Science.gov

Sample records for estradiol congeners

  1. Estradiol Topical

    MedlinePlus

    ... and large protective caps. Wash your hands with soap and water. To use estradiol emulsion, follow these ... cover it with clothing. Wash your hands with soap and water. Ask your pharmacist or doctor for ...

  2. Atmospheric PCB congeners across Chicago

    PubMed Central

    HU, DINGFEI; LEHMLER, HANS-JOACHIM; MARTINEZ, ANDRES; WANG, KAI; HORNBUCKLE, KERI C.

    2010-01-01

    We have measured PCBs in 184 air samples collected at 37 sites in the city of Chicago using an innovative system of high-volume air samplers mounted on two health clinic vans. Here we describe results of sampling conducted from November 2006 to November 2007. The samples were analyzed for all 209 PCB congeners using a gas chromatograph with tandem mass spectrometry (GC-MS/MS). The ΣPCBs (sum of 169 peaks) in Chicago ranged from 75 pg m−3 to 5500 pg m−3 and primarily varied as a function of temperature. The congener patterns are surprisingly similar throughout the city even though the temperature-corrected concentrations vary by more than an order of magnitude. The average profile resembles a mixture of Aroclor 1242 and Aroclor 1254, and includes many congeners that have been identified as being aryl hydrocarbon receptor (AhR) agonists (dioxin-like) and/or neurotoxins. The toxic equivalence (TEQ) and neurotoxic equivalence (NEQ) in air were calculated and investigated for their spatial distribution throughout the urban-industrial complex of Chicago. The NEQ concentrations are linearly correlated with ΣPCBs while the TEQ concentrations are not predictable. The findings of this study suggest that airborne PCBs in Chicago are widely present and elevated in residential communities; there are multiple sources rather than one or a few locations of very high emissions; the emission includes congeners associated with dioxin-like and neurotoxic effects and congeners associated with unidentified sources. PMID:21918637

  3. The shy prefer familiar congeners.

    PubMed

    Benhaïm, David; Ferrari, Sébastien; Chatain, Béatrice; Bégout, Marie-Laure

    2016-05-01

    The shy-bold continuum is both a fundamental aspect of human behavior and a relatively stable behavioral trait for many other species. Here we assessed whether shy individuals prefer familiar congeners, taking the European sea bass, a recently domesticated fish showing similar behavioral responses to wild fish, as a model to better understand the inter-individual variability in social behavior previously observed in this species. In the wild, the link between familiarity i.e., the preference of fish for familiar congeners and boldness could be part of the mechanism underlying shoaling formation in fish. Thirty fish were individually tested in a device designed to assess the preference for a familiar vs. an unfamiliar congener on the basis of visual cues only. An open field test (OFT) with shelter was performed on the same fish 32 days later to assess the boldness of each individual. Variables of interest included the proportion of time spent in the shelter, border and center zone of the arena and variables of activity. Variables measured in OFT were collapsed into first principal component scores using Principal Components Analysis (PCA) which allowed characterizing a shy-bold continuum. Time spent near the familiar congener was negatively correlated with boldness i.e., shy individuals spent most of the time near the familiar congener. We discuss the relevance of these findings to the understanding of the behavior of European sea bass and suggest that the link between familiarity and shyness is a general aspect of both animal and human behavior.

  4. Atmospheric PCB congeners across Chicago

    NASA Astrophysics Data System (ADS)

    Hu, Dingfei; Lehmler, Hans-Joachim; Martinez, Andres; Wang, Kai; Hornbuckle, Keri C.

    2010-04-01

    We have measured PCBs in 184 air samples collected at 37 sites in the city of Chicago using an innovative system of high-volume air samplers mounted on two health clinic vans. Here we describe results of sampling conducted from November 2006 to November 2007. The samples were analyzed for all 209 PCB congeners using a gas chromatograph with tandem mass spectrometry (GC-MS/MS). The ΣPCBs (sum of 169 peaks) in Chicago ranged from 75 pg m -3 to 5500 pg m -3 and primarily varied as a function of temperature. The congener patterns are surprisingly similar throughout the city even though the temperature-corrected concentrations vary by more than an order of magnitude. The average profile resembles a mixture of Aroclor 1242 and Aroclor 1254, and includes many congeners that have been identified as being aryl hydrocarbon receptor (AhR) agonists (dioxin-like) and/or neurotoxins. The toxic equivalence (TEQ) and neurotoxic equivalence (NEQ) in air were calculated and investigated for their spatial distribution throughout the urban-industrial complex of Chicago. The NEQ concentrations are linearly correlated with ΣPCBs while the TEQ concentrations are not predictable. The findings of this study suggest that airborne PCBs in Chicago are widely present and elevated in residential communities; there are multiple sources rather than one or a few locations of very high emissions; the emission includes congeners associated with dioxin-like or neurotoxic effects and congeners associated with unidentified sources.

  5. Estradiol Transdermal Patch

    MedlinePlus

    ... periods). Transdermal estradiol is also used to prevent osteoporosis (a condition in which the bones become thin ... Women who only need a medication to prevent osteoporosis may benefit more from a different medication that ...

  6. Polychlorinated biphenyl (PCB) effects, PCB congener distributions, and cytochrome P-450 regulation in fish

    SciTech Connect

    Elskus, A.A.

    1992-01-01

    PCB studies were conducted in gonadally mature winter flounder (Pseudopleuronectes americanus) collected from spawning grounds with different degrees of PCB contamination. Flounder from Fox Is., RI, Gaspee Pt., RI and New Bedford, MA (US) had mean hepatic PCB concentrations between 1.6-10.6, 3.8-17.7, and 58-333 {mu}g PCB/g dry liver, respectively. PCB congener distributions in these flounder indicated that PCB disposition was not influenced by reproductive condition, that these migratory fish accumulate a significant portion of their PCB body burden during residence in their spawning grounds, and that flounder selectively metabolize congeners with adjacent meta-, para-unsubstituted carbon atoms. The most significant reproductive effect of PCBs in flounder was a 32 to 52% decrease in the mean ovarian size of highly contaminated females from New Bedford. Plasma levels of the sex hormones, estradiol and testosterone, and of the egg yolk precursor, vitellogenin, as well as hepatic estradiol metabolism (measured as estradiol 2-hydroxylase), showed no relationship to hepatic PCB concentration. PCB effects on flounder P4501A indicated that hepatic PCB concentrations as low as 0.9 {mu}g PCB/g were associated with decreased P4501A catalytic efficiency. Additional suppression of flounder P4501A by estrogens was suggested by depressed levels of P4501A messenger RNA, protein and catalytic activity in highly contaminated female fish with high estradiol titers. The mechanism of P4501A suppression by estrogens was studied in killifish (Fundulus heteroclitus) treated wit {beta}-napthoflavone ({beta}-NF), a P4501A inducer, and/or estradiol.

  7. Estradiol: micrograms or milligrams

    PubMed Central

    Wickramasuriya, Nalin; Shaw, Nicholas J

    2016-01-01

    Summary Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of administration, in the UK oral ethinyl estradiol and the low-dose oral contraceptive pill are commonly used as hormone replacement therapy for practical reasons. We present five peripubertal girls (aged 12.5–14.9 years) with hypogonadism (two with primary hypogonadism due to Turner syndrome and three with central (secondary) hypogonadism as part of multiple pituitary hormone deficiency) who for a variety of reasons have received milligram doses of estradiol (E2) in error for between 6 weeks and 6 months, instead of the expected microgram doses of ethinyl estradiol. Although there are no direct comparisons in peripubertal girls between synthetic and natural estrogens, all girls had vaginal bleeding whilst receiving the milligram doses and have ended up with reduced final heights, below the 9th centile in 1 and below the 2nd centile in 4. Whilst reduction in final height may be part of the underlying condition (especially in Turner syndrome) the two girls with height predictions performed prior to receiving the estrogen overdose have not achieved their predicted height. Estrogen is one of the few drugs which is available in both milligram and microgram formulations. Clinicians need to be alert to the possibility of patients receiving the wrong formulation and dosage in error. Learning points Girls with primary and secondary gonadal failure require assistance with pubertal induction. Although several different formulations and route of administration are available, for practical reasons, the majority of girls in the UK receive oral ethinyl estradiol. Estrogen preparations are available in both milligram and microgram formulations, with potential for receiving the wrong dose. Girls receiving milligram rather than microgram preparations all had vaginal bleeding and a short final height. PMID

  8. Variation in net trophic transfer efficiencies among 21 PCB congeners

    USGS Publications Warehouse

    Madenjian, C.P.; Schmidt, L.J.; Chernyak, S.M.; Elliott, R.F.; Desorcie, T.J.; Quintal, R.T.; Begnoche, L.J.; Hesselberg, R.J.

    1999-01-01

    We tested the hypothesis that the efficiency with which fish retain polychlorinated biphenyl (PCB) congeners from their food strongly depends on Kow and degree of chlorination of the congener. We used diet information, determinations of concentrations of individual PCB congeners in both coho salmon (Oncorhynchus kisutch) and their prey, and bioenergetics modeling to estimate the efficiencies with which Lake Michigan coho salmon retain various PCB congeners from their food. The retention efficiency for the tetrachloro congeners averaged 38%, whereas retention efficiencies for higher chlorinated congeners ranged from 43 to 56%. Not including tetrachloro congeners, we found neither decreasing nor increasing trends in the efficiencies with which the coho salmon retained the PCB congeners from their food with either increasing Kow or increasing degree of chlorination of the PCB congeners. We concluded that (a) for PCB congeners with 5−8 chlorine atoms/molecule, Kow and degree of chlorination had little influence on the efficiency with which coho salmon retained the various PCB congeners in their food, and (b) the efficiency with which coho salmon retained tetrachloro PCB congeners in their food appeared to be slightly lower than that for higher chlorinated PCB congeners.

  9. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  10. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  11. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  12. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  13. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  14. ANALYSIS OF PCB CONGENERS RELATED TO COGNITIVE FUNCTIONING IN ADOLESCENTS

    PubMed Central

    Newman, Joan; Gallo, Mia V.; Schell, Lawrence M.; DeCaprio, Anthony P.; Denham, Melinda; Deane, Glenn D.

    2011-01-01

    To investigate the characteristics of PCBs that are linked to cognitive functioning, those congeners that were concurrently found in 271 Mohawk adolescents were grouped according to structure (dioxin-like or non-dioxin-like) and persistence (persistent or low-persistent). After the effects of the congener groups were orthogonalized, regression analyses (controlling for a number of variables found to be related to the cognitive outcomes) examined the relationship of each congener group to scores on three cognitive tests (the non-verbal Ravens Progressive Matrices, the Test of Memory and Learning, and the Woodcock Johnson – Revised). Five subtests from these cognitive tests were found to be associated with one or more PCB congener groups, most often at a moderate level. Two measures of long term memory (Delayed Recall and Long Term Retrieval) were associated with all four congener groups. Nevertheless, examination of the role of individual congeners in the significantly related congener groups revealed that almost all congeners associated with cognitive outcomes were non-dioxin-like and ortho-substituted. A notable exception was the Ravens test where scores were associated only with dioxin-like congeners. This finding adds to the limited evidence of neurotoxic effects of dioxin-like congeners. Auditory Processing was related only to the persistent congener group. The association of the non-persistent congener group with three cognitive test scores (Delayed Recall, Long Term Retrieval and Comprehension-knowledge) suggests that the Mohawk adolescents have experienced continuing or recent environmental exposure to PCBs that is sufficient to result in detectable cognitive decrements. Comparison of our findings with those of other human studies was limited by the relative lack of specificity of both PCB measures and cognitive outcome measures in much previous work. PMID:19465051

  15. Thrombolysis by thienopyridines and their congeners.

    PubMed

    Gryglewski, R J; Dupin, J P; Uracz, W; Swiês, J; Madej, J; Hou, G; Gravier, D; Casadebaig, F

    2000-12-01

    We propose that anti-platelet thienopyridines, such as ticlopidine or clopidogrel, are thrombolytic owing to endothelial release of prostacyclin (PGI2) and tissue plasminogen activator (t-PA). In this study we used anaesthetised Wistar rats with extracorporal circulation in which arterial blood superfused thrombi which adhered to a strip of collagen. Weight of thrombi was continuously monitored. When administered intravenously, clopidogrel or its R enantiomer deprived of anti-platelet action, both at doses of 3 mg x kg(-1), produced lost in weight of thrombi by 14.1 +/- 1.3% or 16.0 +/- 1.4% (n = 9), and at doses 10 mg x kg(-1) by 28.3 +/- 2.3% or 30.4 +/- 1.9% (n = 8), respectively. Maximum of thrombolysis occurred 30-45 min following the drug administration. Ticlopidine at a dose of 30 mg x kg(-1) reduced weight of thrombi by 33.7 +/- 1.7% (n = 32). Thrombolytic action of ticlopidine was accompanied by a rise in 6!keto-PGF1alpha blood levels from 0.42 +/- 0.10 to 1.58 +/- 0.29 ng x ml(-1) and t-PA antigen plasma levels from 4.70 +/- 1.00 to 12.90 +/- 1.15 ng x ml(-1) (n = 7). Five out of eleven tested thienopyridine congeners with pyrimidine or pyrimidinone instead of pyridine rings had thrombolytic potencies similar to that of clopidogrel (ED30s at a range of 6.2-11.4 mg x kg(-1)). A substantial increase in thrombolytic potency (ED30s at a range of 0.3-2.1 mg x kg(-1)) was observed for congeners in which thienyl ring was condensed with an additional cyclopentyl, cyclohexyl or cycloheptyl structures or in which thienopyridine complex was replaced for a pyridopyrimidine one. We claim that thienopyridines, independently of their delayed anti-platelet action, do produce immediate thrombolysis in vivo. This new activity emulates capacity of their native, non-metabolised molecules to release prostacyclin and tissue plasminogen activator. We have also shown that structural changes in molecules of thienopyridines may intensify their thrombolytic potency.

  16. PCB congener accumulation by periphyton, herbivores, and omnivores.

    PubMed

    Hill, W R; Napolitano, G E

    1997-05-01

    The concentrations of 20 polychlorinated biphenyl (PCB) congeners were measured in periphyton, herbivorous fish (stoneroller minnows, Campostoma anomalum), and omnivorous fish (striped shiners, Luxilus chrysocephalus) in an industrially contaminated stream and a reference stream in eastern Tennessee. The sum of the concentrations of the 20 congeners, normalized by dry mass, was one to two orders of magnitude higher in stonerollers and shiners than in periphyton. Normalizing PCB concentrations by lipid mass reduced concentration differences between periphyton and stonerollers, but PCBs per unit lipid in stonerollers were still 50-350% higher than those in periphyton. Shiners had significantly higher lipid-specific PCB concentrations than did stonerollers, so a trophic hierarchy of primary producer < herbivore < omnivore was evident in lipid-specific PCB concentrations. Differences in lipid type, exposure duration, and exposure sources may account for the trophic-level differences in total PCBs. Congener profiles were roughly similar in periphyton, stonerollers, and shiners: five congeners (IUPAC numbers 101, 110, 138, 153, and 180) constituted >60% of the total mass of PCBs analyzed in all three trophic levels. However, stoneroller and shiner tissue was enriched in congeners 153, 118, and 187 relative to periphyton; congeners 153 and 187 are resistant to metabolic breakdown by monooxygenases found in fish liver. Principal component analysis of congener percentages separated periphyton from fish and distinguished between sampling locations.

  17. Exposure to the three structurally different PCB congeners (PCB 118, 153, and 126) results in decreased protein expression and altered steroidogenesis in the human adrenocortical carcinoma cell line H295R.

    PubMed

    Tremoen, Nina Hårdnes; Fowler, Paul A; Ropstad, Erik; Verhaegen, Steven; Krogenæs, Anette

    2014-01-01

    Polychlorinated biphenyls (PCB), synthetic, persistent organic pollutants (POP), are detected ubiquitously, in water, soil, air, and sediments, as well as in animals and humans. PCB are associated with range of adverse health effects, such as interference with the immune system and nervous system, reproductive abnormalities, fetotoxicity, carcinogenicity, and endocrine disruption. Our objective was to determine the effects of three structurally different PCB congeners, PCB118, PCB 126, and PCB 153, each at two concentrations, on the steroidogenic capacity and proteome of human adrenocortical carcinoma cell line cultures (H295R) . After 48 h of exposure, cell viability was monitored and estradiol, testosterone, cortisol and progesterone secretion measured to quantify steroidogenic capacity of the cells. Two-dimensional (2D) gel-based proteomics was used to screen for proteome alterations in H295R cells in response to the PCB. Exposure to PCB 118 increased estradiol and cortisol secretion, while exposure to PCB 153 elevated estradiol secretion. PCB 126 was the most potent congener, increasing estradiol, cortisol, and progesterone secretion in exposed H295R cells. Seventy-three of the 711 spots analyzed showed a significant difference in normalized spot volumes between controls (vehicle only) and at least one exposure group. Fourteen of these protein spots were identified by liquid chromatography with mass spectroscopy (LC-MS/MS). Exposure to three PCB congeners with different chemical structure perturbed steroidogenesis and protein expression in the H295R in vitro model. This study represents an initial analysis of the effects on proteins and hormones in the H295R cell model, and additional studies are required in order to obtain a more complete understanding of the pathways disturbed by PCB congeners in H295R cells. Overall, alterations in protein regulation and steroid hormone synthesis suggest that exposure to PCB disturbs several cellular processes, including

  18. Facial coloration tracks changes in women's estradiol.

    PubMed

    Jones, Benedict C; Hahn, Amanda C; Fisher, Claire I; Wincenciak, Joanna; Kandrik, Michal; Roberts, S Craig; Little, Anthony C; DeBruine, Lisa M

    2015-06-01

    Red facial coloration is an important social cue in many primate species, including humans. In such species, the vasodilatory effects of estradiol may cause red facial coloration to change systematically during females' ovarian cycle. Although increased red facial coloration during estrus has been observed in female mandrills (Mandrillus sphinx) and rhesus macaques (Macaca mulatta), evidence linking primate facial color changes directly to changes in measured estradiol is lacking. Addressing this issue, we used a longitudinal design to demonstrate that red facial coloration tracks within-subject changes in women's estradiol, but not within-subject changes in women's progesterone or estradiol-to-progesterone ratio. Moreover, the relationship between estradiol and facial redness was observed in two independent samples of women (N = 50 and N = 65). Our results suggest that changes in facial coloration may provide cues of women's fertility and present the first evidence for a direct link between estradiol and female facial redness in a primate species. PMID:25796069

  19. Assimilation efficiency of PBDE congeners in Chinook salmon.

    PubMed

    Dietrich, Joseph P; Strickland, Stacy A; Hutchinson, Greg P; Van Gaest, Ahna L; Krupkin, Alex B; Ylitalo, Gina M; Arkoosh, Mary R

    2015-03-17

    Polybrominated diphenyl ether (PBDE) flame retardants are environmental contaminants that can accumulate in biota. PBDE accumulation in an organism depends on exposure, assimilation efficiency, and elimination/metabolism. Net assimilation efficiency represents the fraction of the contaminant that is retained in the organism after exposure. In the present study, congener-specific estimates of net PBDE assimilation efficiencies were calculated from dietary exposures of juvenile Chinook salmon. The fish were exposed to one to eight PBDE congeners up to 1500 ng total PBDEs/g food. Mean assimilation efficiencies varied from 0.32 to 0.50 for BDE congeners 28, 47, 99, 100, 153, and 154. The assimilation efficiency of BDE49 was significantly greater than 100%, suggesting biotransformation from higher brominated congeners. Whole body concentrations of BDE49 significantly increased with both exposure to increasing concentrations of BDE99 and decreasing fish lipid levels, implying lipid-influenced debromination of BDE99 to BDE49. Excluding BDE49, PBDE assimilation efficiency was not significantly related to the numbers of congeners in the diets, or congener hydrophobicity, but was greater in foods with higher lipid levels. Estimates of PBDE assimilation efficiency can be used in bioaccumulation models to assess threats from PBDE exposure to Chinook salmon health and recovery efforts, as well as to their predators. PMID:25692390

  20. Membrane estradiol signaling in the brain.

    PubMed

    Micevych, Paul; Dominguez, Reymundo

    2009-08-01

    While the physiology of membrane-initiated estradiol signaling in the nervous system has remained elusive, a great deal of progress has been made toward understanding the activation of cell signaling. Membrane-initiated estradiol signaling activates G proteins and their downstream cascades, but the identity of membrane receptors and the proximal signaling mechanism(s) have been more difficult to elucidate. Mounting evidence suggests that classical intracellular estrogen receptor-alpha (ERalpha) and ERbeta are trafficked to the membrane to mediate estradiol cell signaling. Moreover, an interaction of membrane ERalpha and ERbeta with metabotropic glutamate receptors has been identified that explains the pleomorphic actions of membrane-initiated estradiol signaling. This review focuses on the mechanism of actions initiated by membrane estradiol receptors and discusses the role of scaffold proteins and signaling cascades involved in the regulation of nociception, sexual receptivity and the synthesis of neuroprogesterone, an important component in the central nervous system signaling.

  1. 21 CFR 556.240 - Estradiol and related esters.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Estradiol and related esters. 556.240 Section 556... Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol, resulting from the use of estradiol or any of the related esters, are permitted in excess of the...

  2. 21 CFR 556.240 - Estradiol and related esters.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Estradiol and related esters. 556.240 Section 556... Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol, resulting from the use of estradiol or any of the related esters, are permitted in excess of the...

  3. 21 CFR 556.240 - Estradiol and related esters.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Estradiol and related esters. 556.240 Section 556... Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol, resulting from the use of estradiol or any of the related esters, are permitted in excess of the...

  4. 21 CFR 556.240 - Estradiol and related esters.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Estradiol and related esters. 556.240 Section 556... Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol, resulting from the use of estradiol or any of the related esters, are permitted in excess of the...

  5. Estradiol pretreatment attenuated nicotine-induced endothelial cell apoptosis via estradiol functional membrane receptor.

    PubMed

    Wang, Li-li; Zhao, Jian-li; Lau, Wayne-Bond; Zhang, Yan-qing; Qiao, Zhong-dong; Wang, Ya-jing

    2011-06-01

    Cigarette smoking is highly associated with increased cardiovascular disease complications. The female population, however, manifests reduced cardiovascular morbidity. We define nicotine's effect upon human umbilical vein endothelial cells (HUVECs), determine whether estradiol might ameliorate endothelial dysfunction via its membrane estrogen receptor (mER), and attempt to elucidate the underlying mechanisms. Endothelial cells were pretreated with estradiol-BSA and measured resultant ion flux across the cells via the patch clamp technique to assess mER is functionality. Estradiol-BSA administration was associated with 30% decreased nicotine-induced apoptosis and also attenuated nicotine-activated phosphorylation of p38 and ERK. Pretreatment of estradiol-BSA triggered a low calcium influx, suggesting ahead low influx calcium played a critical role in the underlying protective mechanisms of estradiol. Furthermore, this estradiol-BSA protection against apoptosis remained effective in the presence of tamoxifen, an intracellular estrogen receptor (iER) inhibitor. Additionally, tamoxifen did not abolish estradiol-BSA's inhibitory effect upon p38 and ERK's activation, giving evidence to the obligatory role of p38 and ERK signaling in the estradiol-BSA's anti-apoptotic action via mER. Our study provides evidence that nicotine enhances endothelial cell apoptosis, but estrogen exerts anti-apoptotic effect through its functional membrane estrogen receptor. Clinically, the nicotine in cigarettes might contribute to endothelial dysfunction, whereas ambient estradiol may provide cellular protection against nicotine-induced injury through its functional membrane receptor via MAPK pathway downregulation.

  6. Differential toxicity of three PCB congeners in developing sea urchin embryos and implication of TEQ approach

    SciTech Connect

    Schweitzer, L.; Suffet, I.; Hose, J.; Bay, S.

    1995-12-31

    The relationship between body burden and toxicity of three individual PCB congeners in developing sea urchin embryos was investigated to evaluate the validity of current predictive models of PCB toxicity in an invertebrate system. The uptake and accumulation of radiolabeled PCB congeners from sea water was measured in the sea urchin embryo tissues and the relative toxicity determined. According to the toxic equivalents (TEQ) approach of assessing risk to mammals, congener 77, a nonortho-substituted congener, is predicted to be more toxic than the diortho-substituted congeners 47 and 153. Using a 72 hour embryo development assay, congener 47 was found to be at least four times as toxic as congener 77, with EC50s of 15.7 and > 72.5 mmol/kg, respectively. Congener 153, a hexachlorobiphenyl, was virtually nontoxic even at the highest dose used. Cytologic and cytogenetic anomalies were studied to find a possibly more sensitive endpoint and to suggest a mechanism of toxicity. The cytogenetic analysis revealed that the PCBs inhibited mitosis. At the highest doses, complete mitotic arrest was observed. Congener 77 was found to be at least two times more toxic than congener 153 but not as toxic as congener 47 using mitotic activity as the endpoint. Thus, the two endpoints of toxicity did not change the order in which the congeners are toxic, but established different EC50s. The relative toxicities of these congeners in this study contradict the structure-activity prediction of the mammalian-based TEQ approach.

