Chi Minh City (Viet Nam); Faculty of Applied Sciences, Ton Duc Thang University, Tan Phong Ward, District 7, Ho Chi Minh City (Viet Nam)

    2016-04-01

    A revised atomic deexcitation framework for the Geant4 general purpose Monte Carlo toolkit capable of simulating full Auger deexcitation cascades was implemented in June 2015 release (version 10.2 Beta). An overview of this refined framework and testing of its capabilities is presented for the irradiation of gold nanoparticles (NP) with keV photon and MeV proton beams. The resultant energy spectra of secondary particles created within and that escape the NP are analyzed and discussed. It is anticipated that this new functionality will improve and increase the use of Geant4 in the medical physics, radiobiology, nanomedicine research and other low energy physics fields.

  7. Electron Beam Damage in Poly(Vinyl Chloride) and Poly(Acrylonitrile) as Observed by Auger Electron Spectroscopy

    International Nuclear Information System (INIS)

    Lea, Alan S.; Engelhard, Mark H.; Baer, Donald R.

    2003-01-01

    AES spectra of spun-cast films of poly(vinyl chloride) (PVC) and poly(acrylonitrile) (PAN) were collected over a period of time to determine specimen damage during exposure to a 10kV electron beam. For the PVC, loss of chlorine was observed over a period of 203 minutes to the extent that the final chlorine concentration was only 20% of its original value. PAN exhibited a loss in nitrogen content over a period of 120 minutes, but the rate of damage to the polymer was significantly less than PVC. Figure 1 shows the atomic concentration in the PVC film as a function of dose (time). It takes a dose of approximately 7.0x10-5 Ccm-5 for the chlorine concentration to fall from its original value by 10% (one definition of critical dose). Figure 2 shows a similar drop in nitrogen concentration in the PAN film as a function of dose. For this polymer, it takes a dose of 1.3x10-3 Ccm-2 for the nitrogen concentration to fall by 10%

  8. The estrogen-injected female mouse: new insight into the etiology of PCOS

    Directory of Open Access Journals (Sweden)

    Freeh Steven M

    2009-05-01

    Full Text Available Abstract Background Female mice and rats injected with estrogen perinatally become anovulatory and develop follicular cysts. The current consensus is that this adverse response to estrogen involves the hypothalamus and occurs because of an estrogen-induced alteration in the GnRH delivery system. Whether or not this is true has yet to be firmly established. The present study examined an alternate possibility in which anovulation and cyst development occurs through an estrogen-induced disruption in the immune system, achieved through the intermediation of the thymus gland. Methods, Results and Conclusion A putative role for the thymus in estrogen-induced anovulation and follicular cyst formation (a model of PCOS was examined in female mice by removing the gland prior to estrogen injection. Whereas all intact, female mice injected with 20 ug estrogen at 5–7 days of age had ovaries with follicular cysts, no cysts were observed in animals in which thymectomy at 3 days of age preceded estrogen injection. In fact, after restoring immune function by thymocyte replacement, the majority of thymectomized, estrogen-injected mice had ovaries with corpora lutea. Thus, when estrogen is unable to act on the thymus, ovulation occurs and follicular cysts do not develop. This implicates the thymus in the cysts' genesis and discounts the role of the hypothalamus. Subsequent research established that the disease is transferable by lymphocyte infusion. Transfer took place between 100-day-old estrogen-injected and 15-day-old naïve mice only when recipients were thymectomized at 3 days of age. Thus, a prerequisite for cyst formation is the absence of regulatory T cells. Their absence in donor mice was judged to be the result of an estrogen-induced increase in the thymus' vascular permeability, causing de facto circumvention of the final stages of regulatory T cell development. The human thymus has a similar vulnerability to steroid action during the fetal stage. We

  9. Assessment of cellular estrogenic activity based on estrogen receptor-mediated reduction of soluble-form catechol-O-methyltransferase (COMT expression in an ELISA-based system.