  7. Mechanism of Polybrominated Diphenyl Ether Uptake into the Liver: PBDE Congeners Are Substrates of Human Hepatic OATP Transporters

    PubMed Central

    Pacyniak, Erik; Roth, Megan; Hagenbuch, Bruno; Guo, Grace L.

    2010-01-01

    Polybrominated diphenyl ethers (PBDEs) are flame-retardants that upon chronic exposure enter the liver where they are biotransformed to potentially toxic metabolites. The mechanism by which PBDEs enter the liver is not known. However, due to their large molecular weights (MWs ∼485 to 1000 Da), they cannot enter hepatocytes by simple diffusion. Organic anion–transporting polypeptides (OATPs) are responsible for hepatic uptake of a variety of amphipathic compounds of MWs larger than 350 Da. Therefore, in the present study, Chinese hamster ovary cell lines expressing OATP1B1, OATP1B3, and OATP2B1 were used to test the hypothesis that OATPs expressed in human hepatocytes would be responsible for the uptake of PBDE congeners 47, 99, and 153. The results demonstrated that PBDE congeners inhibited OATP1B1- and OATP1B3-mediated uptake of estradiol-17-β-glucuronide as well as OATP2B1-mediated uptake of estrone-3-sulfate in a concentration-dependent manner. Direct uptake studies confirmed that all three PBDE congeners are substrates for the three tested hepatic OATPs. Detailed kinetic analysis revealed that OATP1B1 transported 2,2′,4,4′-tetrabromodiphenyl ether (BDE47) with the highest affinity (Km = 0.31μM) followed by 2,2′,4,4′,5-pentabromodiphenyl ether (BDE99) (Km = 0.91μM) and 2,2′,4,4′,5,5′-hexabromodiphenyl ether (BDE153) (Km = 1.91μM). For OATP1B3, the order was the same (BDE47: Km = 0.41μM; BDE99: Km = 0.70μM; BDE153: Km = 1.66μM), while OATP2B1 transported all three congeners with similar affinities (BDE47: Km = 0.81μM; BDE99: Km = 0.87μM; BDE153: Km = 0.65μM). These results clearly suggest that uptake of PBDEs via these OATPs is a mechanism responsible for liver-specific accumulation of PBDEs. PMID:20176623

  8. Biomechanical properties of osteoporotic rat femurs after different hormonal treatments: genistein, estradiol, and estradiol/progesterone

    PubMed Central

    Azboy, İbrahim; Özkaya, Mustafa; Demir, Teyfik; Demirtaş, Abdullah; Kağan Arslan, Arslan; Özkul, Emin; Akcan, Adnan; Tolunay, Tolga

    2016-01-01

    Introduction: The purpose of the study is to compare the effects of genistein, estradiol, estradiol/progesterone combination on the bone mineral density and biomechanical properties of ovariectomized rats’ bone. Methods: 50 female adult Sprague-Dawley rats were divided into five groups. Bilaterally ovaeriectomy were performed in all groups except the sham-operated group. Groups were a sham-operated group and a control group (water was given), estradiol treated group (17-β estradiol 0.015 mg/kg per day), genistein treated group (genistein 10 mg/kg per day), and an estradiol/progesterone combination group (17-β estradiol 0.015 mg/kg plus drosperinone 0.028 mg/kg per day). The water or hormones were implemented in relevant groups for eight weeks by orogasthric catheter. The bone mineral density and biomechanical properties of the femur were analyzed. Results: Genistein, estradiol, and estradiol/progesterone groups increased bone mineral density significantly compared to the control group. In diaphysis and metaphysis bending test, all groups had higher peak load values than the control group. There were statistically significant differences between the estrogen/progesterone group and control group in diaphysis bending with regard to peak load. There were statistically significant differences between the estradiol and control groups in metaphysis bending with regard to peak load. In axial rotation test, all groups had higher peak torque values than the control groups. Conclusions: Genistein, estradiol and estrogen/progesterone combination improved the biomechanical properties of the ovariectomized rat bone. Genistein which has less side effects may be considered as an alternative in the treatment of postmenopausal osteoporosis. PMID:27194109

  9. Inhibitory effects of whisky congeners on melanogenesis in mouse B16 melanoma cells.

    PubMed

    Ohguchi, Kenji; Koike, Minako; Suwa, Yoshihide; Koshimizu, Seiichi; Mizutani, Yuki; Nozawa, Yoshinori; Akao, Yukihiro

    2008-04-01

    We examined the effect of whisky congeners, substances other than ethanol in whisky, on melanogenesis in mouse B16 melanoma cells. Treatment with whisky congeners significantly blocked melanogenesis. Our results indicate that the inhibitory effects of whisky congeners on melanogenesis is due to direct inhibition of tyrosinase activity and to suppression of tyrosinase protein levels.

  10. PCB congeners in tissues of European otter (Lutra lutra)

    SciTech Connect

    Mason, C.F.; Ratford, J.R. )

    1994-10-01

    Otters (Lutra lutra) have declined over much of their European range during the past forty years and are now absent from large areas of the lowlands of Western Europe. The most likely cause of the decline is the effects of bioaccumulating contaminants, organochlorine pesticides and PCBs having been implicated. There have been several recent studies of organochlorine residues (pesticides and PCBs) in otter tissues and scats have been used to monitor residues in otter populations. However, only from The Netherlands have data on individual PCB congeners in otter tissues and scats been reported; this Dutch otter population is now extirpated. We report a survey of PCB congeners in samples of tissues and scats from several populations of otters. 21 refs., 3 tabs.

  11. Serum PCB levels and congener profiles among US construction workers

    PubMed Central

    Herrick, Robert F; Meeker, John D; Hauser, Russ; Altshul, Larisa; Weymouth, George A

    2007-01-01

    Background The presence of PCB in caulking (sealant) material found in masonry buildings has been well-documented in several countries. A recent investigation of 24 buildings in the greater Boston area found that 8 buildings had high PCB levels in caulking materials used around window frames and in joints between masonry blocks. Workers removing caulking material have been shown to have elevated serum PCB levels. Methods This project compared serum PCB levels among male workers who installed and/or removed PCB-containing caulking material from buildings in the greater Boston area with reference serum PCB levels from 358 men from the same area. Serum PCB levels were measured in the same laboratory by liquid-liquid extraction, column chromatography clean-up and dual capillary column GC/microECD analysis. Results When the congener profiles were compared between the reference population and the construction workers, the serum levels of the more volatile, lighter PCBs (di-, tri-and tetrachloro, sum of IUPAC# 6–74) were substantially higher among the construction workers. One of the youngest workers had the lowest total serum PCB levels (sum of 57 congeners) of all 6 workers, but the contribution of more volatile (less chlorinated) PCB congeners (#16, 26,28,33,74,66, and 60) was markedly higher than in other 5 workers and reference men. Only this worker was working on a job that involved removing PCB caulking at the time of the blood sampling. Conclusion While the results of this pilot study are based upon small numbers (6 construction workers who handled PCB caulking), the serum PCB levels among the construction workers exceed the referents. Comparison of the congener profiles suggests that there are substantial differences between the construction workers and the general population samples. These differences, and the similarities of profiles among the construction workers strongly suggest that occupational contact with caulking material can be a major source of PCB

  12. Nitric oxide and its congeners in mitochondria: implications for apoptosis.

    PubMed Central

    Richter, C

    1998-01-01

    Apoptosis is an evolutionarily conserved form of physiologic cell death important for tissue development and homeostasis. The causes and execution mechanisms of apoptosis are not completely understood. Nitric oxide (NO) and its congeners, oxidative stress, Ca2+, proteases, nucleases, and mitochondria are considered mediators of apoptosis. Recent findings strongly suggest that mitochondria contain a factor or factors that upon release from the destabilized organelles, induce apoptosis. We have found that oxidative stress-induced release of Ca2+ from mitochondria followed by Ca2+ reuptake (Ca2+ cycling) causes destabilization of mitochondria and apoptosis. The protein product of the protooncogene bcl-2 protects mitochondria and thereby prevents apoptosis. We have also found that NO and its congeners can induce Ca2+ release from mitochondria. Thus, nitrogen monoxide (.NO) binds to cytochrome oxidase, blocks respiration, and thereby causes mitochondrial deenergization and Ca2+ release. Peroxynitrite (ONOO-), on the other hand, causes Ca2+ release from mitochondria by stimulating a specific Ca2+ release pathway. This pathway requires oxidized nicotinamide adenine dinucleotide (NAD+) hydrolysis to adenosine diphosphate ribose and nicotinamide. NAD+ hydrolysis is only possible when some vicinal thiols are cross-linked. ONOO- is able to oxidize them. Our findings suggest that NO and its congeners can induce apoptosis by destabilizing mitochondria via deenergization and/or by inducing a specific Ca2+ release followed by Ca2+ cycling. PMID:9788886

  13. Bioaccumulation of toxaphene congeners in the lake superior food web

    USGS Publications Warehouse

    Muir, D.C.G.; Whittle, D.M.; De Vault, D. S.; Bronte, C.R.; Karlsson, H.; Backus, S.; Teixeira, C.

    2004-01-01

    The bioaccumulation and biotransformation of toxaphene was examined in the food webs of Lake Superior and Siskiwit Lake (Isle Royale) using congener specific analysis as well as stable isotope ratios of carbon and nitrogen to characterize food webs. Toxaphene concentrations (calculated using technical toxaphene) in lake trout (Salvelinus namaycush) from the western basin of Lake Superior (N = 95) averaged (±SD) 889 ± 896 ng/g wet wt and 60 ± 34 ng/g wet wt in Siskiwit Lake. Major congeners in lake trout were B8-789 (P38), B8-2226 (P44), B9-1679 (P50), and B9-1025 (P62). Toxaphene concentrations were found to vary seasonally, especially in lower food web organisms in Lake Superior and to a lesser extent in Siskiwit Lake. Toxaphene concentrations declined significantly in lake herring (Coregonus artedii), rainbow smelt (Omerus mordax), and slimy sculpin (Cottus cognatus) as well as in zooplankton (> 102 &mn;m) and Mysis (Mysis relicta) between May and October. The seasonal variation may reflect seasonal shifts in the species abundance within the zooplankton community. Trophic magnification factors (TMF) derived from regressions of toxaphene congener concentrations versus δ15N were > 1 for most octa- and nonachlorobornanes in Lake Superior except B8-1413 (P26) and B9-715. Log bioaccumulation factors (BAFs) for toxaphene congeners in lake trout (ng/g lipid/ng/L dissolved) ranged from 4.54 to 9.7 and were significantly correlated with log octanol-water partition coefficients. TMFs observed for total toxaphene and congener B9-1679 in Lake Superior were similar to those in Arctic lakes, as well as to previous studies in the Great Lakes, which suggests that the bioaccumulation behavior of toxaphene is similar in pelagic food webs of large, cold water systems. However, toxaphene concentrations were lower in lake trout from Siskiwit Lake and lakes in northwestern Ontario than in Lake Superior possibly because of shorter food chains and greater reliance on zooplankton or

  14. Mimicking of Estradiol Binding by Flame Retardants and Their Metabolites: A Crystallographic Analysis

    PubMed Central

    Gosavi, Rajendrakumar A.; Knudsen, Gabriel A.; Birnbaum, Linda S.

    2013-01-01

    Background: Brominated flame retardants (BFRs), used in many types of consumer goods, are being studied because of concerns about possible health effects related to endocrine disruption, immunotoxicity, reproductive toxicity, and neurotoxicity. Tetrabromobisphenol A (TBBPA), the most widely used BFR, and human metabolites of certain congeners of polybrominated diphenyl ether (e.g., 3-OH-BDE-47) have been suggested to inhibit estrogen sulfotransferase, potentially affecting estrogen metabolism. Objectives: Our primary goal was to understand the structural mechanism for inhibition of the hormone-metabolizing enzyme estrogen sulfotransferase by certain BFRs. We also sought to understand various factors that facilitate the binding of flame retardants in the enzyme binding pocket. Methods: We used X-ray crystallography to obtain atomic detail of the binding modes of TBBPA and 3-OH-BDE-47 to estrogen sulfotransferase for comparison with binding of the endogenous substrate estradiol. Results: The crystal structures reveal how BFRs mimic estradiol binding as well as the various interactions between the compounds and protein residues that facilitate its binding. In addition, the structures provide insights into the ability of the sulfotransferase substrate binding pocket to accommodate a range of halogenated compounds that satisfy minimal structural criteria. Conclusions: Our results show how BFRs or their metabolites can bind to and inhibit a key hormone-metabolizing enzyme, potentially causing endocrine disruption. Citation: Gosavi RA, Knudsen GA, Birnbaum LS, Pedersen LC. 2013. Mimicking of estradiol binding by flame retardants and their metabolites: a crystallographic analysis. Environ Health Perspect 121:1194–1199; http://dx.doi.org/10.1289/ehp.1306902 PMID:23959441

  15. Testosterone and estradiol in juvenile nasopharyngeal angiofibroma tissue.

    PubMed

    Kumagami, H

    1991-01-01

    Five cases of juvenile nasopharyngeal angiofibroma (JNA) were studied in terms of the presence of testosterone and estradiol in the JNA tissues using the peroxidase-antiperoxidase method. Testosterone was found to be negative and estradiol positive in all cases. JNA is considered to be a tumor associated with estradiol.

  16. Inhibition of Estradiol Synthesis Impairs Fear Extinction in Male Rats

    ERIC Educational Resources Information Center

    Graham, Bronwyn M.; Milad, Mohammed R.

    2014-01-01

    Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole,…

  17. EFFECTS OF 17B ESTRADIOL AND ETHINYL ESTRADIOL ON REPRODUCTIVE INDICATORS IN LABORATORY-EXPOSED CUNNER, TAUTOGOLABRUS ADPERSUS

    EPA Science Inventory

    Cunner (Tautogolabrus adspersus) are being studied in our laboratory to evaluate how 17 - estradiol and ethinyl estradiol affect their reproductive success. Cunner was selected because this species spawns daily, is common in estuarine areas, is easily obtainable, and is amenable ...

  18. Influence of cadmium on PCB congener accumulation in quail

    SciTech Connect

    Leonzio, C.; Marsili, L.; Focardi, S. )

    1992-11-01

    Technological development this century has led to an environmental input of synthetic chemical compounds totally extraneous to natural ecosystems such as Polychlorobiphenyls (PCBs), extensively used in agriculture and industry. These xenobiotics have a high fat/water repartition coefficient, making them easily accumulated by living organisms. Their persistence and low degradability means that they are now present throughout the global ecosystem. Ubiquitous environmental contaminants also include heavy metals like Hg, As, Pb, Cd and Cr, of which Cd, an element causing functional damage to the kidney and liver in which it preferentially accumulates, is of special ecotoxicological importance. The WHO has defined an accumulation of 60 mg/kg (fresh weight), beyond which damage occurs. Cd occurs [open quotes]naturally[close quotes] in high concentrations in certain animal species including molluscs. Birds and marine mammals feeding largely on cephalopods show high levels of this metal. Many monitoring studies have also revealed high concentrations of PCBs in the same animals. The vast majority of studies on contaminants in experimental animals consider the short-, medium- and long-term effects of a single pollutant. However, the presence of synergisms and antagonisms between compounds makes it necessary to adopt a more holistic approach to the problem of environmental pollution. In order to understand if the effect of xenobiotic compounds like PCBs may be potentiated by the natural presence of cadmium in bird population, we sought preliminary information on how the presence of cadmium in the diet may influence the accumulation and metabolization of PCB congeners. The influence of Cd on PCB accumulation was investigated in Japanese quail treated experimentally with Cd and PCBs. Particular attention was paid to final congener accumulation and qualitative differences in congener composition between controls and treated birds. 15 refs., 3 figs., 1 tab.

  19. Stepping backward to improve assessment of PCB congener toxicities.

    PubMed Central

    Hansen, L G

    1998-01-01

    Polychlorinated biphenyls (PCBs) are ubiquitous global contaminants that have been intensively investigated for three decades. They are broad-acting toxicants occurring in complex mixtures and accurate risk assessment has proven to be elusive. Focusing on a limited set of end points and emphasizing a fixed set of congeners have led to more streamlined data sets that are meant to expedite hazard characterization and risk assessment for the most potent congeners--aryl hydrocarbon receptor (AhR) agonists. Unfortunately, this has made it impossible to confirm or deny significant contributions from the more prevalent components of the mixtures. PCBs may be only coincidentally present, rather than causal, in some diseases. Still, attempts to determine associations with incomplete residue data may lead to erroneous conclusions and make accurate risk assessment even more elusive. Responses not mediated through the AhR are presented and emphasize large data gaps. Dissimilar analytical reports emphasize that selection of analytes is not consistent. Collectively, these data confirm that AhR-focused objectives unintentionally created the impression that nonplanar PCBs have little if any potential for hazards to humans and wildlife. Near steady-state exposure of healthy adults are probably of minor consequence except for emerging correlations with non-Hodgkin's lymphoma; however, pulses of exposure to more labile mixtures may contribute to developmental effects without leaving a residue record. More broadly based criteria are suggested and harmonization of data collection and presentation are desirable. A more comprehensive list of PCB congeners is proposed that would provide more adequate data upon which to base associations with adverse outcomes. PMID:9539012

  20. Functionalized Congeners of P2Y1 Receptor Antagonists:

    SciTech Connect

    de Castro, Sonia; Maruoka, Hiroshi; Hong, Kunlun; Kilbey, II, S Michael; Costanzi, Stefano; Hechler, Béatrice; Gachet, Christian; Harden, T. Kendall; Jacobson, Kenneth A.

    2010-01-01

    The P2Y{sub 1} receptor is a prothrombotic G protein-coupled receptor (GPCR) activated by ADP. Preference for the North (N) ring conformation of the ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of the P2Y{sub 1} receptor was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute. A series of covalently linkable N{sup 6}-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphates containing extended 2-alkynyl chains was designed, and binding affinity at the human (h) P2Y{sub 1} receptor determined. The chain of these functionalized congeners contained hydrophilic moieties, a reactive substituent, or biotin, linked via an amide. Variation of the chain length and position of an intermediate amide group revealed high affinity of carboxylic congener 8 (K{sub i} 23 nM) and extended amine congener 15 (K{sub i} 132 nM), both having a 2-(1-pentynoyl) group. A biotin conjugate 18 containing an extended {epsilon}-aminocaproyl spacer chain exhibited higher affinity than a shorter biotinylated analogue. Alternatively, click coupling of terminal alkynes of homologous 2-dialkynyl nucleotide derivatives to alkyl azido groups produced triazole derivatives that bound to the P2Y{sub 1} receptor following deprotection of the bisphosphate groups. The preservation of receptor affinity of the functionalized congeners was consistent with new P2Y{sub 1} receptor modeling and ligand docking. Attempted P2Y{sub 1} antagonist conjugation to PAMAM dendrimer carriers by amide formation or palladium-catalyzed reaction between an alkyne on the dendrimer and a 2-iodopurine-derivatized nucleotide was unsuccessful. A dialkynyl intermediate containing the chain length favored in receptor binding was conjugated to an azide-derivatized dendrimer, and the conjugate inhibited ADP-promoted human platelet aggregation. This is the first example of attaching a strategically functionalized P2Y receptor antagonist to a PAMAM dendrimer to

  1. Coplanar and non-coplanar congener-specificity of PCB bioaccumulation and immunotoxicity in sea stars.

    PubMed

    Danis, Bruno; Cattini, Chantal; Teyssié, Jean-Louis; Villeneuve, Jean-Pierre; Fowler, Scott W; Warnau, Michel

    2006-08-23

    The sea star Asterias rubens (L.), a representative species of the North Sea benthic environment, was exposed to a mixture of 10 selected PCB congeners (3 coplanar or c-PCBs, and 7 non-coplanar) via experimentally contaminated sediments. Both the degree of bioaccumulation and subsequent immunotoxic effects of these PCBs were determined. A strong congener-specificity for both bioaccumulation and immunotoxicity was found as well as a probable induction of a congener-specific detoxification mechanism resulting in the dramatic decrease in body levels of the three coplanar congeners tested (PCBs 77, 126 and 169). Moreover, a correlation was found between the bioaccumulation of c-PCBs and their immunotoxic effects. These findings suggest that coplanar congeners should be included in the list of congeners recommended to be analyzed for biological impact-oriented marine monitoring programmes.

  2. Incubation stage and polychlorinated biphenyl (PCB) congener patterns in an altricial and precocial bird species

    USGS Publications Warehouse

    Custer, Christine M.; Custer, Thomas W.; Thyen, Stefan; Becker, Peter H.

    2014-01-01

    The composition of polychlorinated biphenyl (PCB) congeners was compared between non-incubated and embryonated eggs of tree swallows (Tachycineta bicolor) and little terns (Sterna albifrons) to determine if measurable changes in PCB congeners occurred during the embryonic period. There was no indication of changes in PCB congener patterns over the incubation period in tree swallows in 1999 and 2000 at a site with very high PCB exposure or a site with more modest PCB exposure. Additionally, congeners known to be either quickly metabolized or conserved based on experimental studies did not generally respond as predicted. Similarly, PCB congener patterns in eggs of little terns from Bottsand, Schleswig-Holstein, Germany, did not differ between non-incubated and embryonated eggs. The results from both species suggest that the stage of incubation is not an important consideration when evaluating PCB congener patterns; comparisons and assessments can be made with eggs collected at all stages of incubation.

  3. 40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only...

  4. 40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only...

  5. 40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only...

  6. 40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only...

  7. 40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only...

  8. Congenic mice: cutting tools for complex immune disorders.

    PubMed

    Rogner, Ute C; Avner, Philip

    2003-03-01

    Autoimmune diseases are, in general, under complex genetic control and subject to strong interactions between genetics and the environment. Greater knowledge of the underlying genetics will provide immunologists with a framework for study of the immune dysregulation that occurs in such diseases. Ascertaining the number of genes that are involved and their characterization have, however, proven to be difficult. Improved methods of genetic analysis and the availability of a draft sequence of the complete mouse genome have markedly improved the outlook for such research, and they have emphasized the advantages of mice as a model system. In this review, we provide an overview of the genetic analysis of autoimmune diseases and of the crucial role of congenic and consomic mouse strains in such research.

  9. Differences in learning between hyperprolinemic mice and their congenic controls.

    PubMed

    Davis, J L; Pico, R M; Flood, J F

    1987-07-01

    These experiments expanded earlier work on hyperprolinemic mice which showed learning deficits. The following behavioral tasks were used: step-through, passive avoidance; T-maze acquisition; shuttlebox acquisition, and radial-arm maze. Mouse species included PRO/Re-bb (genetically hyperprolinemic mice) and PRO/Re-aa (congenic nonhyperprolinemic controls) obtained from the Jackson Breeding Laboratories. Hyperprolinemic mice were impaired in acquiring T-maze and shuttlebox footshock avoidance behavior. One-trial passive avoidance behavior did not clearly differentiate between the groups. Radial maze performance was poor in both groups due possibly to observed acrophobia and lack of exploratory behavior. The results of this study combined with previously published work suggest that high-brain proline in conjunction with other amino acid changes account for the learning deficits.

  10. Total PCBs and PCB congeners in Spanish Imperial Eagle eggs

    SciTech Connect

    Hernandez, L.M.; Fernandez, M.A.; Gonzalez, M.J. )

    1989-11-01

    The Spanish Imperial Eagle Aquila (heliaca) adalberti is the only directly endangered bird of prey in Europe. Lowered reproductive success in numerous bird species has been associated with eggshell thinning and reduced production caused by DDE, the most common organochlorine residue found in wild birds. Polychlorinated biphenyls (PCBs) are usually the second most common organochlorine pollutant found in wild birds. Research to evaluate the incidence of organochlorine pollutants in the Spanish Imperial Eagle has been previously conducted. The authors have now determined the levels of total PCBs and selected PCB congeners in 34 eggs of Spanish Imperial Eagle collected at Donana National Park, Castile Plateau and Nature Park of Monfrague, since this has considerable significance when attempts are made to correlate the embryonic mortality of avian wildlife with PCB residue levels.