    Directory of Open Access Journals (Sweden)

    Philip Wing-Lok Ho

    Full Text Available Xenoestrogens are either natural or synthetic compounds that mimic the effects of endogenous estrogen. These compounds, such as bisphenol-A (BPA, and phthalates, are commonly found in plastic wares. Exposure to these compounds poses major risk to human health because of the potential to cause endocrine disruption. There is huge demand for a wide range of chemicals to be assessed for such potential for the sake of public health. Classical in vivo assays for endocrine disruption are comprehensive but time-consuming and require sacrifice of experimental animals. Simple preliminary in vitro screening assays can reduce the time and expense involved. We previously demonstrated that catechol-O-methyltransferase (COMT is transcriptionally regulated by estrogen via estrogen receptor (ER. Therefore, detecting corresponding changes of COMT expression in estrogen-responsive cells may be a useful method to estimate estrogenic effects of various compounds. We developed a novel cell-based ELISA to evaluate cellular response to estrogenicity by reduction of soluble-COMT expression in ER-positive MCF-7 cells exposed to estrogenic compounds. In contrast to various existing methods that only detect bioactivity, this method elucidates direct physiological effect in a living cell in response to a compound. We validated our assay using three well-characterized estrogenic plasticizers - BPA, benzyl butyl phthalate (BBP, and di-n-butyl phthalate (DBP. Cells were exposed to either these plasticizers or 17β-estradiol (E2 in estrogen-depleted medium with or without an ER-antagonist, ICI 182,780, and COMT expression assayed. Exposure to each of these plasticizers (10(-9-10(-7M dose-dependently reduced COMT expression (p<0.05, which was blocked by ICI 182,780. Reduction of COMT expression was readily detectable in cells exposed to picomolar level of E2, comparable to other in vitro assays of similar sensitivity. To satisfy the demand for in vitro assays targeting different

  10. In vivo imaging of brain estrogen receptors in rats : a 16α-18F-fluoro-17β-estradiol PET study

    NARCIS (Netherlands)

    Khayum, Mohammed A; de Vries, Erik F J; Glaudemans, Andor W J M; Dierckx, Rudi A J O; Doorduin, Janine

    UNLABELLED: The steroid hormone estrogen is important for brain functioning and is thought to be involved in brain diseases, such as Alzheimer disease and depression. The action of estrogen is mediated by estrogen receptors (ERs). To understand the role of estrogens in brain functioning, it is

  11. High-throughput screening and mechanism-based evaluation of estrogenic botanical extracts

    Science.gov (United States)

    Overk, Cassia R.; Yao, Ping; Chen, Shaonong; Deng, Shixing; Imai, Ayano; Main, Matthew; Schinkovitz, Andreas; Farnsworth, Norman R.; Pauli, Guido F.; Bolton, Judy L.

    2009-01-01

    Symptoms associated with menopause can greatly affect the quality of life for women. Botanical dietary supplements have been viewed by the public as safe and effective despite a lack of evidence indicating a urgent necessity to standardize these supplements chemically and biologically. Seventeen plants were evaluated for estrogenic biological activity using standard assays: competitive estrogen receptor (ER) binding assay for both alpha and beta subtypes, transient transfection of the estrogen response element luciferase plasmid into MCF-7 cells expressing either ER alpha or ER beta, and the Ishikawa alkaline phosphatase induction assay for both estrogenic and antiestrogenic activities. Based on the combination of data pooled from these assays, the following was determined: a) a high rate of false positive activity for the competitive binding assays, b) some extracts had estrogenic activity despite a lack of ability to bind the ER, c) one extract exhibited selective estrogen receptor modulator (SERM) activity, and d) several extracts show additive/synergistic activity. Taken together, these data indicate a need to reprioritize the order in which the bioassays are performed for maximal efficiency of programs involving bioassay-guided fractionation. In addition, possible explanations for the conflicts in the literature over the estrogenicity of Cimicifuga racemosa (black cohosh) are suggested. PMID:18473738

  12. Role of estrogens in anterior pituitary gland remodeling during the estrous cycle.

    Science.gov (United States)

    Zárate, S; Zaldivar, V; Jaita, G; Magri, L; Radl, D; Pisera, D; Seilicovich, A

    2010-01-01

    In this review, we analyze the action of estrogens leading to the remodeling of the anterior pituitary gland, especially during the estrous cycle. Proliferation and death of anterior pituitary cells and especially lactotropes is regulated by estrogens, which act by sensitizing these cells to both mitotic and apoptotic stimuli such as TNF-alpha, FasL and dopamine. During the estrous cycle, the changing pattern of gonadal steroids is thought to modulate both cell proliferation and death in the anterior pituitary gland, estrogens being key players in cell turnover. The mechanisms involved in estrogen-modulated cell renewal in the anterior pituitary gland during the estrous cycle could include an increase in the expression of proapoptotic cytokines as well as the increase in the Bax/Bcl-2 ratio at proestrus, when estrogen levels are highest and a peak of apoptosis, in particular of lactotropes, is evident in this gland. Estrogens exert rapid antimitogenic and proapoptotic actions in the anterior pituitary through membrane-associated estrogen receptors, a mechanism that might also be involved in remodeling of this gland during the estrous cycle. Copyright (c) 2010 S. Karger AG, Basel.