  11. Congener pattern of hexabromobiphenyls in marine biota from different proveniences.

    PubMed

    von der Recke, Roland; Vetter, Walter

    2008-04-15

    Blubber of seals, harbour porpoises and fish originating from the North Sea, the Baltic Sea, as well as coastal waters of Iceland and North America were analyzed for residues of polybrominated biphenyls. According to GC/ECNI-MS, hexabromobiphenyls (hexaBBs) dominated in the samples, followed by pentabromobiphenyls (pentaBBs) and heptabromobiphenyls (heptaBBs), whereas octabromobiphenyls (octaBBs) were only detected in selected samples and nonabromobiphenyls (nonaBBs) and PBB 209 were not found at all. Eleven peaks of hexaBBs -- two peaks might have been each composed of two congeners, respectively -- were detected in the different samples. The hexaBB pattern in samples of Iceland was a mixture of the pattern determined in samples from North America and continental Europe. In samples from the European continent, the major congener in technical hexabromobiphenyl, PBB 153, accounted for 11-37% of the hexaBBs. Other prominent isomers were PBB 155 (7.1-64%) and PBB 154 (11-33%), followed by PBB 133 as well as PBB 132 and/or PBB 146. Most of these PBBs were determined for the first time in marine biota and must be metabolites of higher brominated PBBs since they were not present in any technical product. PBB 153 was dominant in blubber of marine mammals from North America (92-96%). Blubber of harbour porpoises and also seal milk showed more peaks, which is indicative of a lower capability of biotransforming PBBs. It is concluded from this and other studies that PBB residues in North America are mainly originating from technical hexabromobiphenyl, while the bulk of the PBB residues in the European marine samples originated from technical octa- and decabromobiphenyl. Finally, it is evident from this study that a global ban of PBBs should not only be restricted to hexabromobiphenyls, but also needs to include higher brominated mixtures. PMID:18255122

  12. Polybrominated diphenyl ether congener (BDE-100) induces mitochondrial impairment.

    PubMed

    Pereira, Lílian Cristina; de Souza, Alecsandra Oliveira; Dorta, Daniel Junqueira

    2013-06-01

    Brominated flame retardants are used in various consumer products to increase their resistance to fire and/or high temperatures. Polybrominated diphenyl ethers (PBDEs) are representatives of this class and among the most widely used congeners, and BDE-100 is produced on a large scale. There is a lack of toxicological data about these compounds, which has recently become a matter of concern to the scientific community. The mitochondria are recognized as the main energy-producing organelles, as well as playing a vital role in the maintenance of many cell functions. Therefore, mitochondria were used in the present work as an experimental model to evaluate the effects of the BDE-100 congeners at concentrations ranging from 0.1 μM to 50 μM. The results showed that high concentrations of BDE-100 were able to induce mitochondrial alterations. It was observed that the substance had an affinity for the hydrophilic portion of the mitochondrial membrane, as monitored by ANS, inhibiting the glutamate + malate-stimulated mitochondrial respiration and also inducing dissipation of the mitochondrial membrane potential, deregulation of calcium homoeostasis and mitochondrial swelling, the latter being insensitive to cyclosporin A (CsA) but partially inhibited by Ruthenium Red and N-ethyl maleimide. In addition, a significant reduction in mitochondrial ATP content was found, but on the other hand, no oxidative stress was observed after exposure of the mitochondria to BDE-100. These results show the key role of mitochondria in the cytotoxicity induced by BDE-100.

  13. Polybrominated diphenyl ether congener (BDE-100) induces mitochondrial impairment.

    PubMed

    Pereira, Lílian Cristina; de Souza, Alecsandra Oliveira; Dorta, Daniel Junqueira

    2013-06-01

    Brominated flame retardants are used in various consumer products to increase their resistance to fire and/or high temperatures. Polybrominated diphenyl ethers (PBDEs) are representatives of this class and among the most widely used congeners, and BDE-100 is produced on a large scale. There is a lack of toxicological data about these compounds, which has recently become a matter of concern to the scientific community. The mitochondria are recognized as the main energy-producing organelles, as well as playing a vital role in the maintenance of many cell functions. Therefore, mitochondria were used in the present work as an experimental model to evaluate the effects of the BDE-100 congeners at concentrations ranging from 0.1 μM to 50 μM. The results showed that high concentrations of BDE-100 were able to induce mitochondrial alterations. It was observed that the substance had an affinity for the hydrophilic portion of the mitochondrial membrane, as monitored by ANS, inhibiting the glutamate + malate-stimulated mitochondrial respiration and also inducing dissipation of the mitochondrial membrane potential, deregulation of calcium homoeostasis and mitochondrial swelling, the latter being insensitive to cyclosporin A (CsA) but partially inhibited by Ruthenium Red and N-ethyl maleimide. In addition, a significant reduction in mitochondrial ATP content was found, but on the other hand, no oxidative stress was observed after exposure of the mitochondria to BDE-100. These results show the key role of mitochondria in the cytotoxicity induced by BDE-100. PMID:23302053

  14. Patterns of bioaccumulation of polybrominated diphenyl ether and polychlorinated biphenyl congeners in marine mussels.

    PubMed

    Debruyn, Adrian M H; Meloche, Lizanne M; Lowe, Christopher J

    2009-05-15

    Marine mussels (Modiolus modiolus) and sediment from 14 stations near a municipal outfall and three reference locations were analyzed for polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) to evaluate and compare patterns of bioaccumulation of individual congeners between these two groups of chemicals. Of the 47 PBDEs and 209 PCBs analyzed, 34 PBDE and 153 PCB congeners or coeluting groups of congeners were detected in one or more matrices. The predominant PBDE congeners were BDEs 47, 99, 100, and 209, accounting for 80-90% of the total PBDEs in all matrices. PCBs and PBDEs exhibited a parabolic relationship of the biota-sediment accumulation factor (BSAF) versus the log octanol-water partition coefficient(Kow). Below Kow 10(5.5), BSAFs ranged between 1 and 3, reflecting approximate equilibrium between mussels and sedimentforthese relatively water soluble congeners. BSAFs increased with increasing Kow to maximum values of approximately 30-100 for congeners with Kow approximately 10(7) and then declined at higher Kow to a value of approximately 1 for BDE 209. BSAFs for PBDEs were generally 2- to 3-fold higher than those for PCBs of a similar Kow. The calculated BSAFs for PBDE congeners indicate that PBDEs have a pattern of bioaccumulative behavior in mussels similar to that of the PCBs, and that some PBDE congeners may be more bioaccumulative in mussels than PCBs. PMID:19544876

  15. TOXICOKINETICS OF POLYBROMINATED DIPHENYL ETHER CONGENERS 47, 99, 100, AND 153 IN MICE

    EPA Science Inventory

    The congener profiles of polybrominated diphenyl ethers (PBDEs) in human and wildlife samples are dominated by PBDE congeners 47, 99, 100, 153, and 154; all of which are components of the commercial pentaBDE mixtures commonly used in a variety of flammable consumer products. Ver...

  16. ELECTRONIC ELASTICITY-TOXICITY RELATIONSHIPS FOR POLYCHLORINATED DIBENZO-P-DIOXIN CONGENERS. (R826166)

    EPA Science Inventory

    SCF-MO computations have been performed on tetra- to octa-chlorinated dibenzo-p-dioxin congeners (PCDD) using an MNDO-PM3 Hamiltonian. Qualitative relationships were developed between empirical, international-toxic equivalence factors for PCDD congeners and their relati...

  17. Congener specific biotransformation and bioaccumulation of PCDDs and PCDFs from fly ash in fish

    SciTech Connect

    Sijm, D.T.H.M.; Opperhuizen, A. . Research Inst. of Toxicology, Environmental Chemistry Group); Wever, H. . Dept. of Environmental and Toxicological Chemistry)

    1993-10-01

    Biotransformation may be responsible for the lack of bioaccumulation of a number of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). Goldfish (Carassius auratus) that were exposed to PCDDs and PCDFs, and piperonylbutoxide (PBO) in water bioconcentrated significantly more congeners than goldfish exposed to PCDDs and PCDFs only. Monooxygenase activity, which is responsible for the oxidation of specific PCDD and PCDF congeners in untreated fish, was inhibited by fish treated with PBO. In the PBO-treated group and in the control group, congeners with all lateral positions substituted were found. Congeners that lack chlorine substitution on one or more of the lateral positions substituted were found. Congeners that lack chlorine substitution on one or more of the lateral (2,3,7,8) positions and congeners that have all lateral positions chlorinated were found only in PBO-treated fish. Congeners that have at least one free lateral position were therefore assumed to be biotransformed. There was no relationship between the octanol/water partition coefficient and biotransformed. There was no relationship between the octanol/water partition coefficient and biotransformation of the PCDDs and PCDFs. No limitation of uptake for higher chlorinated PCDD and PCDF congeners was found.

  18. Polychlorinated biphenyl congener distributions in burbot: evidence for a latitude effect.

    PubMed

    Stapanian, Martin A; Madenjian, Charles P; Cott, Peter A; Rediske, Richard R; O'Keefe, James P

    2014-11-01

    The authors compared the distributions of the congeners of polychlorinated biphenyls (PCBs) detected in whole-body samples of burbot (Lota lota) from Great Slave Lake and Lake Erie. Total PCB concentrations in Great Slave Lake burbot were about one-sixtieth of the concentrations in Lake Erie burbot. Burbot from Great Slave Lake contained a higher proportion of lower-chlorinated (2-6 chlorines) congeners than did burbot from Lake Erie; the reverse occurred for more highly chlorinated (7-9 chlorines) congeners. Hexachloro congeners, followed by pentachloro congeners, dominated the proportions of total PCBs in burbot from both lakes. There were no differences between sexes in whole-body samples or between gonad and somatic tissues in the proportions of the 39 congeners and 3 sets of coeluters detected in burbot from Great Slave Lake. In contrast, there were distinct sex differences in congener distributions for older burbot from Lake Erie. The results generally supported a prediction of higher proportions of lower-chlorinated PCB homologs in organisms in remote polar areas. However, the latitudinal effect on PCB congener distribution may be more complex than that portrayed in previous studies.

  19. Polychlorinated biphenyl congener distributions in burbot: evidence for a latitude effect

    USGS Publications Warehouse

    Stapanian, Martin A.; Madenjian, Charles P.; Cott, Peter A.; Rediske, Richard R.; O'Keefe, James P.

    2014-01-01

    We compared the distributions of the congeners of polychlorinated biphenyls (PCBs) detected in whole-body samples of burbot (Lota lota) from Great Slave Lake and Lake Erie. Total PCB concentrations in Great Slave Lake burbot were about 1/60 of the concentrations in Lake Erie burbot. Burbot from Great Slave Lake contained a higher proportion of lower-chlorinated (2-6 chlorines) congeners than did burbot from Lake Erie; the reverse occurred for more highly chlorinated (7-9 chlorines) congeners. Hexachloro congeners, followed by pentachloro congeners, dominated the proportions of total PCB in burbot from both lakes. There were no differences between sexes in whole-body samples or between gonad and somatic tissues in the proportions of the 39 congeners and three sets of co-eluters detected in burbot from Great Slave Lake. In contrast, there were distinct sex differences in congener distributions for older burbot from Lake Erie. Our results generally supported a prediction of higher proportions of lower-chlorinated PCB homologs in organisms in remote polar areas. However, the latitudinal effect on PCB congener distribution may be more complex than that portrayed in previous studies.

  20. The Binding Constant of Estradiol to Bovine Serum Albumin: An Upper-Level Experiment Utilizing Tritium-Labeled Estradiol and Liquid Scintillation Counting

    ERIC Educational Resources Information Center

    Peihong Liang; Adhyaru, Bhavin; Pearson, Wright L.; Williams, Kathryn R.

    2006-01-01

    The experiment used [to the third power]H-labeled estradiol to determine the binding constant of estradiol to bovine serum albumin. Estradiol must complex with serum proteins for the transport in the blood stream because of its low solubility in aqueous systems and estradiol-protein binding constant, where K[subscript B] is important to understand…

  1. Contrasting patterns of transgenerational plasticity in ecologically distinct congeners.

    PubMed

    Sultan, Sonia E; Barton, Kasey; Wilczek, Amity M

    2009-07-01

    Stressful parental environments can influence offspring size and development either adaptively or maladaptively, yet little is known about species' differences in this complex aspect of phenotypic plasticity. We performed a reciprocal split-brood experiment to compare transgenerational plasticity in response to drought stress in two closely related annual plant species. We raised inbred replicate parent plants of eight genotypes per species in dry vs. moist soil to generate offspring of each genetic line that differed only in parental environment, then monitored seedling development in both dry and moist conditions. Individuals of the two species expressed contrasting patterns of transgenerational plasticity for traits important to seedling drought tolerance. In Polygonum persicaria, a weedy generalist found in moist, dry, and variably dry sites, drought-stressed plants produced offspring with longer and more rapidly extending root systems and greater biomass when growing in dry soil. In contrast, in P. hydropiper, a non-weedy congener restricted to moist habitats, the offspring of drought-stressed parents had reduced root system development and seedling biomass in dry soil. In P. persicaria, transgenerational and immediate adaptive plasticity combined to produce drought-adapted seedling phenotypes. These results make clear that characteristic patterns of transgenerational plasticity can contribute to ecological diversity among species.

  2. The development of female sexual behavior requires prepubertal estradiol.

    PubMed

    Brock, Olivier; Baum, Michael J; Bakker, Julie

    2011-04-13

    The classic view of brain and behavioral sexual differentiation holds that the neural mechanisms controlling sexual behavior in female rodents develop in the absence of ovarian sex hormone actions. However, in a previous study, female aromatase knock-out (ArKO) mice, which cannot convert testosterone to estradiol, showed deficient male-oriented partner preference and lordosis behaviors in response to adult ovarian hormones, raising the possibility that estradiol may contribute to the development of these female sexual behaviors. In the present experiments, administering estradiol prepubertally [between postnatal day 15 (P15) and P25] significantly enhanced the ability of ArKO female mice to display lordosis behavior in response to ovarian hormones administered later in adulthood, whereas treatment with estradiol over an earlier postnatal period (P5-P15) had no such effect. Treatment of ArKO females with estradiol between P15 and P25 also rescued their later preference to approach distal cues from an intact male over an estrous female. ArKO females also displayed significantly less female-directed (male-typical) mounting behavior than wild-type control females when treated with testosterone in adulthood. Prepubertal estradiol treatment failed to reverse this deficit in ArKO females, whereas earlier postnatal estradiol augmented later mounting in both genotypes. Our results provide new evidence for an organizing role of prepubertal estradiol in the development of neural mechanisms that control female-typical sexual behavior.

  3. Evidence of latitudinal fractionation of polychlorinated biphenyl congeners along the Baltic Sea region

    SciTech Connect

    Agrell, C.; Okla, L.; Larsson, P.; Backe, C.; Wania, F.

    1999-04-15

    Annual cycles of the atmospheric concentrations of PCBs were determined at 16 (mostly rural) stations around the Baltic Sea between 1990 and 1993. The concentration levels of individual congeners were found to be influenced by their physical-chemical properties, ambient temperature, and geographical location. Median levels of PCBs were similar at all stations except at one urban site near Riga. A latitudinal gradient with higher levels in the south was found for the sum of PCB as well as for individual congeners, and the gradient was more pronounced for the low volatility congeners. As a result, the high volatility congeners increased in relative importance with latitude. Generally, PCB concentrations increased with temperature, but slopes of the partial pressure in air versus reciprocal temperature were different between congeners and between stations. In general, the low volatility congeners were more temperature dependent than the high volatility PCB congeners. Steep slopes at a sampling location indicate that the concentration in air is largely determined by diffusive exchange with soils. Lack of a temperature dependence may be due to the influence of long-range transported air masses at remote sites and due to the episodic or random nature of PCB sources at urban sites.

  4. Bioaccumulation of PCBs in fish in relation to PCB congener distributions in weathered sediments

    SciTech Connect

    Dwyer, R.; Orr, J.; Knorr, D. ||; Wagner, R.

    1995-12-31

    PCBs in the sediments and fish of Lake Hartwell (SC) have been associated with the former operations of a manufacturing facility in Pickens, SC, and have been detected downstream in Twelvemile Creek, and the Twelvemile Creek Arm of Lake Hartwell. Recent efforts have focused on identifying appropriate methods to reduce the long-term health risks due to eating these fish. The present analysis examines the relationship between PCB congener distributions in largemouth bass and hybrid striped bass, and congener distributions in both deep and surficial sediments in the lake. Initial analyses established that penta-, hexa-, and heptachlorine congeners had undergone dechlorination in deep sediments to mono-, di-, tri-, and tetrachlorobiphenyl congeners, probably by anaerobic pathways identified by others. Further, surficial sediments showed the further dechlorination and degradation of these less-chlorinated congeners, and the presence of chlorobenzoate breakdown products of aerobic pathways. The resulting differences in congener distributions in the two sediment strata indicated the sources of PCBs that bioaccumulated in the two fish species. After correcting for lipid partitioning using the octanol-water partition coefficients for 24 major PCB congener peaks, ratios were formed between fish fillet concentrations and concentrations in each of the two sediment strata.

  5. Congener-based analysis of the weathering of PCB Aroclor 1242 in paper mill sludge.

    PubMed

    Saba, Tarek; Boehm, Paul D

    2011-02-01

    Aroclor 1242 contains a high percentage of lightly chlorinated congeners, which makes it susceptible to congener profile alterations as a result of physical-chemical environmental weathering by water washing, evaporation, and volatilization. The analysis of the variability of congener profiles in paper sludge samples using PCA, mixing models, and correlation (R(2)) analysis, provided an integrated description of the behavior of Aroclor 1242 after its release in the environment. The results showed that the total PCB concentration decreased as the sample experienced weathering, with the congener profile of Aroclor 1242 shifting towards resembling heavier Aroclors as lighter congeners were lost. Mixing model analysis confirmed that a sample containing weathered Aroclor 1242 could easily be misidentified by laboratories as containing a mix of heavier Aroclors. The R(2) analysis showed that the profile of the congeners within a homologue group remained the same after weathering. This analysis showed that congeners that belong to the same level of chlorination behave similarly in such a manner that retains their overall profile when exposed to physical weathering.

  6. Differential toxicity of three polychlorinated biphenyl congeners in developing sea urchin embryos

    SciTech Connect

    Schweitzer, L.E.; Suffet, I.H.; Hose, J.E.; Bay, S.M.

    1997-07-01

    The relationship between body burden and toxicity of three individual polychlorinated biphenyl (PCB) congeners in developing sea urchin embryos was investigated to evaluate the validity of current predictive models of PCB toxicity in an invertebrate system. Body burdens of radiolabeled PCB congeners (IUPAC-47, 77, and 153) accumulated from a seawater were used to determine median effective concentrations (EC50s) for developmental and cytogenetic effects following a 72-h exposure. Congener 47, a di-ortho-substituted tetrachlorobiphenyl, was found to be at least four times more toxic than congener 77, a non-ortho-substituted (coplanar) tetrachlorobiphenyl, with EC50s of 47 and >218 mmol/kg, respectively, using an embryo development assay. This result contradicts the structure-activity prediction of the mammalian-based toxic equivalents (TEQs) approach, demonstrating the need for an ecotoxicologic model. Congener 153, a di-ortho-substituted hexachlorobiphenyl, was virtually nontoxic in terms of developmental effects at the highest dose achievable at its limit of water solubility. Cytogenetic analysis was a more sensitive method for assessing toxicity than the embryo development assay. Dose-response relationships were established with mitotic activity being the most sensitive endpoint because the PCBs appeared to inhibit mitosis. At the highest doses, complete mitotic arrest was observed. Congener 77 was found to be at least two times more toxic than congener 153 but not as toxic as congener 47 using mitotic activity as the endpoint for toxicity. Thus, the developmental and cytogenetic endpoints ranked the toxicity of the congeners similarly, but established different EC50s.

  7. Brown Norway Chromosome 1 Congenic Reduces Symptoms of Renal Disease in Fatty Zucker Rats

    PubMed Central

    Warden, Craig H.; Slupsky, Carolyn; Griffey, Stephen M.; Bettaieb, Ahmed; Min, Esther; Le, Anh; Fisler, Janis S.; Hansen, Susan; Haj, Fawaz; Stern, Judith S.

    2014-01-01

    We previously reported that a congenic rat with Brown Norway (BN) alleles on chromosome 1 reduces renal disease of 15-week old fatty Zucker rats (ZUC). Development of renal disease in fatty BN congenic and fatty ZUC rats from 9 through 28 weeks is now examined. Analysis of urine metabolites by 1H nuclear magnetic resonance (NMR) spectroscopy revealed a significantly increased urinary loss of glucose, myo-inositol, urea, creatine, and valine in ZUC. Food intake was lower in the BN congenic rats at weeks 9–24, but they weighed significantly more at 28 weeks compared with the ZUC group. Fasting glucose was significantly higher in ZUC than congenic and adiponectin levels were significantly lower in ZUC, but there was no significant genotype effect on Insulin levels. Glucose tolerance tests exhibited no significant differences between ZUC and congenic when values were normalized to basal glucose levels. Quantitative PCR on livers revealed evidence for higher gluconeogenesis in congenics than ZUC at 9 weeks. Plasma urea nitrogen and creatinine were more than 2-fold higher in 28-week ZUC. Twelve urine protein markers of glomerular, proximal and distal tubule disease were assayed at three ages. Several proteins that indicate glomerular and proximal tubular disease increased with age in both congenic and ZUC. Epidermal growth factor (EGF) level, a marker whose levels decrease with distal tubule disease, was significantly higher in congenics. Quantitative histology of 28 week old animals revealed the most significant genotype effect was for tubular dilation and intratubular protein. The congenic donor region is protective of kidney disease, and effects on Type 2 diabetes are likely limited to fasting glucose and adiponectin. The loss of urea together with a small increase of food intake in ZUC support the hypothesis that nitrogen balance is altered in ZUC from an early age. PMID:24498189

  8. A modeling approach to compare ΣPCB concentrations between congener-specific analyses

    USGS Publications Warehouse

    Gibson, Polly P.; Mills, Marc A.; Kraus, Johanna M.; Walters, David M.

    2016-01-01

    Changes in analytical methods over time pose problems for assessing long-term trends in environmental contamination by polychlorinated biphenyls (PCBs). Congener-specific analyses vary widely in the number and identity of the 209 distinct PCB chemical configurations (congeners) that are quantified, leading to inconsistencies among summed PCB concentrations (ΣPCB) reported by different studies. Here we present a modeling approach using linear regression to compare ΣPCB concentrations derived from different congener-specific analyses measuring different co-eluting groups. The approach can be used to develop a specific conversion model between any two sets of congener-specific analytical data from similar samples (similar matrix and geographic origin). We demonstrate the method by developing a conversion model for an example data set that includes data from two different analytical methods, a low resolution method quantifying 119 congeners and a high resolution method quantifying all 209 congeners. We used the model to show that the 119-congener set captured most (93%) of the total PCB concentration (i.e., Σ209PCB) in sediment and biological samples. ΣPCB concentrations estimated using the model closely matched measured values (mean relative percent difference = 9.6). General applications of the modeling approach include (a) generating comparable ΣPCB concentrations for samples that were analyzed for different congener sets; and (b) estimating the proportional contribution of different congener sets to ΣPCB. This approach may be especially valuable for enabling comparison of long-term remediation monitoring results even as analytical methods change over time. 

  9. DIBROMOACETIC ACID-INDUCED ELEVATIONS OF ESTRADIOL IN THE CYCLING AND OVARIECTOMOZED/ESTRADIOL-IMPLANTED FEMALE RAT

    EPA Science Inventory

    Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations of Estradiol in Both Cycling and Ovariectomized / Estradiol-implanted Female Rats

    ABSTRACT
    Haloacetic acids are one of the principal classes of disinfection by-products generated by the chlorination of mun...