  13. Occurrence of estrogenic effects in sewage and industrial wastewaters in Beijing, China

    International Nuclear Information System (INIS)

    Ma Mei; Rao Kaifeng; Wang Zijian

    2007-01-01

    Estrogenic potencies of the effluents or water samples from wastewater treatment plants (WWTPs), industries and hospitals and some receiving rivers in Beijing city were estimated by using a human estrogen receptor recombinant yeast assay. Estrogenic activity of industrial wastewaters was found to range from 0.1 to 13.3 ng EEQ/L and decreased to the range of 0.03-1.6 ng EEQ/L after treatment. Estrogenic activity in WWTP influent ranged from 0.3 to 1.7 ng EEQ/L and decreased to the range of 0.05-0.5 ng EEQ/L after treatment. In the receiving river waters, the estrogenic effect range was 0.1-4.7 ng EEQ/L. These data suggest that treated industrial effluents and WWTP effluents of concern are not the only source of estrogenic pollution in surface waters in Beijing city. EEQ levels in Beijing river water are likely attributable to untreated municipal and industrial wastewaters discharged directly into the river. - Estrogenic activity in Beijing river water is attributed to direct discharges of untreated municipal and industrial wastewaters

  14. Disturbance of Mammary UDP-Glucuronosyltransferase Represses Estrogen Metabolism and Exacerbates Experimental Breast Cancer.

    Science.gov (United States)

    Zhou, Xueyan; Zheng, Ziqiang; Xu, Chang; Wang, Juan; Min, Mengjun; Zhao, Yun; Wang, Xi; Gong, Yinhan; Yin, Jiale; Guo, Meng; Guo, Dong; Zheng, Junnian; Zhang, Bei; Yin, Xiaoxing

    2017-08-01

    The progression of breast cancer is closely related to the levels of estrogens within the body. UDP-glucuronosyltransferase (UGT) is an important class of phase II metabolizing enzymes, playing a pivotal role in detoxifying steroid hormone. In the present study, we aim at uncovering the potential dysregulation pattern of UGT and its role in estrogen metabolism and in the pathogenesis of breast cancer. Female Sprague-Dawley rats were treated with 100 mg/kg dimethylbenz(a)anthracene (DMBA) to induce breast cancer. Our results showed that the expression and activity of UGT in mammary tissues were downregulated significantly in DMBA rats. Consistent with this, levels of estradiol, 4-hydroxylated estradiol, and 2-hydroxylated estradiol were increased in both mammary tissues and serum, supporting a notable accumulation of toxic estrogen species in the target tissue of breast cancer. In addition, we also observed the decreased cell migration, cell proliferation, and DNA damage in UGT-transfected MCF-7 cells, suggesting a protective role of UGT against estrogen-induced mammary carcinogenesis. Taken together, these results indicated that accumulation of estrogens induced by UGT deficiency is a critical factor to induce the development of breast cancer. UGT contributes to estrogen elimination, and its glucuronidation capacity influences the estrogen signaling pathway and the pathogenesis of breast cancer. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. Estrogens of multiple classes and their role in mental health disease mechanisms

    Directory of Open Access Journals (Sweden)

    Cheryl S Watson

    2010-06-01

    Full Text Available Cheryl S Watson1, Rebecca A Alyea1, Kathryn A Cunningham2, Yow-Jiun Jeng11Department of Biochemistry and Molecular Biology, 2Department of Pharmacology and Toxicology, Univ of Texas Medical Branch, Galveston, TX, USAAbstract: Gender and sex hormones can influence a variety of mental health states, including mood, cognitive development and function, and vulnerability to neurodegenerative diseases and brain damage. Functions of neuronal cells may be altered by estrogens depending upon the availability of different physiological estrogenic ligands; these ligands and their effects vary with life stages, the genetic or postgenetic regulation of receptor levels in specific tissues, or the intercession of competing nonphysiological ligands (either intentional or unintentional, beneficial to health or not. Here we review evidence for how different estrogens (physiological and environmental/dietary, acting via different estrogen receptor subtypes residing in alternative subcellular locations, influence brain functions and behavior. We also discuss the families of receptors and transporters for monoamine neurotransmitters and how they may interact with the estrogenic signaling pathways.Keywords: estrogen receptor α, estrogen receptor β, GPR30, GPER, xenoestrogens, phytoestrogens, transporters, brain function, neurotransmitter receptors