  10. The Identification of Congeners and Aliens by Drosophila Larvae

    PubMed Central

    Del Pino, Francisco; Jara, Claudia; Pino, Luis; Medina-Muñoz, María Cristina; Alvarez, Eduardo; Godoy-Herrera, Raúl

    2015-01-01

    We investigated the role of Drosophila larva olfactory system in identification of congeners and aliens. We discuss the importance of these activities in larva navigation across substrates, and the implications for allocation of space and food among species of similar ecologies. Wild type larvae of cosmopolitan D. melanogaster and endemic D. pavani, which cohabit the same breeding sites, used species-specific volatiles to identify conspecifics and aliens moving toward larvae of their species. D. gaucha larvae, a sibling species of D. pavani that is ecologically isolated from D. melanogaster, did not respond to melanogaster odor cues. Similar to D. pavani larvae, the navigation of pavani female x gaucha male hybrids was influenced by conspecific and alien odors, whereas gaucha female x pavani male hybrid larvae exhibited behavior similar to the D. gaucha parent. The two sibling species exhibited substantial evolutionary divergence in processing the odor inputs necessary to identify conspecifics. Orco (Or83b) mutant larvae of D. melanogaster, which exhibit a loss of sense of smell, did not distinguish conspecific from alien larvae, instead moving across the substrate. Syn97CS and rut larvae of D. melanogaster, which are unable to learn but can smell, moved across the substrate as well. The Orco (Or83b), Syn97CS and rut loci are necessary to orient navigation by D. melanogaster larvae. Individuals of the Trana strain of D. melanogaster did not respond to conspecific and alien larval volatiles and therefore navigated randomly across the substrate. By contrast, larvae of the Til-Til strain used larval volatiles to orient their movement. Natural populations of D. melanogaster may exhibit differences in identification of conspecific and alien larvae. Larval locomotion was not affected by the volatiles. PMID:26313007

  11. The Identification of Congeners and Aliens by Drosophila Larvae.

    PubMed

    Del Pino, Francisco; Jara, Claudia; Pino, Luis; Medina-Muñoz, María Cristina; Alvarez, Eduardo; Godoy-Herrera, Raúl

    2015-01-01

    We investigated the role of Drosophila larva olfactory system in identification of congeners and aliens. We discuss the importance of these activities in larva navigation across substrates, and the implications for allocation of space and food among species of similar ecologies. Wild type larvae of cosmopolitan D. melanogaster and endemic D. pavani, which cohabit the same breeding sites, used species-specific volatiles to identify conspecifics and aliens moving toward larvae of their species. D. gaucha larvae, a sibling species of D. pavani that is ecologically isolated from D. melanogaster, did not respond to melanogaster odor cues. Similar to D. pavani larvae, the navigation of pavani female x gaucha male hybrids was influenced by conspecific and alien odors, whereas gaucha female x pavani male hybrid larvae exhibited behavior similar to the D. gaucha parent. The two sibling species exhibited substantial evolutionary divergence in processing the odor inputs necessary to identify conspecifics. Orco (Or83b) mutant larvae of D. melanogaster, which exhibit a loss of sense of smell, did not distinguish conspecific from alien larvae, instead moving across the substrate. Syn97CS and rut larvae of D. melanogaster, which are unable to learn but can smell, moved across the substrate as well. The Orco (Or83b), Syn97CS and rut loci are necessary to orient navigation by D. melanogaster larvae. Individuals of the Trana strain of D. melanogaster did not respond to conspecific and alien larval volatiles and therefore navigated randomly across the substrate. By contrast, larvae of the Til-Til strain used larval volatiles to orient their movement. Natural populations of D. melanogaster may exhibit differences in identification of conspecific and alien larvae. Larval locomotion was not affected by the volatiles.

  12. The Identification of Congeners and Aliens by Drosophila Larvae.

    PubMed

    Del Pino, Francisco; Jara, Claudia; Pino, Luis; Medina-Muñoz, María Cristina; Alvarez, Eduardo; Godoy-Herrera, Raúl

    2015-01-01

    We investigated the role of Drosophila larva olfactory system in identification of congeners and aliens. We discuss the importance of these activities in larva navigation across substrates, and the implications for allocation of space and food among species of similar ecologies. Wild type larvae of cosmopolitan D. melanogaster and endemic D. pavani, which cohabit the same breeding sites, used species-specific volatiles to identify conspecifics and aliens moving toward larvae of their species. D. gaucha larvae, a sibling species of D. pavani that is ecologically isolated from D. melanogaster, did not respond to melanogaster odor cues. Similar to D. pavani larvae, the navigation of pavani female x gaucha male hybrids was influenced by conspecific and alien odors, whereas gaucha female x pavani male hybrid larvae exhibited behavior similar to the D. gaucha parent. The two sibling species exhibited substantial evolutionary divergence in processing the odor inputs necessary to identify conspecifics. Orco (Or83b) mutant larvae of D. melanogaster, which exhibit a loss of sense of smell, did not distinguish conspecific from alien larvae, instead moving across the substrate. Syn97CS and rut larvae of D. melanogaster, which are unable to learn but can smell, moved across the substrate as well. The Orco (Or83b), Syn97CS and rut loci are necessary to orient navigation by D. melanogaster larvae. Individuals of the Trana strain of D. melanogaster did not respond to conspecific and alien larval volatiles and therefore navigated randomly across the substrate. By contrast, larvae of the Til-Til strain used larval volatiles to orient their movement. Natural populations of D. melanogaster may exhibit differences in identification of conspecific and alien larvae. Larval locomotion was not affected by the volatiles. PMID:26313007

  13. Use of herbarium data to evaluate weediness in five congeners.

    PubMed

    Hanan-A, Ana M; Vibrans, Heike; Cacho, N Ivalú; Villaseñor, José L; Ortiz, Enrique; Gómez-G, Vinicio A

    2015-12-15

    It is often desirable to quantify a plant's relative weediness or synanthropy, that is, the degree to which a species associates with human-caused disturbance, in order to study and understand the biology, ecology and evolution of weeds and invasive plants. Herbarium specimens are among the most accessible and verifiable sources of data on distribution and habitat. However, the habitat distribution of species may not be reflected accurately by herbarium specimen data, due to well-known biases in plant collection. Here, we assess how well herbarium specimens reflect species' weediness, when compared with direct field surveys. We used five species of Melampodium (Asteraceae) and classified their degree of weediness with a modification of Nuorteva's synanthropy index, based on herbarium specimens. We then modelled the distribution of our focal species in Mexico using MaxEnt and identified a polygon of ∼3000 km(2) in the state of Nayarit, Mexico, where there was a high probability of finding all five species. Systematic field searches in the target area documented all visible populations of four species along major and minor roads. Then we, again, classified their degree of weediness with the synanthropy index, based now on field data, and compared. We found that herbarium data were an accurate predictor of a species' weediness relative to its congeners despite the well-documented skew of herbarium data towards natural areas, which our data reflected as well. So, herbarium data can be used to classify species' weediness relative to each other, but not in absolute terms, if the specimens were correctly identified and none of the species were subject to particular collection bias. This study is the first attempt to compare herbarium and field data on this subject and may be relevant for other types of investigations based on herbarium data. Our work also highlights the usefulness of distribution models based on herbarium specimens.

  14. Use of herbarium data to evaluate weediness in five congeners

    PubMed Central

    Hanan-A., Ana M.; Vibrans, Heike; Cacho, N. Ivalú; Villaseñor, José L.; Ortiz, Enrique; Gómez-G., Vinicio A.

    2016-01-01

    It is often desirable to quantify a plant's relative weediness or synanthropy, that is, the degree to which a species associates with human-caused disturbance, in order to study and understand the biology, ecology and evolution of weeds and invasive plants. Herbarium specimens are among the most accessible and verifiable sources of data on distribution and habitat. However, the habitat distribution of species may not be reflected accurately by herbarium specimen data, due to well-known biases in plant collection. Here, we assess how well herbarium specimens reflect species' weediness, when compared with direct field surveys. We used five species of Melampodium (Asteraceae) and classified their degree of weediness with a modification of Nuorteva's synanthropy index, based on herbarium specimens. We then modelled the distribution of our focal species in Mexico using MaxEnt and identified a polygon of ∼3000 km2 in the state of Nayarit, Mexico, where there was a high probability of finding all five species. Systematic field searches in the target area documented all visible populations of four species along major and minor roads. Then we, again, classified their degree of weediness with the synanthropy index, based now on field data, and compared. We found that herbarium data were an accurate predictor of a species' weediness relative to its congeners despite the well-documented skew of herbarium data towards natural areas, which our data reflected as well. So, herbarium data can be used to classify species' weediness relative to each other, but not in absolute terms, if the specimens were correctly identified and none of the species were subject to particular collection bias. This study is the first attempt to compare herbarium and field data on this subject and may be relevant for other types of investigations based on herbarium data. Our work also highlights the usefulness of distribution models based on herbarium specimens. PMID:26672076

  15. Toxic congener-specific analysis of PCBs: assessment of toxicity in equivalents of TCDD

    SciTech Connect

    Olafsson, P.G.; Bryan, A.M.

    1987-01-01

    High resolution capillary gas chromatographic analysis of the polychlorobiphenyls (PCBs) present in snapping turtle eggs, provided quantitative data on selected toxic congeners. The concentrations of these congeners have been converted into equivalent toxic concentrations of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD). The toxic equivalent factors (TEFs), necessary to effect this transformation were derived from EC/sub 50/ values (half the concentration of the toxic congener required to produce the maximum effect) for aryl hydrocarbon hydroxylase (AHH) induction associated with the corresponding toxic PCB congener or isomer. Summation of the resulting toxic equivalents provided a composite assessment of the toxicity of the PCB mixture in terms of an equivalent concentration of TCDD.

  16. The influence of biotransformation on the biomagnification of polychlorobiphenyl congeners in marine mammals and birds

    SciTech Connect

    Boon, J.P.

    1994-12-31

    Results of in-vitro and in-vivo experiments and comparisons of PCB-patterns of prey and predator of field data from the North Sea are presented to explain the influence of biotransformation of PCB congeners on their biomagnification in lung-breathing marine predators. Persistent congeners are taken up proportionally to their relative contribution in prey organisms. Hence molecular descriptors do not play any role here. Metabolizability depends on the presence of vicinal hydrogen atoms and the number of ortho-Cl substituents. The maximum number ortho-Cl atoms still allowing biotransformation differs between seals, cetaceans and seabirds. The majority of congeners with a strong affinity for the Ah-receptor are metabolized in marine mammals, leaving the important question whether the observed effects on reproduction are due to parent compounds or metabolites. Starvation leads to a relative decrease of the metabolizable congeners in the overall pattern.

  17. Nongenomic effects of estradiol on aggression under short day photoperiods

    PubMed Central

    Laredo, Sarah A.; Landeros, Rosalina Villalon; Dooley, James C.; Steinman, Michael Q.; Orr, Veronica; Silva, Andrea L.; Crean, Katie K.; Robles, Cindee F.; Trainor, Brian C.

    2013-01-01

    In several vertebrate species, the effects of estrogens on male aggressive behavior can be modulated by environmental cues. In song sparrows and rodents, estrogens modulate aggression in the nonbreeding season or winter-like short days, respectively. The behavioral effects of estrogens are rapid, which generally is considered indicative of nongenomic processes. The current study further examined the hypothesis that estradiol acts nongenomically under short days by utilizing a protein synthesis inhibitor, cycloheximide (CX). Mice were housed in either short or long day photoperiods, and treated with an aromatase inhibitor. One hour before resident-intruder testing mice were injected with either CX or saline vehicle, and 30 minutes later were treated orally with either cyclodextrin conjugated estradiol or vehicle. Under short days, mice treated with estradiol showed a rapid decrease in aggressive behavior, independent of CX administration. CX alone had no effect on aggression. These results show that protein synthesis is not required for the rapid effects of estradiol on aggression, strongly suggesting that these effects are mediated by nongenomic processes. We also showed that estradiol suppressed c-fosimmunoreactivity in the caudal bed nucleus of the stria terminalis under short days. No effects of estradiol on behavior or c-fos expression were observed in mice housed under long days. Previously we had also demonstrated that cage beddinginfluenced the directional effects of estrogens on aggression. Here, we show that the phenomenon of rapid action of estradiol on aggression under short days is a robust result that generalizes to different bedding conditions. PMID:23763907

  18. Organic anion transporting polypeptides in the hepatic uptake of PBDE congeners in mice

    SciTech Connect

    Pacyniak, Erik; Hagenbuch, Bruno; Klaassen, Curtis D.; Lehman-McKeeman, Lois; Guo, Grace L.

    2011-11-15

    BDE47, BDE99 and BDE153 are the predominant polybrominated diphenyl ether (PBDE) congeners detected in humans and can induce drug metabolizing enzymes in the liver. We have previously demonstrated that several human liver organic anion transporting polypeptides (humans: OATPs; rodents: Oatps) can transport PBDE congeners. Mice are commonly used to study the toxicity of chemicals like the PBDE congeners. However, the mechanism of the hepatic PBDE uptake in mice is not known. Therefore, the purpose of the current study was to test the hypothesis that BDE47, BDE99, and BDE153 are substrates of mouse hepatic Oatps (Oatp1a1, Oatp1a4, Oatp1b2, and Oatp2b1). We used Human Embryonic Kidney 293 (HEK293) cells transiently expressing individual Oatps and quantified the uptake of BDE47, BDE99, and BDE153. Oatp1a4, Oatp1b2, and Oatp2b1 transported all three PBDE congeners, whereas Oatp1a1 did transport none. Kinetic studies demonstrated that Oatp1a4 and Oatp1b2 transported BDE47 with the greatest affinity, followed by BDE99 and BDE153. In contrast, Oatp2b1 transported all three PBDE congeners with similar affinities. The importance of hepatic Oatps for the liver accumulation of BDE47 was confirmed using Oatp1a4-, and Oatp1b2-null mice. -- Highlights: Black-Right-Pointing-Pointer PBDE congeners are substrates of OATPs expressed in human hepatocytes. Black-Right-Pointing-Pointer Mice are commonly used to study the toxicity of chemicals like the PBDE congeners. Black-Right-Pointing-Pointer Oatp1a4, Oatp1b2, and Oatp2b1 transported all three PBDE congeners in vitro. Black-Right-Pointing-Pointer In vivo Oatp1a4 plays a minor and Oatp1b2 a major role in BDE47 liver accumulation.

  19. Accumulation of polychlorobiphenyl congeners and p,p'-DDE at environmental concentrations by corn and beans

    SciTech Connect

    Shane, L.A.; Bush, B.

    1989-02-01

    The uptake of polychlorinated biphenyl (PCB) congeners present at low concentrations in the environment was investigated in leaf composites of four crop species and final fruits at two sites. All four species preferentially accumulated the same eight congeners, although not in the same degree or rank. No bean species demonstrated a significant increase in accumulation over time, and corn significantly reduced its PCB load over time. Mechanisms are suggested for such behavior. Fruits were 100 times less contaminated than plant leaves.

  20. Residual congener pattern of dioxins in human breast milk in southern Vietnam.

    PubMed

    Tawara, Kenji; Nishijo, Muneko; Maruzeni, Shoko; Nakagawa, Hideaki; Kido, Teruhiko; Naganuma, Rie; Suzuki, Hiroyuki; Nhu, Dang Duc; Hung, Nguyen Ngoc; Thom, Le Thi Hong

    2011-08-01

    This study evaluated residual congener patterns of dioxin/furan (=PCDD/DF) related to tactical herbicides aerially sprayed over the regions of southern Vietnam through Operation Ranch Hand. The study focused on Cam Chinh (CC) commune, Quang Tri province (an area sprayed with tactical herbicides), and the Cam Phuc (CP) commune, Ha Tinh province (a non-sprayed area). Breast milk samples for analysis were collected in September 2002 and July 2003 from lactating primiparous and multiparous mothers born after the war (<31 years old). We found the levels of each congener in the CC commune were higher than in the CP commune, and determined specificity in the PCDD/DF congener pattern in CC commune samples by cluster analysis. The congener pattern is characterized by higher (the hexa-, the hepta-, and the octa-) chlorinated PCDD/DFs; this appears to be the same profile as that presented by pentachlorophenol (PCP), rather than 2,4,5-trichlorophenoxy acid (2,4,5-T) contaminated with 2,3,7,8-TCDD. A GC/MS study in the 1970s detected the chlorophenols 2,4-di and 2,4,6-trichlorophenol in some Agent Orange samples, which contained, like PCP, a wide variety of PCDD/DF congeners. In this context, it may be expected that certain tactical herbicides contaminated with various chlorophenol impurities, have a unique congener pattern when compared with pure 2,4,5-T formulations. PMID:21680010

  1. Trait responses of invasive aquatic macrophyte congeners: colonizing diploid outperforms polyploid

    PubMed Central

    Grewell, Brenda J.; Skaer Thomason, Meghan J.; Futrell, Caryn J.; Iannucci, Maria; Drenovsky, Rebecca E.

    2016-01-01

    Understanding traits underlying colonization and niche breadth of invasive plants is key to developing sustainable management solutions to curtail invasions at the establishment phase, when efforts are often most effective. The aim of this study was to evaluate how two invasive congeners differing in ploidy respond to high and lowresource availability following establishment from asexual fragments. Because polyploids are expected to have wider niche breadths than diploid ancestors, we predicted that a decaploid species would have superior ability to maximize resource uptake and use, and outperform a diploid congener when colonizing environments with contrasting light and nutrient availability. A mesocosm experiment was designed to test the main and interactive effects of ploidy (diploid and decaploid) and soil nutrient availability (low and high) nested within light environments (shade and sun) of two invasive aquatic plant congeners. Counter to our predictions, the diploid congener outperformed the decaploid in the early stage of growth. Although growth was similar and low in the cytotypes at low nutrient availability, the diploid species had much higher growth rate and biomass accumulation than the polyploid with nutrient enrichment, irrespective of light environment. Our results also revealed extreme differences in time to anthesis between the cytotypes. The rapid growth and earlier flowering of the diploid congener relative to the decaploid congener represent alternate strategies for establishment and success. PMID:26921139

  2. Net trophic transfer efficiencies of polychlorinated biphenyl congeners to lake whitefish (Coregonus clupeaformis) from their food

    USGS Publications Warehouse

    Madenjian, C.P.; O'Connor, D.V.; Rediske, R.R.; O'Keefe, J. P.; Pothoven, S.A.

    2008-01-01

    Lake whitefish (Coregonus clupeaformis) were fed rainbow smelt (Osmerus mordax) in four laboratory tanks over a 133-d experiment. At the start of the experiment, 10 to 14 of the fish in each tank were sacrificed, and the concentrations of 40 polychlorinated biphenyl (PCB) congeners within these fish were determined. Polychlorinated biphenyl congener concentrations were also determined in the 15 lake whitefish remaining in each of the four tanks at the end of the experiment as well as in the rainbow smelt fed to the lake whitefish. Each lake whitefish was weighed at the start and the end of the experiment, and the amount of food eaten by the lake whitefish during the experiment was tracked. Using these measurements, net trophic transfer efficiency (??) from the rainbow smelt to the lake whitefish in each of the four tanks was calculated for each of the 40 PCB congeners. Results showed that ?? decreased exponentially as log KOW for the congeners increased from 6 to 8. Further, ?? averaged 0.70 for the tetrachloro congeners but averaged only 0.45 for the higher chlorinated congeners. ?? 2008 SETAC.

  3. Prostaglandins and estradiol-induced attenuation of hypoxic pulmonary vasoconstriction.

    PubMed

    Sylvester, J T; Gordon, J B; Malamet, R L; Wetzel, R C

    1985-10-01

    Pretreatment with estradiol (20 mg IM) attenuated vasoreactivity to decreases in inspired PIO2, lowered baseline resistance measured under conditions of maximal vasodilation (PIO2 = 0 mm Hg), and appeared to increase prostaglandin release in isolated, blood-perfused lungs of juvenile female sheep. Indomethacin (40 micrograms/ml) inhibited prostaglandin release and restored hypoxic vasoreactivity in estrogen-treated lungs, but did not alter the estrogen-induced decrease in baseline resistance. These results suggest that estradiol enhanced the production of prostaglandins which secondarily attenuated hypoxic vasoreactivity. The estradiol-induced decrease in baseline resistance, however, must have been mediated by some other mechanism.

  4. 3D model of amphioxus steroid receptor complexed with estradiol

    SciTech Connect

    Baker, Michael E.; Chang, David J.

    2009-08-28

    The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen-binding to steroid receptors, we constructed a 3D model of amphioxus SR complexed with estradiol. This 3D model indicates that although the SR is activated by estradiol, some interactions between estradiol and human ER{alpha} are not conserved in the SR, which can explain the low affinity of estradiol for the SR. These differences between the SR and ER{alpha} in the steroid-binding domain are sufficient to suggest that another steroid is the physiological regulator of the SR. The 3D model predicts that mutation of Glu-346 to Gln will increase the affinity of testosterone for amphioxus SR and elucidate the evolution of steroid-binding to nuclear receptors.

  5. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  6. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  7. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  8. GENERATING THE RIGHT PCB DATA DETERMINATION OF AROCLORS VERSUS PCB CONGENERS

    SciTech Connect

    NARQUIS CT; PRIGNANO AL

    2007-11-21

    Polychlorinated biphenyls (PCBs) are a major environmental concern due to their ubiquity and tendency to bio-accumulate. as well as their persistence and toxicity. As the cleanup of waste and contaminated soil progresses at U.S. Department of Energy (DOE) sites, the costs for accurate PCB data are increasing. PCBs are actually a broad name for a group of 209 individual compounds known as congeners. PCBs were originally produced in the United States as specific mixtures of congeners known as Aroclors'. PCBs can be analyzed and quantified either as Aroclor mixtures or as individual congeners. Aroclor analysis, which is the more common analytical method applied to PCBs. has been in use for decades, and in general, most cleanup regulations are based on total PCB concentrations using Aroclor analyses. Congener analysis is relatively new to environmental cleanup and restoration due to both technical issues and associated cost. The benefits of congener analysis are that it allows a more direct analysis of the risk of the PCBs. The World Health Organization (WHO) has identified twelve specific congeners as dioxin-like with toxicity ranging from 0.00003 to 0.1 times the standard 2,3,7.8-Tetrachlorodibenzo-p-dioxin (2.3.7.8-TCDD) toxicity. This paper defines Aroclors and congeners and compares the current application and usefulness of the two analytical methods for environmental restoration and cleanup. A strategy for the best use of the two methods to optimize overall characterization cost is presented. As part of the strategy. a method using the data from Aroclor analyses to calculate 2,3,7,8-TCDD toxicity equivalent concentrations is also presented.

  9. Generating the Right PCB Data: Determination of Aroclors Versus PCB Congeners

    SciTech Connect

    Prignano, A.L.; Narquis, C.T.; Hyatt, J.E.

    2008-07-01

    Polychlorinated biphenyls (PCBs) are a major environmental concern due to their ubiquity and tendency to bio-accumulate, as well as their persistence and toxicity. As the cleanup of waste and contaminated soil progresses at U.S. Department of Energy (DOE) sites, the costs for accurate PCB data are increasing. PCBs are actually a broad name for a group of 209 individual compounds known as congeners. PCBs were originally produced in the United States as specific mixtures of congeners known as Aroclors. PCBs can be analyzed and quantified either as Aroclor mixtures or as individual congeners. Aroclor analysis, which is the more common analytical method applied to PCBs, has been in use for decades, and in general, most cleanup regulations are based on total PCB concentrations using Aroclor analyses. Congener analysis is relatively new to environmental cleanup and restoration due to both technical issues and associated cost. The benefits of congener analysis are that it allows a more direct analysis of the risk of the PCBs. The World Health Organization (WHO) has identified twelve specific congeners as dioxin-like with toxicity ranging from 0.00003 to 0.1 times the standard 2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) toxicity. This paper defines Aroclors and congeners and compares the current application and usefulness of the two analytical methods for environmental restoration and cleanup. A strategy for the best use of the two methods to optimize overall characterization cost is presented. As part of the strategy, a method using the data from Aroclor analyses to calculate 2,3,7,8-TCDD toxicity equivalent concentrations is also presented. (authors)

  10. Association Between Preovulatory Concentrations of Estradiol and Expression of Uterine Milk Protein Precursor, Inhibin Beta A, Period 1, Proenkephalin, and Receptors for Oxytocin, Progesterone, and Estradiol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eliminating the preovulatory surge of estradiol decreased uterine weight, uterine protein, RNA to DNA ratio, rate of protein synthesis, and embryo survival following embryo transfer in sheep. Furthermore, cows that did not exhibit standing estrus (decreased preovulatory concentrations of estradiol) ...

  11. Stimulation of estradiol biosynthesis by tributyltin in rat hippocampal slices.

    PubMed

    Munetsuna, Eiji; Hattori, Minoru; Yamazaki, Takeshi

    2014-01-01

    Hippocampal functions are influenced by steroid hormones, such as testosterone and estradiol. It has been demonstrated that hippocampus-derived steroid hormones play important roles in neuronal protection and synapse formation. Our research groups have demonstrated that estradiol is de novo synthesized in the rat hippocampus. However, the mechanism(s) regulating this synthesis remains unclear. It has been reported that tributyltin, an environmental pollutant, binds to the retinoid X receptor (RXR) and modifies estrogen synthesis in human granulosa-like tumor cells. This compound can penetrate the blood brain barrier, and tends to accumulate in the brain. Based on these facts, we hypothesized that tributyltin could influence the hippocampal estradiol synthesis. A concentration of 0.1 μM tributyltin induced an increase in the mRNA content of P450(17α) and P450arom in hippocampal slices, as determined using real-time PCR. The transcript levels of other steroidogenic enzymes and a steroidogenic acute regulatory protein were not affected. The estradiol level in rat hippocampal slices was subsequently determined using a radioimmunoassay. We found that the estradiol synthesis was stimulated by ∼2-fold following a 48-h treatment with 0.1 μM tributyltin, and this was accompanied by transcriptional activation of P450(17α) and P450arom. Tributyltin stimulated de novo hippocampal estradiol synthesis by modifying the transcription of specific steroidogenic enzymes. PMID:24679120

  12. Estradiol signaling via sequestrable surface receptors.

    PubMed

    Benten, W P; Stephan, C; Lieberherr, M; Wunderlich, F

    2001-04-01

    Estradiol (E(2))-signaling is widely considered to be exclusively mediated through the transcription-regulating intracellular estrogen receptor (ER) alpha and ERbeta. The aim of this study was to investigate transcription-independent E(2)-signaling in mouse IC-21 macrophages. E(2) and E(2)-BSA induce a rapid rise in the intracellular free Ca(2+) concentration ([Ca(2+)](i)) of Fura-2 loaded IC-21 cells as examined by spectrofluorometry. These changes in [Ca(2+)](i) can be inhibited by pertussis toxin, but not by the ER-blockers tamoxifen and raloxifene. The E(2)-signaling initiated at the plasma membrane is mediated through neither ERalpha nor ERbeta, but rather through a novel G protein-coupled membrane E(2)-receptor as revealed by RT-PCR, flow cytometry, and confocal laser scanning microscopy. A special feature of this E(2)-receptor is its sequestration upon agonist stimulation. Sequestration depends on energy and temperature, and it proceeds through a clathrin- and caveolin-independent pathway. PMID:11250949

  13. Origin of serum estradiol in postmenopausal women.

    PubMed

    Judd, H L; Shamonki, I M; Frumar, A M; Lagasse, L D

    1982-06-01

    In postmenopausal women, the circulating levels of estrone (E1) and estradiol (E2) may be of clinical importance. The origin of E1, but not of E2, has been defined. To examine the source of the latter, the serum concentrations, metabolic clearance rates, conversion ratios, and production rates of testosterone (T), androstenedione (A), E2, and E1 were measured in 20 postmenopausal subjects. For E2, the mean +/- SE CRTE2 was 0.0014 +/- 0.0005; thus, the contribution of circulating T to the circulating E2 pool was minimal (2.5%). The contribution of circulating A to E2 was also insignificant, whereas the CRE1E2 was appreciable (0.065 +/- 0.011), accounting for 21.5% of the E2 pool. For E1, the major contribution was the peripheral conversion of A, accounting for 24.6% of circulating E1. The contribution of peripheral conversion of T (unmeasurable) and E2 (2.9%) to the E1 pool were minimal. These data are consistent with the concept that in postmenopausal women the major contribution of peripheral conversion to the circulating E2 pool is from E1, which in turn is the product of peripheral aromatization of circulating A. PMID:7078905

  14. Differential effects of two lots of aroclor 1254: congener-specific analysis and neurochemical end points.

    PubMed Central

    Kodavanti, P R; Kannan, N; Yamashita, N; Derr-Yellin, E C; Ward, T R; Burgin, D E; Tilson, H A; Birnbaum, L S

    2001-01-01

    Aroclor 1254 is a widely studied commercial polychlorinated biphenyl (PCB) mixture which, by definition, contains 54% chlorine by weight. Recent reports indicate substantial differences in the congener composition among Aroclor lots and hence their biologic effects. We designed the current study to compare the effects of two lots of Aroclor 1254 (lots 6024 and 124-191). We analyzed these two lots for PCB congeners, polychlorinated dibenzofurans (PCDFs), polychlorinated naphthalenes (PCNs), and polychlorinated dibenzodioxins (PCDDs). We used previously established techniques for analyzing intracellular Ca(2+) buffering and protein kinase C (PKC) translocation to test their biologic activity in neuronal preparations. PCB congener-specific analysis indicated that ortho and non-ortho congeners in these two lots varied in their percent contribution. Among all congeners, the percentages of non-ortho congeners (PCBs 77, 81, 126, and 169) were higher in lot 6024 (2.9% of total) than in lot 124-191 (0.02% of total). We detected no dioxins in these two lots (< 2 ppb). Although there are some differences in the congener composition, total PCNs were similar in both lots: 171 ppm in lot 6024 and 155 ppm in lot 124-191. However, total PCDFs were higher in lot 6024 (38.7 ppm) than in lot 124-191 (11.3 ppm). When we tested these two Aroclors on Ca(2+) buffering and PKC translocation in brain preparations, the effects were significantly different. Although lot 124-191 was more potent on PKC translocation than lot 6024, lot 6024 was slightly more active on Ca(2+) buffering than lot 124-191. These effects could not be attributed to the differences in the percentage of non-ortho congeners or PCDFs because they were inactive on these two parameters. The effects could not be attributed to PCNs because the levels were almost similar. The effects seen with two lots of Aroclor 1254 in neuronal cells were also not predicted based on the TCDD toxic equivalents (TEQs), although TEQs predicted

  15. Polychlorinated biphenyl (PCB) congener concentrations in seabirds found dead in mortality incidents around the British coast.

    PubMed

    Malcolm, H M; Osborn, D; Wright, J; Wienburg, C L; Sparks, T H

    2003-07-01

    Livers from 121 birds killed in mortality incidents in U.K. coastal waters between 1991 and 1996 were analyzed for 16 PCB congeners (IUPAC numbers 8, 18, 28, 31, 52, 77, 101, 118, 126, 128, 138, 149, 153, 169, 170, and 180). Species analyzed were guillemot (Uria aalge), shag (Phalacrocorax arisotelis), kittiwake (Rissa tridactyla), puffin (Fratercula arctica), razorbill (Alca torda), fulmar (Fulmarus glacialis), gannet (Sula bassana), and herring gull (Larus argentatus). This is the first report of PCBs in U.K. seabird tissues to be presented since 1983. Mean concentrations of total PCBs ranged from 0.47 to 15.8 mg/kg WW, similar to concentrations reported for North Sea birds during the 1970s and 1980s and lower than those reported for the same species in the Irish Sea during the late 1960s and early 1970s. The congeners generally present in the highest concentrations were (in decreasing order) 153, 138, 180, 118, and 170. Despite the birds having similar diets, both inter- and intraspecies differences in PCB congener profile were found. In guillemots from several sites on the east coast, the dominant congener was 138, compared to guillemots from the south coast, which had the more typical congener pattern found in seabirds. Some of the differences in total PCB values could be due to different causes of death, with a subsequent effect on body lipid levels. PMID:12948183

  16. Deconvolution of Soft Ionization Mass Spectra of Chlorinated Paraffins To Resolve Congener Groups.

    PubMed

    Yuan, Bo; Alsberg, Tomas; Bogdal, Christian; MacLeod, Matthew; Berger, Urs; Gao, Wei; Wang, Yawei; de Wit, Cynthia A

    2016-09-20

    We describe and illustrate a three-step data-processing approach that enables individual congener groups of chlorinated paraffins (CPs) to be resolved in mass spectra obtained from either of two soft ionization methods: electron capture negative ionization mass spectrometry (ECNI-MS) or atmospheric pressure chemical ionization mass spectrometry (APCI-MS). In the first step, general fragmentation pathways of CPs are deduced from analysis of mass spectra of individual CP congeners. In the second step, all possible fragment ions in the general fragmentation pathways of CPs with 10 to 20 carbon atoms are enumerated and compared to mass spectra of CP mixture standards, and a deconvolution algorithm is applied to identify fragment ions that are actually observed. In the third step, isotope permutations of the observed fragment ions are calculated and used to identify isobaric overlaps, so that mass intensities of individual CP congener groups can be deconvolved from the unresolved isobaric ion signal intensities in mass spectra. For a specific instrument, the three steps only need to be done once to enable deconvolution of CPs in unknown samples. This approach enables congener group-level resolution of CP mixtures in environmental samples, and it opens up the possibility for quantification of congener groups. PMID:27531279

  17. Organic Anion Transporting Polypeptides in the Hepatic Uptake of PBDE Congeners in Mice

    PubMed Central

    Pacyniak, Erik; Hagenbuch, Bruno; Klaassen, Curtis D.; McKeeman, Lois Lehman; Guo, Grace L.

    2011-01-01

    BDE47, BDE99 and BDE153 are the predominant polybrominated diphenyl ether (PBDE) congeners detected in humans and can induce drug metabolizing enzymes in the liver. We have previously demonstrated that several human liver organic anion transporting polypeptides (humans: OATPs; rodents: Oatps) can transport PBDE congeners. Mice are commonly used to study the toxicity of chemicals like the PBDE congeners. However, the mechanism of the hepatic PBDE uptake in mice is not known. Therefore, the purpose of the current study was to test the hypothesis that BDE47, BDE99, and BDE153 are substrates of mouse hepatic Oatps (Oatp1a1, Oatp1a4, Oatp1b2, and Oatp2b1). We used Human Embryonic Kidney 293 (HEK293) cells transiently expressing individual Oatps and quantified the uptake of BDE47, BDE99, and BDE153. Oatp1a4, Oatp1b2, and Oatp2b1 transported all three PBDE congeners, whereas Oatp1a1 did transport none. Kinetic studies demonstrated that Oatp1a4 and Oatp1b2 transported BDE47 with the greatest affinity, followed by BDE99 and BDE153. In contrast, Oatp2b1 transported all three PBDE congeners with similar affinities. The importance of hepatic Oatps for the liver accumulation of BDE47 was confirmed using Oatp1a4-, and Oatp1b2-null mice. PMID:21884716

  18. Net trophic transfer efficiencies of polychlorinated biphenyl congeners to lake trout (Salvelinus namaycush) from its prey

    USGS Publications Warehouse

    Madenjian, Charles P.; David, Solomon R.; Rediske, Richard R.; O’Keefe, James P.

    2012-01-01

    Lake trout (Salvelinus namaycush) were fed bloater (Coregonus hoyi) in eight laboratory tanks over a 135-d experiment. At the start of the experiment, four to nine fish in each tank were sacrificed, and the concentrations of 75 polychlorinated biphenyl (PCB) congeners within these fish were determined. Polychlorinated biphenyl congener concentrations were also determined in the 10 lake trout remaining in each of the eight tanks at the end of the experiment as well as in the bloater fed to the lake trout. Each lake trout was weighed at the start and the end of the experiment, and the amount of food eaten by the lake trout was recorded. Using these measurements, net trophic transfer efficiency (γ) from the bloater to the lake trout in each of the eight tanks was calculated for each of the 75 congeners. Results showed that γ did not vary significantly with the degree of chlorination of the PCB congeners, and γ averaged 0.66 across all congeners. However,γ did show a slight, but significant, decrease as logKOW increased from 6.0 to 8.2. Activity level of the lake trout did not have a significant effect on γ.

  19. Evaluating Estradiol Levels in Male Patients with Colorectal Carcinoma

    PubMed Central

    Seth, Shashi; Arora, Kanchan; Verma, Monica

    2015-01-01

    Background: Globally more than 1 million people suffer from colorectal cancer (CRC) per annum, resulting in about 0.5 million deaths. The role of estrogen in CRC is being researched with great interest; expression of estrogen receptors (alfa and beta) is being explored. Aims and Objective: Our objective was to compare the serum estradiol levels in diagnosed male patients of CRC, with age-matched controls; and to study the estradiol levels across the different stages of CRC. Setting and design: A cross-sectional study was conducted from January, 2012 to March, 2013 at a tertiary care hospital in north India. Materials and Methods: Fifty one male preoperative CRC patients were enrolled along with 50 age-matched male controls. Ethical approval and informed written consent from each participant were duly obtained. CRC patients were staged as per TNM (T- Tumour, N- Node, M- Metastasis; I, II, III and IV) criteria. Serum estradiol level was measured by Chemiimmunofluroscence method (normal = 11.6 - 41.2 pg/ml). Statistical analysis used: We used student’s t test and ANOVA (analysis of variance) to analyse the data (SPSS version 17.0, SPSS, Inc., Chicago, Illinois) Result: The mean serum estradiol level among CRC patients (43.4, sd=27.1) was significantly more than that among controls (mean=24.7, sd=17.5), (p<0.0001). Across the four TNM stages of CRC patients, mean estradiol level was highest in Stage II (55.9, sd=15.5); followed by Stages III (44.1, sd=24.9), IV (36.3, sd=30.0) and I (26.4, sd=38.8). However, significant difference was obtained only between Stages I and II. Conclusion: Our study revealed increased levels of serum estradiol in Indian male CRC patients. Further research is warranted to corroborate this finding, and to understand the role of estradiol across different TNM stages of CRC. PMID:25737973

  20. Enhanced osteoblast proliferation and collagen gene expression by estradiol

    SciTech Connect

    Ernest, M.; Schmid, Ch.; Froesch, E.R. )

    1988-04-01

    Estrogens play a crucial role in the development of postmenopausal osteoporosis. However, the mechanism by which estrogens exert their effects on bone is unknown. To examine possible direct effects of 17{beta}-estradiol on bone-forming cells, the authors used pure rat osteoblast-like cells in vitro as a model. Osteoblast-like cells prepared from calvaria of newborn rats were cultured serum-free in methylcellulose-containing medium for 21 days. Osteoblast-like cells proliferate selectively into clonally derived cell clusters of spherical morphorlogy. 17{beta}-Estradiol at concentrations of 0.1 nM and 1 nM enhanced osteoblast-like cell proliferation by 41% and 68% above vehicle-treated controls. The biologically inactive stereoisomer 17{alpha}-estradiol (same concentrations) had no effect. Moreover, the antiestrogen tamoxifen abolished the stimulation of osteoblast-like cell proliferation by 17{beta}-estradiol. After 21 days of culture, RNA was prepared and analyzed in a dot-hybridization assay for the abundance of pro{alpha}1(I) collagen mRNA. Steady-state mRNA levels were increased in cultures treated with 17{beta}-estradiol in a dose-dependent manner with maximal stimulation at 1 nM and 10 nM. At the same concentrations, the percentage of synthesized protein (labeled by ({sup 3}H)proline pulse) that was digestible by collagenase was increased, indicating that 17{beta}-estradiol acts as pretranslational levels to enhance synthesis of bone collagen. These data show that the osteoblast is a direct target for 17{beta}-estradiol.

  1. Subchronic effects of five di-ortho PCB congeners on survival, growth and reproduction in the fathead minnow Pimephales promelas

    SciTech Connect

    Suedel, B.C.; Dillon, T.M.; Benson, W.H.

    1997-07-01

    The effects of five di-ortho polychlorinated biphenyl (PCB) congeners on survival, growth, and reproduction in the fathead minnow. Pimephales promelas, were determined. Fish were exposed to one of two nominal concentrations of each congener for a total of 13 weeks (7-week prespawning period plus 6-week spawning period) under flow-through conditions using methanol as a carrier solvent. At termination, P. promelas survival was high in all PCB congener treatments. PCB congeners had no significant sublethal effects on reproductive success within the concentration range examined. The total number of eggs, clutch size, number of clutches, percent hatchability, and presence of terata in offspring were not significantly affected. Reproductive success was slightly but not significantly enhanced in the solvent control and high treatment concentrations for congeners 52, 101, 138, and 153. Growth expressed as wet weight was not affected for both adult males or females. Male lengths were not significantly affected but female lengths were significantly reduced when exposed to congeners 101, 138, 153, and 180. Pimephales promelas accumulated substantial amounts of all PCBs, with tissue concentrations ranging from 13 to 183 mg/kg wet weight at termination in PCB-exposed fish. These tissue residues are one to several orders of magnitude greater than those reported for these congeners in aquatic biota previously collected in industrial waterways of the Great Lakes. Several di-ortho PCB congeners frequently found in aquatic biota showed minimal adverse effects on fathead minnow survival, growth, and reproduction even though bioaccumulation of these congeners was substantial.

  2. Direct measurement of octanol-water partition coefficients of some environmentally relevant brominated diphenyl ether congeners.

    PubMed

    Braekevelt, Eric; Tittlemier, Sheryl A; Tomy, Gregg T

    2003-05-01

    Octanol-water partition coefficients (K(OW)) of nine environmentally relevant brominated diphenyl ether (BDE) congeners present in two technical mixtures were directly measured using a slow-stir technique. LogK(OW) values of tri- to heptabrominated BDE congeners ranged from 5.74 to 8.27, and were related to bromine content by the equation logK(OW)=0.621(#Br)+4.12(R(2)=0.970). The directly determined K(OW) values were generally lower than those calculated using fragment constant methods, particularly at higher levels of bromine substitution. The quasi-experimental approach of using fragment constants to modify a "backbone" compound of known K(OW) was much more successful than using the fragment constants to "build" the entire molecule. The tri- and tetrabrominated congeners are in the range of optimum bioaccumulation potential. PMID:12615110

  3. [Change in congener analysis caused by percutaneous absorption of propanol-containing antiseptics].

    PubMed

    Peschel, O; Bauer, M F; Gilg, T; Meyer, L V; von Meyer, L

    1992-05-01

    According to the forensic literature, an alteration of blood alcohol concentration through alcohol disinfection before venepuncture is unlikely, however, percutaneous resorption of alcohol containing antiseptics is well documented. There are no investigations available, elucidating to what extent this is also correct for congener alcohols, particularly propanol-1/-2, which have serum levels in range of mg/l. In experiments with surgical hand and local skin disinfection, carried out with and without oral alcohol, relevant levels of propanol-1/-2 between 0.2 and 2 mg/l were measured. We conclude, that the routine clinical use of antiseptics is able to alterate and to falsify congener levels and can lead to incorrect interpretation of congener analysis.

  4. Polychlorinated biphenyl congeners in emergent mayflies from the upper Mississippi River

    USGS Publications Warehouse

    Steingraeber, M.T.; Schwartz, T.R.; Wiener, J.G.; Lebo, J.A.

    1994-01-01

    We determined polychlorinated biphenyls (pcbs) in emergent mayflies (hexagenia bilineata) from a 1250-km reach of the upper mississippi river (umr). Total pcb concentrations (sum of 125 congeners) ranged from 0.21 To 4.1 Mu g/g of dry weight (1.2-29 mu g/g of lipid weight). Concentrations were highest in pools near the twin cities and the quad cities metropolitan areas. Longitudinal movement of pcbs was extensive downstream from the twin cities (175-320 km) but was not apparent downstream from the quad cities. The pcb composition of mayflies was relatively homogeneous throughout most of the river. However, the congener composition in mayflies from two distant locations differed markedly from the other samples and contained a greater abundance of lower molecular weight congeners. Recent pcb discharges from point and nonpoint sources may account for these differences. Emergent mayflies seem to be a useful indicator of pcb contamination of the umr.

  5. Detailed PCB congener characterization of influent and effluent at New York and New Jersey WPCPs

    SciTech Connect

    Durell, G.S.; Lizotte, R.D. Jr.; Solomon, M.H.; Green, J.W.; Spadone, J.; Pires, L.

    1995-12-31

    The waste streams at 26 New York City and New Jersey water pollution control plants (WPCP) were characterized for PCB. Time-integrated influent and effluent samples were collected during normal and high (storm) flow conditions; high flow influent simulated what may by-pass the plant and be discharged through combined sewer overflows. State-of-the-art congener-specific analytical methods were used to achieve detection limits from 0.05 to 0.3 ng/L. Concentrations of 71 individual PCB congeners that constitute approximately 95% of the total PCB in Aroclors and environmental samples were determined. The PCB concentrations and congener distributions varied notably among plants. Individual congener concentrations were typically well below 1 ng/L in the effluent, with a few congeners being detected at 5 to 10 ng/L levels in some samples. The concentrations were under 1 ng/L in most influent samples, with occasional determinations above 10 ng/L. The average total PCB concentration, defined as the sum of the 71 individual congener concentrations, at the 26 WPCPs were 27, 110, and 160 ng/L for normal flow effluent, normal flow influent, and high flow influent, respectively. The results indicate that PCB levels in New York City and New Jersey WPCP discharges are generally low, with most effluent having total PCB concentrations below 0.05 {micro}g/L. The PCB levels in the influent were commonly under 0.1 {micro}g/L and became slightly elevated at most plants during storms while at some plants the increase in flow appeared to dilute the PCB in the influent. The WPCPs remove, on average, approximately 75% of the PCB received in the influent.

  6. The role of estradiol in male reproductive function

    PubMed Central

    Schulster, Michael; Bernie, Aaron M; Ramasamy, Ranjith

    2016-01-01

    Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido. PMID:26908066

  7. Estradiol selectively enhances auditory function in avian forebrain neurons.

    PubMed

    Caras, Melissa L; O'Brien, Matthew; Brenowitz, Eliot A; Rubel, Edwin W

    2012-12-01

    Sex steroids modulate vertebrate sensory processing, but the impact of circulating hormone levels on forebrain function remains unclear. We tested the hypothesis that circulating sex steroids modulate single-unit responses in the avian telencephalic auditory nucleus, field L. We mimicked breeding or nonbreeding conditions by manipulating plasma 17β-estradiol levels in wild-caught female Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii). Extracellular responses of single neurons to tones and conspecific songs presented over a range of intensities revealed that estradiol selectively enhanced auditory function in cells that exhibited monotonic rate level functions to pure tones. In these cells, estradiol treatment increased spontaneous and maximum evoked firing rates, increased pure tone response strengths and sensitivity, and expanded the range of intensities over which conspecific song stimuli elicited significant responses. Estradiol did not significantly alter the sensitivity or dynamic ranges of cells that exhibited non-monotonic rate level functions. Notably, there was a robust correlation between plasma estradiol concentrations in individual birds and physiological response properties in monotonic, but not non-monotonic neurons. These findings demonstrate that functionally distinct classes of anatomically overlapping forebrain neurons are differentially regulated by sex steroid hormones in a dose-dependent manner.

  8. The role of estradiol in male reproductive function.

    PubMed

    Schulster, Michael; Bernie, Aaron M; Ramasamy, Ranjith

    2016-01-01

    Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido. PMID:26908066

  9. Estradiol binding to nuclear matrix protein of pig adrenal cortex

    SciTech Connect

    Ungar, F.; Johnson, S.R.; Johnston, J.A.

    1987-05-01

    Binding of TH-estradiol can be shown in vitro after incubation with purified washed nuclei of sow adrenal cortex or with the insoluble nuclear matrix protein isolated from nuclei. The procedure modified after Berezney and Coffey treated washed nuclei sequentially with 1% Triton-X100, DNase, RNase and 2M NaCl to give an insoluble nuclear matrix protein preparation in which most of the phospholipid, DNA, RNA and protein was removed. Reagents were added to 10 mM Tris buffer containing 1 mM phenylmethyl sulfonyl fluoride, dithiothreitol and 0.2 mM or 5.0 mM MgCl2. Each treatment and washes were centrifuged at 4C. Suspensions of nuclei and nuclear matrix protein were incubated at 4C for 24 hrs. with 0.25 to 3.0 ng of TH-estradiol in 0.5 ml 10 mM Tris buffer with 5 mM MgCl2. Scatchard analysis of binding in duplicate or triplicate tubes with or without excess unlabeled estradiol gave specific binding for sow adrenal nuclei and for nuclear matrix protein. Total binding sites varied between 780 to 1380 fmoles/mg protein. Estradiol binding was not shown in the fetal adrenal matrix nor in mitochondria. Noncompetitive controls included progesterone and pregnenolone. Nuclear matrix protein binding of estradiol may have significance in functional or morphological changes of the adrenal cortex in fetal, neonatal, or pubertal development.

  10. β-Estradiol and ethinyl-estradiol contamination in the rivers of the Carpathian Basin.

    PubMed

    Avar, Péter; Zrínyi, Zita; Maász, Gábor; Takátsy, Anikó; Lovas, Sándor; G-Tóth, László; Pirger, Zsolt

    2016-06-01

    17β-Estradiol (E2) and 17α-ethinyl estradiol (EE2), which are environmental estrogens, have been determined with LC-MS in freshwater. Their sensitive analysis needs derivatization and therefore is very hard to achieve in multiresidue screening. We analyzed samples from all the large and some small rivers (River Danube, Drava, Mur, Sava, Tisza, and Zala) of the Carpathian Basin and from Lake Balaton. Freshwater was extracted on solid phase and derivatized using dansyl chloride. Separation was performed on a Kinetex XB-C18 column. Detection was achieved with a benchtop orbitrap mass spectrometer using targeted MS analysis for quantification. Limits of quantification were 0.05 ng/L (MS1) and 0.1 ng/L (MS/MS) for E2, and 0.001 ng/L (MS1) and 0.2 ng/L (MS/MS) for EE2. River samples contained n.d.-5.2 ng/L E2 and n.d.-0.68 ng/L EE2. Average levels of E2 and EE2 were 0.61 and 0.084 ng/L, respectively, in rivers, water courses, and Lake Balaton together, but not counting city canal water. EE2 was less abundant, but it was still present in almost all of the samples. In beach water samples from Lake Balaton, we measured 0.076-0.233 E2 and n.d.-0.133 EE2. A relative high amount of EE2 was found in river Zala (0.68 ng/L) and in Hévíz-Páhoki canal (0.52 ng/L), which are both in the catchment area of Lake Balaton (Hungary).