  16. Rapid effects of estrogens on short-term memory: Possible mechanisms.

    Science.gov (United States)

    Paletta, Pietro; Sheppard, Paul A S; Matta, Richard; Ervin, Kelsy S J; Choleris, Elena

    2018-06-01

    Estrogens affect learning and memory through rapid and delayed mechanisms. Here we review studies on rapid effects on short-term memory. Estradiol rapidly improves social and object recognition memory, spatial memory, and social learning when administered systemically. The dorsal hippocampus mediates estrogen rapid facilitation of object, social and spatial short-term memory. The medial amygdala mediates rapid facilitation of social recognition. The three estrogen receptors, α (ERα), β (ERβ) and the G-protein coupled estrogen receptor (GPER) appear to play different roles depending on the task and brain region. Both ERα and GPER agonists rapidly facilitate short-term social and object recognition and spatial memory when administered systemically or into the dorsal hippocampus and facilitate social recognition in the medial amygdala. Conversely, only GPER can facilitate social learning after systemic treatment and an ERβ agonist only rapidly improved short-term spatial memory when given systemically or into the hippocampus, but also facilitates social recognition in the medial amygdala. Investigations into the mechanisms behind estrogens' rapid effects on short term memory showed an involvement of the extracellular signal-regulated kinase (ERK) and the phosphoinositide 3-kinase (PI3K) kinase pathways. Recent evidence also showed that estrogens interact with the neuropeptide oxytocin in rapidly facilitating social recognition. Estrogens can increase the production and/or release of oxytocin and other neurotransmitters, such as dopamine and acetylcholine. Therefore, it is possible that estrogens' rapid effects on short-term memory may occur through the regulation of various neurotransmitters, although more research is need on these interactions as well as the mechanisms of estrogens' actions on short-term memory. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. The effects of the botanical estrogen, isoliquiritigenin on delayed spatial alternation.

    Science.gov (United States)

    Kundu, Payel; Neese, Steven L; Bandara, Suren; Monaikul, Supida; Helferich, William G; Doerge, Daniel R; Khan, Ikhlas A; Schantz, Susan L

    Age-related declines in cognitive function can impair working memory, reduce speed of processing, and alter attentional resources. In particular, menopausal women may show an acceleration in the rate of cognitive decline as well as an increased vulnerability to brain diseases as estrogens may play a neuroprotective and neurotrophic role in the brain. To treat menopausal symptoms, many women turn to botanical estrogens that are promoted as a safe and natural alternative to traditional hormone replacement therapy. However, the majority of these compounds have not been systematically evaluated for efficacy and safety. The current study investigated the efficacy of the commercially available botanical estrogenic compound isoliquiritigenin (ISL) to alter performance on an operant working memory task, delayed spatial alternation (DSA). ISL is a compound found in licorice root that has been shown to have a wide range of effects on different biological systems, including estrogenic properties. This botanical is currently being used in over the counter dietary supplements. Middle-aged (12-month old) Long-Evans female rats were ovariectomized and orally dosed with either 0 mg, 6 mg, 12 mg or 24 mg of ISL 60 min before testing on the DSA task. The DSA task required the rat to alternate its responses between two retractable levers in order to earn food rewards. Random delays of 0, 3, 6, 9 or 18 s were imposed between opportunities to press. ISL treatment failed to alter DSA performance. Previous work from our research group has found that estrogenic compounds, including 17β-estradiol and the botanical estrogen genistein impair performance on the DSA task. The goal of our botanical estrogens research is to find compounds that offer some of the beneficial effects of estrogen supplementation, without the harmful effects. This work suggests that ISL may not carry the cognitive risks associated with most other estrogenic compounds tested to date. Copyright © 2018

  18. Effect of Topical Estrogen in the Mangement of Traumatic Facial Wounds

    Directory of Open Access Journals (Sweden)