  11. Sympathetic regulation of estradiol secretion from the ovary.

    PubMed

    Uchida, Sae

    2015-01-01

    It is well known that hormone secretion from endocrine glands is regulated by hierarchical feedback mechanisms. However, although Cannon revealed in the 1920s that sympathoadrenal medullary function increased during emergency situations, no studies on the autonomic nervous regulation of hormone secretion have been undertaken for many years. In the past 40 years, the autonomic nervous regulation of insulin secretion from the pancreas, gastrin secretion from the stomach, glucocorticoid secretion from the adrenal cortex, etc., has been demonstrated. Estradiol secretion from the ovary is strongly controlled by the hypothalamic-pituitary-ovarian axis, and its possible regulation by autonomic nerves has been largely unnoticed. Some histological studies have revealed rich adrenergic sympathetic innervation in the ovary. Recently, it has been demonstrated that the activation of the sympathetic nerves to the ovary directly reduces estradiol secretion from the ovary. This article reviews physiological and morphological studies, primarily in rats, on the sympathetic regulation of estradiol secretion from the ovary.

  12. Testosterone, estradiol, ACTH and musical, spatial and verbal performance.

    PubMed

    Hassler, M; Gupta, D; Wollmann, H

    1992-01-01

    Testosterone, estradiol, and ACTH were determined in blood serum of 26 healthy males aged 19.16 and of 25 healthy females aged 18.77 years on average, and results were correlated with test scores of three spatial tests, a verbal fluency measure, and a test measuring general musical ability. In addition, hemispheric lateralization for verbal material and handedness was assessed. While testosterone and estradiol alone were not significantly related to any of the cognitive or musical tests, testosterone/estradiol ratio was significantly negatively correlated with spatial tests, and ACTH was significantly positively correlated with spatial and musical tests. Correlations were stronger in females than in males. The laterality index was significantly negatively correlated with testosterone in males indicating that right hemisphere involvement in verbal processing was associated with high testosterone levels.

  13. Membrane-initiated estradiol actions mediate structural plasticity and reproduction

    PubMed Central

    Micevych, Paul; Christensen, Amy

    2012-01-01

    Over the years, our ideas about estrogen signaling have greatly expanded. In addition to estradiol having direct nuclear actions that mediate transcription and translation, more recent experiments have demonstrated membrane-initiated signaling. Both direct nuclear and estradiol membrane signaling can be mediated by the classical estrogen receptors, ERα and ERβ, which are two of the numerous putative membrane estrogen receptors. Thus far, however, only ERα has been shown to play a prominent role in regulating female reproduction and sexual behavior. Because ERα is a ligand-gated transcription factor and not a typical membrane receptor, trafficking to the cell membrane requires post-translational modifications. Two necessary modifications are palmitoylation and association with caveolins, a family of scaffolding proteins. In addition to their role in trafficking, caveolin proteins also serve to determine ERα interactions with metabotropic glutamate receptors (mGluRs). It is through these complexes that ERα, which cannot by itself activate G proteins, is able to initiate intracellular signaling. Various combinations of ERα-mGluR interactions have been demonstrated throughout the nervous system from hippocampus to striatum to hypothalamus to dorsal root ganglion (DRG) in both neurons and astrocytes. These combinations of ER and mGluR allow estradiol to have both facilitative and inhibitory actions in neurons. In hypothalamic astrocytes, the estradiol-mediated release of intracellular calcium stores regulating neurosteroid synthesis requires ERα-mGluR1a interaction. In terms of estradiol regulation of female sexual receptivity, activation of ERα-mGluR1a signaling complex leads to the release of neurotransmitters and alteration of neuronal morphology. This review will examine estradiol membrane signaling (EMS) activating a limbic-hypothalamic lordosis regulating circuit, which involves ERα trafficking, internalization, and modifications of neuronal morphology

  14. ANALYSIS OF CHIRAL PESTICIDES AND POLYCHLORINATED BIPHENYL CONGENERS IN ENVIRONMENTAL SAMPLES

    EPA Science Inventory

    Over 25 % of pesticides and other toxic organic pollutants are chiral, as are 19 of the 209 polychlorinated biphenyl (PCB) congeners; that is, they exist as two mirror image species called enantiomers (PCB enantiomers are called atropisomers). The enantiomers of a chiral compound...

  15. CONGENER-SPECIFIC DETECTION OF DIOXINS USING JET-REMPI. (R827927)

    EPA Science Inventory

    Although 210 chemically different polychlorinated dibenzo-p-dioxin and dibenzofuran congeners can be produced during combustion, it is currently believed that fewer than 20 are toxic enough to warrant monitoring. SRI is developing a continuous emissions monitor to study...

  16. MODELLING OF POLYCHLORINATED-DIOXIN AND -FURAN CONGENER PROFILES FROM MUNICIPAL WASTE COMBUSTION

    EPA Science Inventory

    The paper discusses a model, based on experimental data, that was developed to describe the profile of polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) congeners formed in the duct region of a pilot-scale combustor simulating large-scale municipal w...

  17. Elevated PCDD/F levels and distinctive PCDD/F congener profiles in free range eggs.

    PubMed

    Hsu, Jing-Fang; Chen, Chun; Liao, Pao-Chi

    2010-07-14

    Chicken eggs are one of the most important foods in the human diet all over the world, and the demand for eggs from free range hens has steadily increased. Congener-specific analyses of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were performed on 6 free range and 12 caged chicken egg samples collected in Taiwan. The mean level of PCDD/Fs in the free range egg samples was 5.7 (1.79/0.314) times higher than those in the caged egg samples. Principle component analysis revealed that at least three characteristic patterns of PCDD/F congener were observed among the 18 egg samples. The different PCDD/F congener patterns between free range and caged egg samples may reflect distinctive exposure scenarios among the free range and caged hens. We suggest that the differences of PCDD/F levels and congener patterns between free range and caged egg samples give rise to the issues related to the safety of eating free range chicken eggs. The present data may provide useful information for further investigation of the possible PCDD/F sources in the contaminated free range eggs.

  18. DIFFERENTIAL EFFECTS OF TWO LOTS OF AROCLOR 1254R: CONGENER ANALYSIS AND NEUROCHEMICAL ENDPOINTS.

    EPA Science Inventory

    Introduction
    Polychlorinated biphenyls (PCBs) are widely used in industry as heat transfer and dielectric fluids for transformers and capacitors1. PCBs were commercially produced as AroclorR mixtures in USA by the chlorination of biphenyl. Although all 209 congeners can be syn...

  19. Trait responses of invasive aquatic macrophyte congeners: colonizing diploid outperforms polyploid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding traits underlying colonization and niche breadth of invasive plants is key to developing sustainable management solutions to curtail invasions at the establishment phase, when efforts are often most effective. The aim of this study was to evaluate how two invasive congeners differing i...

  20. Congener-specific polychlorinated biphenyl patterns in eggs of aquatic birds from the Lower Laguna Madre, Texas

    SciTech Connect

    Mora, M.A.

    1996-06-01

    Eggs from four aquatic bird species nesting in the Lower Laguna Madre, Texas, were collected to determine differences and similarities in the accumulation of congener-specific polychlorinated biphenyls (PCBs) and to evaluate PCB impacts on reproduction. Because of the different toxicities of PCB congeners, it is important to know which congeners contribute most to total PCBs. The predominant PCB congeners were 153, 138, 180, 110, 118, 187, and 92. Collectively, congeners 153, 138, and 180 accounted for 26 to 42% of total PCBs. Congener 153 was the most abundant in Caspian terns (Sterna caspia) and great blue herons (Ardea herodias) and congener 138 was the most abundant in snowy egrets (Egretta thula) and tricolored herons (Egretta tricolor). Principal component analysis indicated a predominance of higher chlorinated biphenyls in Caspian terns and great blue herons and lower chlorinated biphenyls in tricolored herons. Snowy egrets had a predominance of pentachlorobiphenyls. These results suggest that there are differences in PCB congener patterns in closely related species and that these differences are more likely associated with the species` diet rather than metabolism. Total PCBs were significantly greater (p < 0.05) in Caspian terns than in the other species. Overall, PCBs in eggs of birds from the Lower Laguna Madre were below concentrations known to affect bird reproduction.

  1. Levels of specific polychlorinated biphenyl congeners in fatty foods from five Canadian cities between 1986 and 1988.

    PubMed

    Mes, J; Newsome, W H; Conacher, H B

    1991-01-01

    A total of 155 fatty food composites from five major Canadian cities were analysed for 36 selected polychlorinated biphenyl (PCB) congeners. Total PCB congener levels of more than 1 ng/g (wet weight) were found in fresh water fish, canned fish, butter, marine fish and cheese, with fresh water fish (18.7 ng/g) containing 5 to 10 times more total PCBs than the other four food commodities. Milk (2%), cooking oils/salads and canned meat soup contained less than 0.1 ng/g (wet weight). The observed total PCB residue levels in fatty foods were well within the Canadian guidelines for fish, dairy products, poultry, eggs and beef. The most predominant congeners found in fish, butter, cheese, meat and poultry were the 2,2',4,4',5-, 2,3',4,4', 5-pentachloro-, 2,2',3,4,4',5'-, 2,2',4,4',5,5'-hexachloro- and 2,2',3,4,4',5,5'-heptachlorobiphenyls. The predominant congener pattern was not always evident in other dairy products (e.g. ice cream) and processed foods (e.g. canned meat soup). An attempt was made to relate the intake of PCB congeners from fatty foods with congener levels found in adipose tissue of Canadians. The estimated daily intake of some specific PCB congeners from fatty foods, in most cases accounted for more than half the total deposit of these congeners in adipose tissue of Canadians.

  2. Estradiol and osmolality: Behavioral responses and central pathways.

    PubMed

    Curtis, Kathleen S

    2015-12-01

    Regulation of appropriate osmolality of body fluid is critical for survival, yet there are sex differences in compensatory responses to osmotic challenges. Few studies have focused on the role of sex hormones such as estradiol in behavioral responses to increases or decreases in systemic osmolality, and even fewer studies have investigated whether central actions of estrogens contribute to these responses. This overview integrates findings from a series of ongoing and completed experiments conducted in my laboratory to assess estradiol effects on water and NaCl intake in response to osmotic challenges, and on activity in central pathways that mediate such responses.

  3. Congener specificity in the accumulation of dioxins and dioxin-like compounds in zucchini plants grown hydroponically.

    PubMed

    Inui, Hideyuki; Wakai, Taketo; Gion, Keiko; Yamazaki, Kiyoshi; Kim, Yun-Seok; Eun, Heesoo

    2011-01-01

    Zucchini cultivars Cucurbita pepo subsp. ovifera cv. Patty Green and subsp. pepo cv. Gold Rush were cultivated hydroponically in a nutrient solution supplemented with a mixture of dioxins and dioxin-like compounds. Patty Green and Gold Rush showed low and high accumulation of these compounds in the aerial parts respectively. In both cultivars, the accumulation of each congener negatively depended on its hydrophobicity. This suggests that desorption and solubilization were partly responsible for congener specificity of accumulation, since this was not found in soil experiments. In contrast, no clear difference in accumulation in the roots was observed between the cultivars, whereas the translocation factors, which are indicators of efficient translocation from the roots to the aerial parts, differed among the congeners hydrophobicity-dependently. There were positive correlations between accumulation in the roots and the hydrophobicity of the polychlorinated biphenyl congeners in both cultivars. These results indicate that translocation was also partly responsible for the congener specificity and accumulation concentrations.

  4. Comparison of PBDE congeners as inducers of oxidative stress in zebrafish.

    PubMed

    Usenko, Crystal Y; Abel, Erika L; Kudela, Molly; Janise, Annie; Bruce, Erica D

    2015-05-01

    A proposed primary pathway through which polybrominated diphenyl ethers (PBDEs) disrupt normal biological functions is oxidative stress. In the present study, 4 PBDE congeners were evaluated for their potential to initiate oxidative stress in zebrafish during development: BDE 28, BDE 47, BDE 99, and BDE 100. N-acetylcysteine (NAC) was used to increase intracellular glutathione concentrations and only decreased the effects of BDE 28 at 10 ppm and 20 ppm and BDE 47 at 20 ppm. N-acetylcysteine coexposure did not alter the rates of mortality or curved body axis compared with PBDE exposure alone. The activity of glutathione-S-transferase (GST) was not altered at 24 h postfertilization (hpf), but increased following 10 ppm BDE 28 exposure at 120 hpf. Transcription of several genes associated with stress was also evaluated. At 24 hpf, cytochrome c oxidase subunit 6a (COX6a) transcription was up-regulated in embryos exposed to BDE 99, and BDE 28 exposure up-regulated the transcription of Glutathione-S-transferase-pi (GSTpi). At 24 hpf, glutamate-cysteine ligase (GCLC) was slightly down-regulated by all congeners evaluated. At 120 hpf, TNF receptor-associated protein 1 (TRAP1) and COX6A were up-regulated by all congeners, however GSTpi was down-regulated by all congeners. The results of quantitative real-time transcription polymerase chain reaction are mixed and do not strongly support a transcriptional response to oxidative stress. According to the authors' data, PBDEs do not induce oxidative stress. Oxidative stress may occur at high exposure concentrations; however, this does not appear to be a primary mechanism of action for the PBDE congeners tested. PMID:25663549

  5. Disposition of toxic PCB congeners in snapping turtle eggs: expressed as toxic equivalents of TCDD

    SciTech Connect

    Bryan, A.M.; Stone, W.B.; Olafsson, P.G.

    1987-11-01

    Studies of snapping turtles, taken from the region of the Upper Hudson River, in New York State, revealed exceedingly high levels of PCBs in the adipose tissue. There is evidence to suggest that large reserves of fat provide protection against chlorinated hydrocarbon toxicity. Such storage may protect snapping turtle eggs from disposition of toxic PCB congeners and account for the apparent absence of reports regarding detrimental effects on the hatchability of eggs from turtles living in the vicinity of the upper Hudson River. The present study was undertaken to determine if indeed these eggs are protected against disposition of toxic PCB congeners by the presence of large reserves of fat. Although tissue volumes play an important role in determining the initial site of disposition, the major factor controlling the elimination of these compounds involves metabolism. For simple halogenated benzenes as well as for more complex halogenated biphenyls, oxidative metabolism catalyzed by P-448, occurs primarily at the site of two adjacent unsubstituted carbon atoms via arene oxide formation leading to the formation of water soluble metabolites. Toxicological studies have demonstrated that the most toxic PCB congeners, isosteriomers of tetrachlorodibenzo-p-dioxin (TCDD), require no metabolic activation. These compounds have chlorine atoms in the meta and para positions of both rings. It may be concluded that the structures of PCB congeners and isomers which favor induction of cytochrome P-448 are also those which are toxic and resist metabolism. It is the objective of the present study to determine if the heavy fat bodies of the female turtle provide a sufficiently large sink to retain the toxic congeners and prevent their incorporation into the eggs.

  6. Comparative Biological Effects and Potency of 17a- and 17ß-Estradiol In Fathead Minnows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol is the most potent natural estrogen commonly found in anthropogenically altered environments and has been the focus of many toxicological laboratory studies. However, fewer aquatic toxicological data on the effects of 17a-estradiol, a diastereoisomer of 17ß-estradiol, exists in the li...

  7. Neurotensin enhances estradiol induced DNA synthesis in immature rat uterus

    SciTech Connect

    Mistry, A.; Vijayan, E.

    1985-05-27

    Systemic administration of Neurotensin, a tridecapeptide, in immature rats treated with estradiol benzoate significantly enhances uterine DNA synthesis as reflected by the incorporation of /sup 3/H-thymidine. The peptide may have a direct action on the uterus. Substance P, a related peptide, had no effect on uterine DNA synthesis. 18 references, 4 tables.

  8. Estradiol valerate and alcohol intake: dose-response assessments

    PubMed Central

    Quirarte, Gina L; Reid, Larry D; de la Teja, I Sofía Ledesma; Reid, Meta L; Sánchez, Marco A; Díaz-Trujillo, Arnulfo; Aguilar-Vazquez, Azucena; Prado-Alcalá, Roberto A

    2007-01-01

    Background An injection of estradiol valerate (EV) provides estradiol for a prolonged period. Recent research indicates that a single 2.0 mg injection of EV modifies a female rat's appetite for alcoholic beverages. This research extends the initial research by assessing 8 doses of EV (from .001 to 2.0 mg/female rat), as well assessing the effects of 2.0 mg EV in females with ovariectomies. Results With the administration of EV, there was a dose-related loss of bodyweight reaching the maximum loss, when it occurred, at about 4 days after injections. Subsequently, rats returned to gaining weight regularly. Of the doses tested, only the 2.0 mg dose produced a consistent increase in intake of ethanol during the time previous research indicated that the rats would show enhanced intakes. There was, however, a dose-related trend for smaller doses to enhance intakes. Rats with ovariectomies showed a similar pattern of effects, to intact rats, with the 2 mg dose. After extensive histories of intake of alcohol, both placebo and EV-treated females had estradiol levels below the average measured in females without a history of alcohol-intake. Conclusion The data support the conclusion that pharmacological doses of estradiol can produce enduring changes that are manifest as an enhanced appetite for alcoholic beverages. The effect can occur among females without ovaries. PMID:17335585

  9. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been...

  10. Fate of glucuronide conjugated estradiol in the environment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fate and transport of conjugated reproductive hormones, which are polar compared to parent hormones, are little understood. Laboratory bench-scale soil (Hamar; Sandy, mixed, frigid typic Endoaquolls) sorption studies were conducted using [14C] 17ß-estradiol-3-glucuronide for a range of concentra...

  11. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Progesterone and estradiol benzoate. 522.1940 Section 522.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL...

  12. Fate of 17B-estradiol in anaerobic lagoon digesters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fate of [14C]17B-estradiol ([14C]E2) was monitored for 42 d in triplicate 10 L anaerobic digesters. Total radioactive residues (TRR) decreased rapidly in the liquid layer of the digesters and reached a steady-state value of 19-24% of the initial dose after 4 days. LC/MS/MS analyses of the liqu...

  13. 21 CFR 862.1260 - Estradiol test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  14. 21 CFR 862.1260 - Estradiol test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  15. 21 CFR 862.1260 - Estradiol test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  16. 21 CFR 862.1260 - Estradiol test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  17. Relative potencies of individual polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners and congener mixtures based on induction of cytochrome P4501A mRNA in a rainbow trout gonadal cell line (RTG-2)

    SciTech Connect

    Zabel, E.W.; Pollenz, R.; Peterson, R.E.

    1996-12-01

    Cytochrome P450-catalyzed enzyme activity in cell culture was investigated as a bioassay for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents in environmental mixtures of polychlorinated dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF), and biphenyl (PCB) congeners. A problem with the use of enzyme induction is that certain congeners are unable to induce P4501A enzyme activity to the same maximal level as TCDD. The authors sought to eliminate this problem by measuring mRNA induction rather than enzyme activity. Rainbow trout gonadal cells (RTG-2) were exposed to PCDD, PCDF, and PCB congeners and congener mixtures, and induction of cytochrome P4501A mRNA was measured. A high level of induction in cells treated with only a medium change was seen and was due to a component of the fresh medium, 2,3,7,8-Substituted PCDD and PCDF congeners and four-non-ortho-substituted PCBs caused significant induction. Toxic equivalency factors determined in RTG-2 cells were generally higher than those in rainbow trout early life stages. Rainbow trout gonadal cell (RTG-2) bioassay TCDD equivalents (TEqs) for three environmental extracts were lower than predicted by addition of individual congener TEqs, and the synthetic congener mixture acted additively.

  18. Toxaphene congeners in the Canadian Great Lakes basin: temporal and spatial food web dynamics.

    PubMed

    Whittle, D M; Kiriluk, R M; Carswell, A A; Keir, M J; MacEachen, D C

    2000-01-01

    Samples of a top predator fish species, lake trout (Salvelinus namaycush) and predominant forage species including smelt (Osmerus mordax), alewife (Alosa pseudoharengus), slimy sculpin (Cottus cognatus), deepwater sculpin (Myoxocephalus quadricornis) and lake herring (Coregonus artedii) were, collected from throughout 4 of the 5 Great Lakes (Superior, Huron, Erie and Ontario) (Fig. 1). Lake trout were also collected from three isolated lake systems (Lakes Nipigon, Simcoe and Opeongo), all located within the basin. All the samples were analysed for body burdens of total toxaphene and 22 toxaphene congeners. In addition, from each of the Great Lakes sites samples of major invertebrate dietary items, which included Mysis relicta, Diporeia hoyi and plankton, were similarly analysed. Whole lake trout samples, archived at -80 degrees C, were reanalysed to determine historical trends of toxaphene congeners plus carbon and nitrogen stable isotope signatures. The Lake Superior food web consistently had the highest levels of total toxaphene of all the Great Lakes monitored. The primary source of toxaphene to Lake Superior has been identified as atmospheric transport and deposition from sites in the southern US, Mexico and Central America (Hoff, R.M., Strachan, W.M.J., Sweet, C.W., Chan, C.H., Shackelton, M., Bidleman, T.F., Brice, K.A., Burnison, D.A., Cussion, S., Gatz, D.F., Harlin, K., Schroeder, W.H., 1996. Atmospheric deposition of toxic chemicals to the Great Lakes: A review of data through 1994. Atmospheric Environ. 30, 3505-3527). Of the offsystem lakes surveyed. Lake Nipigon, situated due north of Lake Superior and with a Lake Basin area of about 6% of Lake Superior (Hendendorf, C.E., 1982. J. Great Lakes Res. 8(3), 379-412) had total toxaphene levels in lake trout equivalent to about 50% of those found in lake trout from Lake Superior. Temporal trend toxaphene congener analysis was conducted on archived whole fish samples collected over the period 1980 through to

  19. The Orientation and Dynamics of Estradiol and Estradiol Oleate in Lipid Membranes and HDL Disc Models

    PubMed Central

    Vogel, Alexander; Scheidt, Holger A.; Feller, Scott E.; Metso, Jari; Badeau, Robert M.; Tikkanen, Matti J.; Wähälä, Kristiina; Jauhiainen, Matti; Huster, Daniel

    2014-01-01

    Estradiol (E2) and E2 oleate associate with high-density lipoproteins (HDLs). Their orientation in HDLs is unknown. We studied the orientation of E2 and E2 oleate in membranes and reconstituted HDLs, finding that E2 and E2 oleate are membrane-associated and highly mobile. Our combination of NMR measurements, molecular dynamics simulation, and analytic theory identifies three major conformations where the long axis of E2 assumes a parallel, perpendicular, or antiparallel orientation relative to the membrane’s z-direction. The perpendicular orientation is preferred, and furthermore, in this orientation, E2 strongly favors a particular roll angle, facing the membrane with carbons 6, 7, 15, and 16, whereas carbons 1, 2, 11, and 12 point toward the aqueous phase. In contrast, the long axis of E2 oleate is almost exclusively oriented at an angle of ∼60° to the z-direction. In such an orientation, the oleoyl chain is firmly inserted into the membrane. Thus, both E2 and E2 oleate have a preference for interface localization in the membrane. These orientations were also found in HDL discs, suggesting that only lipid-E2 interactions determine the localization of the molecule. The structural mapping of E2 and E2 oleate may provide a design platform for specific E2-HDL-targeted pharmacological therapies. PMID:24988346

  20. Correlation between human maternal-fetal placental transfer and molecular weight of PCB and dioxin congeners/isomers.

    PubMed

    Mori, Chisato; Nakamura, Noriko; Todaka, Emiko; Fujisaki, Takeyoshi; Matsuno, Yoshiharu; Nakaoka, Hiroko; Hanazato, Masamichi

    2014-11-01

    Establishing methods for the assessment of fetal exposure to chemicals is important for the prevention or prediction of the child's future disease risk. In the present study, we aimed to determine the influence of molecular weight on the likelihood of chemical transfer from mother to fetus via the placenta. The correlation between molecular weight and placental transfer rates of congeners/isomers of polychlorinated biphenyls (PCBs) and dioxins was examined. Twenty-nine sample sets of maternal blood, umbilical cord, and umbilical cord blood were used to measure PCB concentration, and 41 sample sets were used to analyze dioxins. Placental transfer rates were calculated using the concentrations of PCBs, dioxins, and their congeners/isomers within these sample sets. Transfer rate correlated negatively with molecular weight for PCB congeners, normalized using wet and lipid weights. The transfer rates of PCB or dioxin congeners differed from those of total PCBs or dioxins. The transfer rate for dioxin congeners did not always correlate significantly with molecular weight, perhaps because of the small sample size or other factors. Further improvement of the analytical methods for dioxin congeners is required. The findings of the present study suggested that PCBs, dioxins, or their congeners with lower molecular weights are more likely to be transferred from mother to fetus via the placenta. Consideration of chemical molecular weight and transfer rate could therefore contribute to the assessment of fetal exposure.

  1. ESTRADIOL AND THE ESTRADIOL METABOLITE, 2-HYDROXYESTRADIOL, ACTIVATE AMP-ACTIVATED PROTEIN KINASE IN C2C12 MYOTUBES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Systemic loss of estradiol (E2) during menopause is associated with increased adiposity which can be prevented with E2 replacement. Rodent studies suggest that E2, or lack of, is a key mediator in menopause-related metabolic changes. We have previously demonstrated that E2 treatment produces a rap...

  2. Induction of heme oxygenase-1 by whisky congeners in human endothelial cells.

    PubMed

    Suzuki, Keiko; Nemoto, Asuka; Tanaka, Izumi; Koshimizu, Seiichi; Suwa, Yoshihide; Ishihara, Hiroshi

    2010-08-01

    It is expected that the production of the cytoprotective heme oxygenase-1 (HO-1) protein in endothelial cells would reduce severity of vascular injuries, while phenolic compounds are known to induce HO-1 mRNA and protein in various cells. We investigated the activation of HO-1 by whisky, which contains various phenolic substances. The congeners of whisky stored from 4 to 18 y in oak barrels were shown to induce an increase of HO-1 protein in human umbilical vein endothelial cells, while those of freshly distilled whisky spirit exhibited no activity. To determine the compounds with potent HO-1-inducing activity among the whisky congeners, several chemicals that had been reported to exist in whisky or oak barrels were screened, and coniferyl aldehyde and sinapyl aldehyde showed the activity. Thus, compounds that emerged in whisky during barrel storage induced cytoprotective protein, HO-1, in human endothelial cells.

  3. Polychlorinated biphenyl (PCB) congener effects on the longevity of the housefly

    SciTech Connect

    Tehseen, W.M.; Hansen, L.G.; Schaeffer, D.J. )

    1992-01-01

    The microsomal monooxygenase system in the housefly is well-characterized, active, inducible and inhibited by the same types of compounds as in vertebrate systems. Flies metabolize PCBs to polar products and retain congeners from a commercial mixture in proportions consistent with PCB biotransformation and elimination in vertebrates. Although TCDD has been shown to have a high affinity for, and be an effective agonist of the juvenile hormone receptor in insects, toxic manifestations in adult insects may differ from those in certain highly sensitive vertebrate species. This study was undertaken to determine if the housefly bioassay could effectively compare the net adverse biological activity of a group of PCB congeners independent of Ah receptor effects.

  4. Novel chemistry of invasive plants: exotic species have more unique metabolomic profiles than native congeners.

    PubMed

    Macel, Mirka; de Vos, Ric C H; Jansen, Jeroen J; van der Putten, Wim H; van Dam, Nicole M

    2014-07-01

    It is often assumed that exotic plants can become invasive when they possess novel secondary chemistry compared with native plants in the introduced range. Using untargeted metabolomic fingerprinting, we compared a broad range of metabolites of six successful exotic plant species and their native congeners of the family Asteraceae. Our results showed that plant chemistry is highly species-specific and diverse among both exotic and native species. Nonetheless, the exotic species had on average a higher total number of metabolites and more species-unique metabolites compared with their native congeners. Herbivory led to an overall increase in metabolites in all plant species. Generalist herbivore performance was lower on most of the exotic species compared with the native species. We conclude that high chemical diversity and large phytochemical uniqueness of the exotic species could be indicative of biological invasion potential. PMID:25077026

  5. Novel chemistry of invasive plants: exotic species have more unique metabolomic profiles than native congeners

    PubMed Central

    Macel, Mirka; de Vos, Ric C H; Jansen, Jeroen J; van der Putten, Wim H; van Dam, Nicole M

    2014-01-01

    It is often assumed that exotic plants can become invasive when they possess novel secondary chemistry compared with native plants in the introduced range. Using untargeted metabolomic fingerprinting, we compared a broad range of metabolites of six successful exotic plant species and their native congeners of the family Asteraceae. Our results showed that plant chemistry is highly species-specific and diverse among both exotic and native species. Nonetheless, the exotic species had on average a higher total number of metabolites and more species-unique metabolites compared with their native congeners. Herbivory led to an overall increase in metabolites in all plant species. Generalist herbivore performance was lower on most of the exotic species compared with the native species. We conclude that high chemical diversity and large phytochemical uniqueness of the exotic species could be indicative of biological invasion potential. PMID:25077026

  6. Accumulation and depletion of polychlorinated biphenyl (PCB) congeners in the housefly (musca domestica, L. )

    SciTech Connect

    Hansen, L.G. ); Storr-Hansen, E. )

    1992-01-01

    Polychlorinated biphenyl (PCB) residues in food chains and in the environment are dynamic complex mixtures and there is considerable interest in the disposition as well as toxicities of individual congeners. The persistence and biological activities of PCBs are intimately associated with microsomal monooxygenases. The house fly, Musca domestica (L.), has long been a standard organism for studies of pesticide toxicology and has an active and well-defined microsomal monooxygenase system. These oxidases in the fly can be induced by PCBs. It was considered of interest to provide data which may indicate whether or not the relatively large and mobile biomass of insects in general may play a role in the global disposition of PCBs. It was also of interest to determine if the house fly could serve as a model for determining the relative accumulation, elimination, and toxicities of individual PCB congeners.

  7. Polychlorinated biphenyl congeners in the aquatic environment of the Mekong River, South of Vietnam.

    PubMed

    Carvalho, Fernando P; Villeneuve, J-P; Cattini, C; Thuan, Dao Dinh; Nhan, Dang Duc

    2009-12-01

    Polychlorinated biphenyl compounds (PCBs) were analyzed in sediments and clams' soft tissues from sampling sites in the Mekong River delta from the border with Cambodia to the coast of South China Sea. Concentrations of 13 individual PCB congeners are reported. Median concentration of SigmaPCB congeners was 0.279 ng g(-1) dry weight (range 0.106-2.016 ng g(-1) dry weight) in sediments, and 5.20 ng g(-1) dry weight (range 1.89-19.37 ng g(-1)) in clams. Distribution and bioaccumulation of PCBs in the delta are discussed. It is concluded that in the Mekong River delta PCB concentrations were generally lower than in other regions of Vietnam and their likely sources have been waste discharges from repair workshops and other facilities in the delta cities.

  8. Germ-line reinsertions of AKR murine leukemia virus genomes in Akv-1 congenic mice.

    PubMed

    Rowe, W P; Kozak, C A

    1980-08-01

    Congenic mouse strains NIH,Akv-1 and NIH,Akv-2 carry the two high ecotropic virus-inducing loci of the AKR mouse on the NIH Swiss genetic background. Progeny tests of animals in three separate congenic families show that both Avk-1 and Akv-2 are stably transmitted as classical mendelian loci in these mice. However, during the process of inbreeding, additional chromosomal viral loci were detected in several NIH.Akv-1 sublines. These loci appeared only in the progeny of virus-positive females. They segregate with mendelian ratios, are unlinked to markers on chromsome 7 near Akv-1, and are phenotypically expressed as high-virus-inducing loci. The generation of new loci for viurs induction, no doubt resulting from the rare germ-line reintegration of the endogenous ectropic provirus, represents a unique form of gene duplication and rearrangement.

  9. Label-free aptamer-based electrochemical impedance biosensor for 17β-estradiol.

    PubMed

    Lin, Zhenyu; Chen, Lifen; Zhang, Guiyun; Liu, Qida; Qiu, Bin; Cai, Zongwei; Chen, Guonan

    2012-02-21

    A novel aptamer-based label-free electrochemical impedance spectroscopy biosensor for 17β-estradiol has been fabricated. The aptamers were firstly immobilized on the gold electrode through Au-S interaction; the aptamer probe was then bound with the addition of 17β-estradiol to form the estradiol/aptamer complex on the electrode surface. This leads to a significantly larger interfacial electron transfer resistance than that without the addition of 17β-estradiol. The change in the resistance had a linear relationship with 17β-estradiol concentration in the range of 1.0 × 10(-8) to 1.0 × 10(-11) mol L(-1), with a detection limit of 2.0 × 10(-12) mol L(-1). The biosensor showed high selectivity to 17β-estradiol and good stability. The designed biosensor has been applied to detect 17β-estradiol in human urine with satisfactory results.

  10. In silico predictive studies of mAHR congener binding using homology modelling and molecular docking.

    PubMed

    Panda, Roshni; Cleave, A Suneetha Susan; Suresh, P K

    2014-09-01

    The aryl hydrocarbon receptor (AHR) is one of the principal xenobiotic, nuclear receptor that is responsible for the early events involved in the transcription of a complex set of genes comprising the CYP450 gene family. In the present computational study, homology modelling and molecular docking were carried out with the objective of predicting the relationship between the binding efficiency and the lipophilicity of different polychlorinated biphenyl (PCB) congeners and the AHR in silico. Homology model of the murine AHR was constructed by several automated servers and assessed by PROCHECK, ERRAT, VERIFY3D and WHAT IF. The resulting model of the AHR by MODWEB was used to carry out molecular docking of 36 PCB congeners using PatchDock server. The lipophilicity of the congeners was predicted using the XLOGP3 tool. The results suggest that the lipophilicity influences binding energy scores and is positively correlated with the same. Score and Log P were correlated with r = +0.506 at p = 0.01 level. In addition, the number of chlorine (Cl) atoms and Log P were highly correlated with r = +0.900 at p = 0.01 level. The number of Cl atoms and scores also showed a moderate positive correlation of r = +0.481 at p = 0.01 level. To the best of our knowledge, this is the first study employing PatchDock in the docking of AHR to the environmentally deleterious congeners and attempting to correlate structural features of the AHR with its biochemical properties with regards to PCBs. The result of this study are consistent with those of other computational studies reported in the previous literature that suggests that a combination of docking, scoring and ranking organic pollutants could be a possible predictive tool for investigating ligand-mediated toxicity, for their subsequent validation using wet lab-based studies.

  11. Inhalation and Dietary Exposure to PCBs in Urban and Rural Cohorts via Congener-Specific Measurements

    PubMed Central

    2015-01-01

    Polychlorinated biphenyls (PCBs) are a group of 209 persistent organic pollutants, whose documented carcinogenic, neurological, and respiratory toxicities are expansive and growing. However, PCB inhalation exposure assessments have been lacking for North American ambient conditions and lower-chlorinated congeners. We assessed congener-specific inhalation and dietary exposure for 78 adolescent children and their mothers (n = 68) in the Airborne Exposure to Semi-volatile Organic Pollutants (AESOP) Study. Congener-specific PCB inhalation exposure was modeled using 293 measurements of indoor and outdoor airborne PCB concentrations at homes and schools, analyzed via tandem quadrupole GS-MS/MS, combined with questionnaire data from the AESOP Study. Dietary exposure was modeled using Canadian Total Diet Survey PCB concentrations and National Health and Nutrition Examination Survey (NHANES) food ingestion rates. For ∑PCB, dietary exposure dominates. For individual lower-chlorinated congeners (e.g., PCBs 40+41+71, 52), inhalation exposure was as high as one-third of the total (dietary+inhalation) exposure. ∑PCB inhalation (geometric mean (SE)) was greater for urban mothers (7.1 (1.2) μg yr–1) and children (12.0 (1.2) μg yr–1) than for rural mothers (2.4 (0.4) μg yr–1) and children (8.9 (0.3) μg yr–1). Schools attended by AESOP Study children had higher indoor PCB concentrations than did homes, and account for the majority of children’s inhalation exposure. PMID:25510359

  12. Investigations into the effects of PCB congeners on reproduction in lake trout from the Great Lakes

    USGS Publications Warehouse

    Mac, Michael J.; Schwartz, T.R.

    1992-01-01

    Eggs of feral lake trout collected in Lake Michigan were reared under laboratory conditions and monitored for egg hatchability, physical abnormalities, and survival of fry. Subsamples of eggs were also analyzed for PCB congeners. A negative correlation was found between egg hatchability and total PCBs but expressing PCB dose as dioxin equivalents did not produce as strong a correlation. No other measure of reproductive success correlated significantly with PCB concentration in the egg.

  13. Polychlorinated biphenyls and breast cancer: A congener-specific meta-analysis.

    PubMed

    Leng, Ling; Li, Jing; Luo, Xiu-mei; Kim, Jun-young; Li, Yi-meng; Guo, Xue-mei; Chen, Xi; Yang, Qiao-yun; Li, Guang; Tang, Nai-jun

    2016-03-01

    The incidence of breast cancer is related to various risk factors, especially that the environmental and lifestyle factors account for major contribution at the rate of 70% to 95% over all. However, there still remains some controversy over the epidemiological evidence regarding the effects of environmental carcinogens on the risk of breast cancer. We conducted a quantitative meta-analysis aiming at full evaluation of the effects of polychlorinated biphenyls (PCBs) on breast cancer in a congener-specific fashion. Four online literature databases were systematically searched before 1st January 2015, for studies stating correlation between PCB congeners and breast cancer. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies that were included in our analysis. Sixteen studies were included in our final meta-analysis after screening based on the priori inclusion criteria. Nine PCB congeners were reported by more than two studies and they were presented in detail. The pooled Odds Ratios (ORs) showed a significant increase in the risk of breast cancer in individuals with higher plasma/fat levels of PCB 99 (OR: 1.36; 95% CI: 1.02 to 1.80), PCB 183 (OR: 1.56; 95% CI: 1.25 to 1.95) and PCB 187 (OR: 1.18; 95% CI: 1.01 to 1.39). Besides, the outcomes did not support a relationship between dioxin-like PCB congeners and the risk of breast cancer. The results of our meta-analysis imply that PCB 99, PCB 183 and PCB 187 would increase the risk of breast cancer. The mechanism of this increased risk may be by the induction of the CYP2B family in cytochrome P450 enzymes.

  14. An invasive dandelion unilaterally reduces the reproduction of a native congener through competition for pollination.

    PubMed

    Kandori, Ikuo; Hirao, Toshihiro; Matsunaga, Satoshi; Kurosaki, Tsutomu

    2009-03-01

    The impact of invasive alien species on native species is of increasing global concern. Invasive plants have various negative effects on natives through competition; however, relatively little is known about competition for pollination. The relationship between Japanese native dandelions (Taraxacum spp.) and invasive congeners may be a typical case of such an interaction. For example, native dandelions are being replaced by invasive congeners, especially in urban and suburban areas of Japan. To explain this phenomenon, we hypothesized that when natives are mixed with attractive invasives, natives may suffer from reduced seed set because invasives deprive natives of pollinators or because pollinators frequently move between species, resulting in interspecific pollen transfer. To test this hypothesis, we studied the effect of the invasive dandelion T. officinale on the pollination and seed set of the native T. japonicum using artificial arrays of monospecific and mixed-species plots as well as natural populations. Taraxacum officinale attracted more pollinator visits, perhaps because it produced more nectar than T. japonicum. The number of pollinator visits to T. japonicum was reduced when the congeners were grown together, and pollinators moved frequently between the two species. The proportion of seed set for T. japonicum was reduced in the presence of T. officinale in both artificial arrays and natural populations. These results support our hypothesis that interspecific competition for pollination plays an important role in the recent replacement of native dandelions by invasive congeners in Japan. Because invasive dandelions are apomicts, negative effects are incurred only by sexual natives. Thus, this system can be recognized as a rare case of interspecific interaction through pollination.

  15. Relationship between ovarian reserve and preovulatory estradiol during a fixed-time AI protocol in beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estradiol production is essential for reproductive efficiency. This study compared numbers of follicles in beef cows that did or did not have elevated preovulatory estradiol during a fixed-time AI (FTAI) protocol. In experiment 1, 5 low estradiol (LowE2) and 5 high estradiol (HighE2) cows were slaug...

  16. PCB patterns in herring and pike with special regard to co-planar congeners

    SciTech Connect

    Alsberg, T.; Wit, C. de; Eriksson, U.; Jaernberg, U.; Bignert, A.; Olsson, M.

    1995-12-31

    This study investigates the patterns of PCB in two aquatic organisms, herring and pike. The aim is to establish a basis for a model for estimating the levels of co-planar PCBs from the concentrations of nonplanar congeners. The chosen fish populations reflect differences in species, age, habitat (locations) and time of catch, as well as differences in total PCB concentrations. More stable patterns would be presumed, the more homogeneous the population. Herring were sampled at two locations, one in the Bothnian Bay (Harufjaerden) and one in the Southern Baltic (Utlaengan). Two age classes were sampled at each location, 2- and 6-year olds, respectively at Utlaengan, and 2- and 5-year olds, respectively at Harufjaerden. Pike were sampled from Lake Bolmen in southern Sweden in 1992, and pike from the same location but sampled in 1971 were taken from the specimen bank. Ten individuals per population were analyzed. Thirteen PCB congeners were determined, namely PCBs 28, 52, 77, 101, 105, 118, 126, 1 38, 153, 156, 157, 169, 180, thus including the seven PCBs that are measured in the national monitoring program, in addition to three monoortho and three non-ortho PCBs. Regarding the possibility of creating a model for calculating the concentrations of the planar PCBs from those of the non-planar, the results look promising for PCB-126 and PCB-169, whereas PCB-77 shows a lower correlation to the non-planar congeners.

  17. Profiles of polychlorinated biphenyl congeners, organochlorine pesticides, and butyltins in southern sea otters and their prey.

    PubMed

    Kannan, Kurunthachalam; Kajiwara, Natsuko; Watanabe, Mafumi; Nakata, Haruhiko; Thomas, Nancy J; Stephenson, Mark; Jessup, David A; Tanabe, Shinsuke

    2004-01-01

    Concentrations of organochlorine pesticides, polychlorinated biphenyl (PCB) congeners, and butyltins were measured in sea otters and selected prey species (invertebrates) collected from the California (USA) coast. Polychlorinated biphenyls, DDTs (sum of p,p'-dichlorodiphenyldichloroethylene [p,p'-DDE], p,p'-dichlorodiphenyldichloroethane [p,p'-DDD], and p,p'-DDT), and butyltins were the major contaminants found in sea otters and their prey. Lipid-normalized concentrations of PCBs and DDT in sea otter livers were 60- and 240-fold greater than those found in the prey. Great biomagnification of PCBs and DDT in sea otters is suggested to result from their high per-capita intake of diet compared with those of other marine mammals. Profiles of PCB congeners in sea otters and prey species suggest a great capacity of sea otters to biotransform lower-chlorinated congeners. Sea otters seem to possess a greater ability than cetaceans to metabolize PCBs. The 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents of non- and mono-ortho PCBs in sea otters and certain prey species were at or above the theoretical threshold for toxic effects.

  18. Bioaccumulation profiles of polychlorinated biphenyl congeners and organochlorine pesticides in Ganges River dolphins

    SciTech Connect

    Senthilkumar, K.; Kannan, K.; Sinha, R.K.; Tanabe, S.; Giesy, J.P.

    1999-07-01

    Isomer-specific concentrations of polychlorinated biphenyls (PCBs) including non-, mono-, and di-ortho-substituted congeners, DDT and its metabolites, hexachlorocyclohexane (HCH) isomers, chlordane compounds, and hexachlorobenzene (HCB) were determined in river dolphin blubber and prey fishes collected during 1993 through 1996 from the River Ganges in India. Concentrations of organochlorines were also measured in the milk and liver of dolphins, benthic invertebrates, and sediments. The DDTs and PCBs were the predominant compounds found in dolphin tissues and fish that comprise the diet of dolphins. Concentrations of DDTs and PCBs in the blubber of dolphins were in the range of 30 to 120 and 1.5 to 25 {micro}g/g, lipid weight, respectively. Penta- and hexachlorobiphenyls collectively accounted for 68 to 80% of the total PCB concentrations in river dolphins. Hexachlorobiphenyl congener 138 (2.2{prime}, 3,4,4{prime},5{prime}-) was the most abundant in dolphin blubber and prey fishes. The isomer/congener pattern of PCBs and organchlorine pesticides suggested that there is less metabolism due to cytochrome P450 enzymes in Ganges river dolphins than in marine or terrestrial mammals. The mean 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) estimated in river dolphin blubber was greater than those that can cause adverse effects in mink. Comparison of organochlorine concentrations in river dolphins with those of the values reported for samples analyzed during 1988 through 1992 suggested that the contamination by these compounds has increased in the River Ganges.

  19. Profiles of polychlorinated biphenyl congeners, organochlorine pesticides and butlyns in southern sea otters and their prey

    USGS Publications Warehouse

    Kannan, K.; Kajiwara, N.; Watanabe, M. E.; Nakata, H.; Thomas, N.J.; Stephenson, M.; Jessup, David A.; Tanabe, S.

    2004-01-01

    Concentrations of organochlorine pesticides, polychlorinated biphenyl (PCB) congeners, and butyltins were measured in sea otters and selected prey species (invertebrates) collected from the California (USA) coast. Polychlorinated biphenyls, DDTs (sum of p,pa??-dichlorodiphenyldichloroethylene [p,pa??-DDE], p,pa??-dichlorodiphenyldichloroethane [p,pa??-DDD], and p,pa??-DDT), and butyltins were the major contaminants found in sea otters and their prey. Lipid-normalized concentrations of PCBs and DDT in sea otter livers were 60- and 240-fold greater than those found in the prey. Great biomagnification of PCBs and DDT in sea otters is suggested to result from their high per-capita intake of diet compared with those of other marine mammals. Profiles of PCB congeners in sea otters and prey species suggest a great capacity of sea otters to biotransform lower-chlorinated congeners. Sea otters seem to possess a greater ability than cetaceans to metabolize PCBs. The 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents of non- and mono-ortho PCBs in sea otters and certain prey species were at or above the theoretical threshold for toxic effects.

  20. Exposure to mercury and Aroclor 1268 congeners in least terns (Sternula antillarum) in coastal Georgia, USA.

    PubMed

    Robinson, Gabrielle L; Mills, Gary L; Lindell, Angela H; Schweitzer, Sara H; Hernandez, Sonia M

    2015-08-01

    Concentrations of total mercury and the rare PCB mixture Aroclor 1268 in least terns (Sternula antillarum), a colonially-nesting, piscivorous seabird, in the Turtle River estuary and other coastal sites in Georgia, USA, were investigated. The Turtle River estuary is the location of the Linden Chemical Plant (LCP) Superfund site, a site prioritized by USA law for immediate remediation, where industries released effluent containing these contaminants until 1994. Aroclor 1268 is a highly-chlorinated PCB mixture that was used and released exclusively at the LCP site and nowhere else in the south eastern USA. High concentrations of Aroclor 1268 congeners and mercury have been documented in biota local to LCP, but no studies report concentrations in high trophic level, piscivorous birds such as least terns. We collected feathers and feces from chicks, and eggs from adults, at nesting colonies along the Georgia coast to analyze contaminant loads (in dry weight ppb). Mean Aroclor 1268 mixture concentrations in eggs (≤16,329 ppb) were highest at colonies in and just outside LCP, and decreased with increasing distance (up to 110 km) from LCP, but the Aroclor 1268 signature congener mixture was present at all sites. Mercury concentrations in eggs (≤3370 ppb), feathers (≤5950 ppb), and feces (≤417 ppb), were present at all sites, but did not vary significantly among sites. This report confirms the extensive dispersal of Aroclor 1268 congeners (approximately 110 km north and 70 km south of its point source) via bioaccumulation and trophic transfer. PMID:26166752

  1. Coplanar polychlorinated biphenyl congeners in shark livers from the north-western African Atlantic ocean

    SciTech Connect

    Serrano, R.; Fernandez, M.A.; Hernandez, L.M.

    1997-01-01

    Polychlorinated biphenyls have been widely used by industry throughout the world since 1930. Although their use has been banned in many countries since the late 1970s, they still represent an important class of priority pollutants due to their persistence. Most open uses of these chemicals have been severely curtailed in industrialized nations, but a considerable fraction of past productions is probably still cycling in the ecosphere. In recent years, attention has been focused on the toxicity of PCBs, especially of those congeners showing similar toxicity as the polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDFs). It has been shown that PCB congeners` toxicity largely depends on the chlorine substitution pattern. The most toxic PCB cogeners are those with two para chlorines, at least two meta chlorines and 0-2 ortho chlorines. These so-called {open_quotes}coplanar{close_quotes} (non- mono- and di-ortho) PCB cogeners are able to obtain planar conformation. Recently, toxic equivalence factors have been assigned to coplanar PCBs. Thus determination of individual PCB cogeners is important for evaluating the toxic potentials of PCB residues in, for example, wildlife. This paper presents preliminary results of a study looking at levels of PCB congeners, including coplanar ones, in the liver of six shark species, collected in the North African Atlantic Ocean. 15 refs., 2 figs., 2 tabs.

  2. Distinguishing PCB Isomeric Congeners with their Gas Chromatographic and Mass Spectrometric Ortho Effect using Comprehensive Gas Chromatography

    EPA Science Inventory

    The 209 polychlorinated biphenyl (PCB) congeners and associated nine isomeric groups (nine groups of PCBs with the same degree of chlorination) have been long recorded as high endocrine disrupting chemicals in the environment. Difficult analytical problems exist, in those frequen...