    Seyed Amirhosein Ghazizadeh Hashemi

    2016-01-01

    Full Text Available Introduction: Acute skin wound healing is a complicated process comprising various phases. Recent animal studies have shown that steroid sex hormones such as estrogen maybe helpful in the regulation of several pathophysiologic stages that are involved in wound healing. In this study we examined the effects of topical estrogen in the treatment of traumatic facial wounds.   Materials and Methods: Patients referred to Luqman Hospital, Tehran with traumatic wounds were enrolled in this case-control study into two groups of equal size. From the second week of the study, topical estrogen (0.625 mg conjugated topical estrogen ointment was administered in the case group, while the control group received a Eucerin dressing only. The two groups were then compared in terms of wound healing rate on Day 7,14, and 30.   Results: Thirty patients with mean age of 16.02+36.23 years were compared in the control and estrogen-treated groups. After treatment, no scars or keloids were observed in either group. The wound area in the estrogen group was lower than that in the control group on Day 14 and 30, but the difference was not significant (P>0.05. Healing rates in the control group on Day  14 (7.1+42.3 vs.50.3+4.9 mm2 and Day 30 (1.9+93.5 vs. + 97.3+0.6 mm2 (were lower than those in the estrogen group, but the differences were not significant (P>0.05. Findings show that the required time for wound healing in the estrogen-treated group was lower than that in the control group, but the difference was not significant (P>0.05.   Conclusion:  Based on this study, topical estrogen has no effect on the rate of wound healing or the rate of wound area .

  19. Effect of Topical Estrogen in the Mangement of Traumatic Facial Wounds

    Science.gov (United States)

    Ghazizadeh Hashemi, Seyed Amirhosein; Barati, Behrooz; Mohammadi, Hosein; Saeidi, Masumeh; Bahreini, Abbas; Kiani, Mohammad Ali

    2016-01-01

    Introduction: Acute skin wound healing is a complicated process comprising various phases. Recent animal studies have shown that steroid sex hormones such as estrogen maybe helpful in the regulation of several pathophysiologic stages that are involved in wound healing. In this study we examined the effects of topical estrogen in the treatment of traumatic facial wounds. Materials and Methods: Patients referred to Luqman Hospital, Tehran with traumatic wounds were enrolled in this case-control study into two groups of equal size. From the second week of the study, topical estrogen (0.625 mg conjugated topical estrogen ointment) was administered in the case group, while the control group received a Eucerin dressing only. The two groups were then compared in terms of wound healing rate on Day 7,14, and 30. Results: Thirty patients with mean age of 16.02+36.23 years were compared in the control and estrogen-treated groups. After treatment, no scars or keloids were observed in either group. The wound area in the estrogen group was lower than that in the control group on Day 14 and 30, but the difference was not significant (P>0.05). Healing rates in the control group on Day 14 (7.1+42.3 vs.50.3+4.9 mm2) and Day 30 (1.9+93.5 vs. + 97.3+0.6 mm2) (were lower than those in the estrogen group, but the differences were not significant (P>0.05). Findings show that the required time for wound healing in the estrogen-treated group was lower than that in the control group, but the difference was not significant (P>0.05). Conclusion: Based on this study, topical estrogen has no effect on the rate of wound healing or the rate of wound area. PMID:26878003

  20. A molecular docking study of phytochemical estrogen mimics from dietary herbal supplements.

    Science.gov (United States)

    Powers, Chelsea N; Setzer, William N

    2015-01-01

    The purpose of this study is to use a molecular docking approach to identify potential estrogen mimics or anti-estrogens in phytochemicals found in popular dietary herbal supplements. In this study, 568 phytochemicals found in 17 of the most popular herbal supplements sold in the United States were built and docked with two isoforms of the estrogen receptor, ERα and ERβ (a total of 27 different protein crystal structures). The docking results revealed six strongly docking compounds in Echinacea, three from milk thistle (Silybum marianum), three from Gingko biloba, one from Sambucus nigra, none from maca (Lepidium meyenii), five from chaste tree (Vitex agnus-castus), two from fenugreek (Trigonella foenum-graecum), and two from Rhodiola rosea. Notably, of the most popular herbal supplements for women, there were numerous compounds that docked strongly with the estrogen receptor: Licorice (Glycyrrhiza glabra) had a total of 26 compounds strongly docking to the estrogen receptor, 15 with wild yam (Dioscorea villosa), 11 from black cohosh (Actaea racemosa), eight from muira puama (Ptychopetalum olacoides or P. uncinatum), eight from red clover (Trifolium pratense), three from damiana (Turnera aphrodisiaca or T. diffusa), and three from dong quai (Angelica sinensis). Of possible concern were the compounds from men's herbal supplements that exhibited strong docking to the estrogen receptor: Gingko biloba had three compounds, gotu kola (Centella asiatica) had two, muira puama (Ptychopetalum olacoides or P. uncinatum) had eight, and Tribulus terrestris had six compounds. This molecular docking study has revealed that almost all popular herbal supplements contain phytochemical components that may bind to the human estrogen receptor and exhibit selective estrogen receptor modulation. As such, these herbal supplements may cause unwanted side effects related to estrogenic activity.