  3. Endocrine disrupter--estradiol--in Chesapeake Bay tributaries.

    PubMed

    Dorabawila, Nelum; Gupta, Gian

    2005-04-11

    Exogenous chemicals that interfere with natural hormonal functions are considered endocrine disrupting chemicals (EDCs). Estradiol (17beta-estradiol or E2) is the most potent of all xenoestrogens. Induction of vitellogenin (VTG) production in male fish occurs at E2 concentrations as low as 1 ng l-1. E2 reaches aquatic systems mainly through sewage and animal waste disposal. Surface water samples from ponds, rivers (Wicomico, Manokin and Pocomoke), sewage treatment plants (STPs), and coastal bays (Assawoman, Monie, Chincoteague, and Tangier Sound-Chesapeake Bay) on the Eastern Shore of Maryland were analyzed for E2 using enzyme linked immuno-sorbent assay (ELISA). E2 concentrations in river waters varied between 1.9 and 6.0 ng l-1. Highest E2 concentrations in river waters were observed immediately downstream of STPs. E2 concentrations in all the coastal bays tested were 2.3-3.2 ng l-1. PMID:15811666

  4. Estradiol modulates Kiss1 neuronal response to ghrelin

    PubMed Central

    Frazao, Renata; Lemko, Heather M. Dungan; da Silva, Regina P.; Ratra, Dhirender V.; Lee, Charlotte E.; Williams, Kevin W.; Zigman, Jeffrey M.

    2014-01-01

    Ghrelin is a metabolic signal regulating energy homeostasis. Circulating ghrelin levels rise during starvation and fall after a meal, and therefore, ghrelin may function as a signal of negative energy balance. Ghrelin may also act as a modulator of reproductive physiology, as acute ghrelin administration suppresses gonadotropin secretion and inhibits the neuroendocrine reproductive axis. Interestingly, ghrelin's effect in female metabolism varies according to the estrogen milieu predicting an interaction between ghrelin and estrogens, likely at the hypothalamic level. Here, we show that ghrelin receptor (GHSR) and estrogen receptor-α (ERα) are coexpressed in several hypothalamic sites. Higher levels of circulating estradiol increased the expression of GHSR mRNA and the co-xpression of GHSR mRNA and ERα selectively in the arcuate nucleus (ARC). Subsets of preoptic and ARC Kiss1 neurons coexpressed GHSR. Increased colocalization was observed in ARC Kiss1 neurons of ovariectomized estradiol-treated (OVX + E2; 80%) compared with ovariectomized oil-treated (OVX; 25%) mice. Acute actions of ghrelin on ARC Kiss1 neurons were also modulated by estradiol; 75 and 22% of Kiss1 neurons of OVX + E2 and OVX mice, respectively, depolarized in response to ghrelin. Our findings indicate that ghrelin and estradiol may interact in several hypothalamic sites. In the ARC, high levels of E2 increase GHSR mRNA expression, modifying the colocalization rate with ERα and Kiss1 and the proportion of Kiss1 neurons acutely responding to ghrelin. Our findings indicate that E2 alters the responsiveness of kisspeptin neurons to metabolic signals, potentially acting as a critical player in the metabolic control of the reproductive physiology. PMID:24473434

  5. Determination of estriol, estradiol, estrone, and progesterone in cosmetic products.

    PubMed

    Hubinger, Jean C

    2015-01-01

    This report describes the development and validation of a reverse phase high-performance liquid chromatography (HPLC) method with UV detection for the determination of the hormones estriol, estradiol, estrone, and progesterone in topically applied products. The developed method was then used to conduct a postmarket survey of consumer products for these hormones. Each product was first mixed with Celite and then extracted with methanol. Extracts were cleaned on a Waters Oasis HLB solid phase extraction cartridge, and then analyzed using reversed phase HPLC. The analytes were separated using an Agilent Zorbax Eclipse XDB C8 (5 μm, 250 mm by 4.6 mm) analytical column and detected by their absorbance at 230 nm. Chromatographic separation was achieved by a 1.0-ml/min linear gradient from 30% acetonitrile and 70% water to 80% acetonitrile and 20% water over 30 min. A final 5 min hold time and a re-equilibration time of 10 min were used to prepare the column for subsequent analysis. Recovery from two different brand lotions spiked with three different levels of estriol, estradiol, estrone, and progesterone ranged from 81.8% to 101%. In this study, a total of 70 cosmetic products were surveyed. Twenty two (63%) of the 35 products were labeled as containing an estrogen and/ or progesterone and also provided quantitative label information about the hormone ingredient. The most frequently labeled hormones were progesterone (66%), estriol (46%), estradiol (11%), and estrone (6%). Six products labeled as containing estriol were found to contain estradiol. An estrogen and/or progesterone were found in 34 products at concentrations ranging from 86.0 to 26,800 μg/g. Progesterone was not found in one product labeled as containing this hormone. An additional 35 products, which did not list hormones on their labels, were analyzed and estrogen or progesterone was not detected in these products. PMID:26454975

  6. Transdermal estradiol treatment during breastfeeding: maternal and infant serum concentrations.

    PubMed

    Pinheiro, Emily; Bogen, Debra L; Hoxha, Denada; Wisner, Katherine L

    2016-04-01

    We examined estradiol (E2) and estrone (E1) concentrations in breastfeeding mother-infant dyads. The mothers had postpartum depression and were participants in a randomized clinical trial with three treatments (transdermal E2, sertraline, and placebo). Neither infant E1 and E2 concentrations nor infant growth differed across the treatments. Transdermal E2 administration of 50 to 200 mcg/day for breastfeeding women did not affect infant E1 or E2 concentrations or infant growth. PMID:25956588

  7. Actions and interactions of estradiol and glucocorticoids in cognition and the brain: Implications for aging women.

    PubMed Central

    Herrera, Alexandra Ycaza; Mather, Mara

    2015-01-01

    Menopause involves dramatic declines in estradiol production and levels. Importantly, estradiol and the class of stress hormones known as glucocorticoids exert countervailing effects throughout the body, with estradiol exerting positive effects on the brain and cognition, glucocorticoids exerting negative effects on the brain and cognition, and estradiol able to mitigate negative effects of glucocorticoids. Although the effects of these hormones in isolation have been extensively studied, the effects of estradiol on the stress response and the neuroprotection offered against glucocorticoid exposure in humans are less well known. Here we review evidence suggesting that estradiol-related protection against glucocorticoids mitigates stress-induced interference with cognitive processes. Animal and human research indicates that estradiol-related mitigation of glucocorticoid damage and interference is one benefit of estradiol supplementation during peri-menopause or soon after menopause. The evidence for estradiol-related protection against glucocorticoids suggests that maintaining estradiol levels in post-menopausal women could protect them from stress-induced declines in neural and cognitive integrity. PMID:25929443

  8. Actions and interactions of estradiol and glucocorticoids in cognition and the brain: Implications for aging women.

    PubMed

    Ycaza Herrera, Alexandra; Mather, Mara

    2015-08-01

    Menopause involves dramatic declines in estradiol production and levels. Importantly, estradiol and the class of stress hormones known as glucocorticoids exert countervailing effects throughout the body, with estradiol exerting positive effects on the brain and cognition, glucocorticoids exerting negative effects on the brain and cognition, and estradiol able to mitigate negative effects of glucocorticoids. Although the effects of these hormones in isolation have been extensively studied, the effects of estradiol on the stress response and the neuroprotection offered against glucocorticoid exposure in humans are less well known. Here we review evidence suggesting that estradiol-related protection against glucocorticoids mitigates stress-induced interference with cognitive processes. Animal and human research indicates that estradiol-related mitigation of glucocorticoid damage and interference is one benefit of estradiol supplementation during peri-menopause or soon after menopause. The evidence for estradiol-related protection against glucocorticoids suggests that maintaining estradiol levels in post-menopausal women could protect them from stress-induced declines in neural and cognitive integrity.

  9. Estradiol and cortisol interactions in youth externalizing psychopathology.

    PubMed

    Tackett, Jennifer L; Reardon, Kathleen W; Herzhoff, Kathrin; Page-Gould, Elizabeth; Harden, K Paige; Josephs, Robert A

    2015-05-01

    Growing evidence has indicated that gonadal and stress hormones interact to shape socially dominant behavior and externalizing psychopathology; however, such work to date has focused exclusively on the testosterone-cortisol interaction, despite expectations that estradiol should be associated with similar behavioral outcomes to testosterone. Here, we present the first empirical test of the hypothesis that adolescent males and females (N=105, ages 13-18) with high estradiol and low cortisol concentrations are at highest risk for externalizing problems, but - replicating previous work - only among adolescents high on pathological personality traits. Parents reported on youth psychopathology and personality, and hormone concentrations were measured via passive drool. Results confirmed the hypothesis: high estradiol was associated with more externalizing behaviors, but only when cortisol was low and personality traits of disagreeableness and emotional instability were high. Further, these associations held when controlling for testosterone concentrations. These findings provide the first empirical evidence of a hypothalamic pituitary adrenal (HPA)×hypothalamic pituitary gonadal (HPG) axis interaction that extends the "dual hormone" hypothesis beyond testosterone.

  10. Estradiol: a rhythmic, inhibitory, indirect control of meal size.

    PubMed

    Eckel, Lisa A

    2004-08-01

    The classic analyses of the inhibitory effects of cholecystokinin (CCK) on meal size, conducted by Professor Gerard P. Smith and his colleagues at the Bourne Laboratory, inspired my initial interest in this field. My current research, which investigates the role of estradiol in the control of meal size, continues to be guided by Gerry's thoughtful, scientific approach to the study of ingestive behavior. In 1996, the year I arrived as a Postdoctoral Fellow at the Bourne Laboratory, Gerry published a new theory of the controls of meal size. In this important paper, Gerry proposed that the controls of meal size can be either direct or indirect. He argued that direct controls of meal size interact with peripheral, preabsorptive receptors that are sensitive to the chemical, mechanical, and colligative properties of ingested food and that indirect controls of meal size function to modulate the activity of direct controls. The purpose of this review is to illustrate how Gerry's theory has guided much of what is known about the mechanism by which estradiol inhibits food intake in female rats. I will provide evidence, primarily from behavioral studies of gonadally intact and ovariectomized rats, that estradiol exerts phasic and tonic inhibitory effects on food intake by acting as a rhythmic, inhibitory, indirect control of meal size.

  11. Estradiol and cortisol interactions in youth externalizing psychopathology.

    PubMed

    Tackett, Jennifer L; Reardon, Kathleen W; Herzhoff, Kathrin; Page-Gould, Elizabeth; Harden, K Paige; Josephs, Robert A

    2015-05-01

    Growing evidence has indicated that gonadal and stress hormones interact to shape socially dominant behavior and externalizing psychopathology; however, such work to date has focused exclusively on the testosterone-cortisol interaction, despite expectations that estradiol should be associated with similar behavioral outcomes to testosterone. Here, we present the first empirical test of the hypothesis that adolescent males and females (N=105, ages 13-18) with high estradiol and low cortisol concentrations are at highest risk for externalizing problems, but - replicating previous work - only among adolescents high on pathological personality traits. Parents reported on youth psychopathology and personality, and hormone concentrations were measured via passive drool. Results confirmed the hypothesis: high estradiol was associated with more externalizing behaviors, but only when cortisol was low and personality traits of disagreeableness and emotional instability were high. Further, these associations held when controlling for testosterone concentrations. These findings provide the first empirical evidence of a hypothalamic pituitary adrenal (HPA)×hypothalamic pituitary gonadal (HPG) axis interaction that extends the "dual hormone" hypothesis beyond testosterone. PMID:25765756

  12. Study on the impact of industrial flue gases on the PCDD/Fs congener profile in ambient air.

    PubMed

    Węgiel, Małgorzata; Chrząszcz, Ryszard; Maślanka, Anna; Grochowalski, Adam

    2014-11-01

    The aim of this study was to examine the impact of emissions from combustion processes from sinter, medical, waste and sewage waste incineration plants on the PCDD and PCDF congener profile in ambient air in Krakow (city in Poland). The subject matter of the study were air samples from the outskirts and the city center. It was found that in flue gases from industrial sources and in ambient air the share of PCDF congeners in relation to the total content of PCDD/Fs was higher than the share of PCDDs. However, in air samples collected in the city center, this relationship was reversed. The PCDD congener profiles in flue gases and in air samples are comparable. However, in the samples from the city centre, the share of OCDD is significantly higher and amounts to about 80%. The PCDF congener shares show higher spatial diversity, although in all the analyzed air samples, ODCF and 1,2,3,4,6,7,8 HpCDF dominated. Analyzing the share of congeners in regard to the sum of PCDDs/Fs a mutual resemblance of air from the suburbs, exhaust gases from the sinter ore and sewage sludge incinerator plant was observed. The study showed a similarity between the profile of congeners in air from the city centre and exhaust gases from the medical waste incinerator.

  13. Estradiol and its membrane-impermeable conjugate estradiol-BSA inhibit tamoxifen-stimulated prolactin secretion in incubated rat pituitaries.

    PubMed

    Aguilar, R; Bellido, C; Garrido-Gracia, J C; Alonso, R; Sánchez-Criado, J E

    2006-04-01

    In the absence of estrogen (E), the selective E receptor modulator tamoxifen (TX) has two agonist effects in the rat pituitary: induction of progesterone receptor (PR)-dependent GnRH self-priming in the gonadotrope, and stimulation of prolactin (PRL) secretion in the lactotrope. TX-induced gonadotropin (GnRH) self-priming is absent when 10(-8) M estradiol-17beta (E2) is added to the incubation medium of pituitaries from TX-treated rats. The present experiments investigated whether PR-independent PRL release into the incubation medium of pituitaries from TX-treated ovariectomized (OVX) rats was affected by E2, and the effect of different ER ligands (ICI182780, TX, estradiol-17alpha, E2 -BSA) on TX-stimulated PRL secretion. Moreover, the effect of E2 on TRH-stimulated PRL secretion in pituitaries collected from estradiol benzoate- and TX-treated OVX rats was studied. It was found that: i) incubation with E2 supressed the PRL releasing effect of injected TX; ii) whereas coincubation with the pure anti-E type II ICI182780 antagonized the inhibitory effect of E2, coincubation with the anti-E type I TX did not; iii) estradiol-17alpha lacked inhibitory action, whereas a dose-dependent inhibitory effect of both E2 and E2 -BSA was noticed; and iv) TRH stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked by addition of E2 to the medium. Taken together, these data argue in favor of the presence of specific membrane recognition sites for E in the lactotrope involved in steroid-specific E2 inhibition of TX-stimulated PRL secretion.

  14. Estradiol and its membrane-impermeable conjugate estradiol-BSA inhibit tamoxifen-stimulated prolactin secretion in incubated rat pituitaries.

    PubMed

    Aguilar, R; Bellido, C; Garrido-Gracia, J C; Alonso, R; Sánchez-Criado, J E

    2006-04-01

    In the absence of estrogen (E), the selective E receptor modulator tamoxifen (TX) has two agonist effects in the rat pituitary: induction of progesterone receptor (PR)-dependent GnRH self-priming in the gonadotrope, and stimulation of prolactin (PRL) secretion in the lactotrope. TX-induced gonadotropin (GnRH) self-priming is absent when 10(-8) M estradiol-17beta (E2) is added to the incubation medium of pituitaries from TX-treated rats. The present experiments investigated whether PR-independent PRL release into the incubation medium of pituitaries from TX-treated ovariectomized (OVX) rats was affected by E2, and the effect of different ER ligands (ICI182780, TX, estradiol-17alpha, E2 -BSA) on TX-stimulated PRL secretion. Moreover, the effect of E2 on TRH-stimulated PRL secretion in pituitaries collected from estradiol benzoate- and TX-treated OVX rats was studied. It was found that: i) incubation with E2 supressed the PRL releasing effect of injected TX; ii) whereas coincubation with the pure anti-E type II ICI182780 antagonized the inhibitory effect of E2, coincubation with the anti-E type I TX did not; iii) estradiol-17alpha lacked inhibitory action, whereas a dose-dependent inhibitory effect of both E2 and E2 -BSA was noticed; and iv) TRH stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked by addition of E2 to the medium. Taken together, these data argue in favor of the presence of specific membrane recognition sites for E in the lactotrope involved in steroid-specific E2 inhibition of TX-stimulated PRL secretion. PMID:16595727

  15. Accumulation of PCB congeners in nestling tree swallows (Tachycineta bicolor) on the Hudson River, New York

    USGS Publications Warehouse

    Echols, Kathy R.; Tillitt, Donald E.; Nichols, John W.; Secord, Anne L.; McCarty, John P.

    2004-01-01

    Tree swallows (Tachycineta bicolor) were used as a sentinel species to monitor the contamination and bioavailability of polychlorinated biphenyls (PCBs) in the Hudson River watershed. Several tree swallow nest box colonies around and downstream from Hudson Falls, NY, were studied. Tree swallow eggs, adults, and 5-, 10-, and 15-day-old nestlings were collected and analyzed for 103 PCB congeners. Emergent insects collected by net (primarily Odonata) or as a food bolus (primarily Diptera) taken from the mouths of adult tree swallows returning to the nest were analyzed in the same manner. Total PCB concentrations (wet weight) in eggs from two contaminated sites ranged from 9000 to 25 000 ng/g and accumulated to 32 000 and 96 000 ng/g in 15-day-old nestling at two contaminated sites. The congener patterns of PCBs in eggs, nestlings, and adults were compared to those found in emergent insects (Odonata and Diptera) using principal components analysis. The PCB patterns of the biota differed from that of Aroclor technical mixtures. PCB patterns in adult tree swallows were similar to those in eggs, while the patterns in dietary insects were similar to nestling tree swallows. Uptake rate constants were determined for tree swallow nestlings and compared between the two contaminated sites. The estimated PCB congener uptake rate constants were 0.008-0.02 d-1 based on uptake in nestlings until day 15 post-hatch. The rate constants were comparable between the two study areas and may be used to predict nestling contamination at other locations. Our studies confirm the utility of nestling tree swallows to evaluate localized PCB contamination.

  16. Genomic structure and genetic drift in C57BL/6 congenic metabolic mutant mice.

    PubMed

    Almodovar, Alvin J O; Luther, Rita J; Stonebrook, Caron L; Wood, Philip A

    2013-11-01

    We used a genome-wide single nucleotide polymorphism (SNP) approach to characterize the genomic structures of four representative C57BL/6 (B6) congenic mutant mouse lines to include the A) long-chain acyl-CoA dehydrogenase (Acadl), B) melanocortin 3 receptor (Mc3r), C) endothelial nitric oxide synthase (Nos3), and D) a replacement of mouse apolipoprotein E (Apoe) by human apolipoprotein E-2 (APOE2). We wanted to evaluate the size and flanking genes of the 129 strain origin mutant allele intervals on the B6 background. Additionally, we wanted to evaluate genetic drift among not only the four mutant lines and their respective B6 origin substrains, but also the drift between two commonly used B6 lines obtained from Jackson Laboratory and Taconic. Overall, we found a range of 129 origin interval sizes in the congenic mutant lines analyzed that ranged from a ~2.8 kb human sequence for APOE2 embedded in a 129S6 interval to the largest being a ~16 Mb fragment containing the targeted Nos3 (eNos) gene. Given the range of 129 strain interval sizes, we found 129 strain flanking genes via annotation in genome data bases ranging from one gene both upstream and downstream of the APOE2 allele to seven genes-upstream and five genes-downstream at the Nos3 locus. Furthermore, we found fourteen SNP differences between the Jackson Laboratory and Taconic B6 mice. These genetic differences were associated with marked adiposity differences between the two B6 substrains. This study demonstrates both the fidelity and the caveats of using congenic gene targeted mouse models and recognizing the importance of selecting the appropriately matched wild-type control mouse line.

  17. Acute toxicity of PCB congeners to Daphnia magma and Pimephales promelas

    SciTech Connect

    Dillon, T.M. ); Burton, W.D.S. )

    1991-02-01

    The acute toxicity (EC50/LC50) of commercial PCB mixtures has been reported to range from 2.0 to 283 ug/L. Because PCBs are very hydrophobic most biological studies have utilized a carrier solvent to facilitate introduction of PCBs into aqueous solution. As a result, biological effects are often reported at exposure concentrations exceeding water solubility. The purpose of this work was to evaluate the comparative toxicity of selected PCB congeners without carrier solvents. These tests were conducted on early life stages of two sensitive freshwater organisms, Daphnia magna and Pimephales promelas.

  18. A new Loewia Egger (Diptera: Tachinidae) from Turkey, with taxonomic and nomenclatural remarks on congeners.

    PubMed

    Cerretti, Pierfilippo; Lo Giudice, Giuseppe; O'Hara, James E

    2014-01-01

    The new species Loewia papei sp. nov. from southern Anatolia (Turkey) is described, illustrated and compared with congeners. A brief diagnosis of Loewia Egger is provided and the systematics of the genus are discussed. Loewia nudigena Mesnil, 1972 is fixed as the type species of Fortisia Rondani, 1861 (junior synonym of Loewia). A full list of previously known valid species of Loewia is provided along with information on primary types, type repositories (where known), and type localities. A lectotype is designated for Thrychogena brevifrons Rondani, 1856 (= Loewia brevifrons (Rondani, 1856)).

  19. A mass spectroscopic method for analysis of AHH-inducing and other polychlorinated biphenyl congeners and selected pesticides in fish

    USGS Publications Warehouse

    Schmidt, Larry J.; Hesselberg, Robert J.

    1992-01-01

    The 209 polychlorinated biphenyl (PCB) congeners exhibit a wide range in toxicity to fish, birds, and mammals. This paper discusses the use of gas chromatography/mass spectrometry negative chemical ionization (GC/MS-NCI) to quantify congeners of highly suspected toxicity such as IUPAC #77 (3,3',4,4'-tetrachlorobiphenyl) and #126 (3,3',4,4',5-pentachlorobiphenyl). GC/MS analysis time needed to produce the necessary resolution was reduced to 1 h per sample or standard, allowing an autosampler to inject 12 samples in 24 hours, plus 12 standards/QC samples. Identification and quantification of some 60+ congeners and several selected pesticides and estimation of total PCBs are also possible within the 1 h analysis. For congeners of high chlorination (penta through octa), the method exhibited excellent sensitivity, such that we could not locate a fish which exhibited PCB levels below our calibrated quantitation range. NCI was not as sensitive for mono through tri and for some tetrachlorinated PCB congeners, an exception being PCB #77, for which sensitivity was of the same order as for the more highly chlorinated biphenyls. Long term stability was excellent. Over a 6-mo period, results of replicate analyses for PCB congeners and pesticides in a composited sample of lake trout (Salvelinus namaycush) from Lake Michigan had a relative standard deviation of 12% of the mean. Over the same time period, mean recoveries for samples spiked at concentrations similar to those in Lake Michigan lake trout were 90-102%. Response was linear over a wide range of concentrations for each of the analyzed compounds. This method is now being used for routine analysis of PCB congeners and selected pesticides in our laboratory.

  20. The smallest available estradiol transdermal patch: a new treatment option for the prevention of postmenopausal osteoporosis.

    PubMed

    Bertonazzi, Abigail; Nelson, Bridgette; Salvador, Jamie; Umland, Elena

    2015-11-01

    Minivelle(®) (Noven Therapeutics, LLC, FL, USA) is an estradiol transdermal delivery system that has recently been approved in the USA for prevention of postmenopausal osteoporosis. The decline in estrogen during menopause leads to bone resorption, increasing the risk of fractures. Transdermal estradiol has been shown to increase bone mineral density. Safety studies of transdermal estradiol have shown a decreased risk in cardiovascular disease as compared with oral estrogen therapy. Minivelle is currently the smallest available transdermal estradiol patch, providing the lowest effective dose of estrogen.

  1. Estradiol facilitates the release of NPY to suppress hippocampus-dependent seizures

    PubMed Central

    Ledoux, Veronica A.; Smejkalova, Tereza; May, Renee M.; Cooke, Bradley M.; Woolley, Catherine S.

    2009-01-01

    About one-third of women with epilepsy have a catamenial seizure pattern, in which seizures fluctuate with the menstrual cycle. Catamenial seizures occur more frequently when the ratio of circulating estradiol to progesterone is high, suggesting that estradiol is proconvulsant. We used adult female rats to test how estradiol-induced suppression of GABAergic inhibition in the hippocampus affects behavioral seizures induced by kainic acid. As expected, estradiol decreased the latency to initiate seizures, indicating increased seizure susceptibility. At the same time, however, estradiol also shortened the duration of late-stage seizures, indicating decreased seizure severity. Further analyses showed that the decrease in seizure severity was due to greater release of the anticonvulsant neuropeptide, neuropeptide Y (NPY). First, blocking hippocampal NPY during seizures eliminated the estradiol-induced decrease in seizure duration. Second, light and electron microscopic studies indicated that estradiol increases the potentially releasable pool of NPY in inhibitory presynaptic boutons and facilitates the release of NPY from inhibitory boutons during seizures. Finally, the presence of estrogen receptor-α on large dense core vesicles (LDCVs) in the hippocampus suggests that estradiol could facilitate neuropeptide release by acting directly on LDCVs themselves. Understanding how estradiol regulates NPY-containing LDCVs could point to molecular targets for novel anticonvulsant therapies. PMID:19193892

  2. Estradiol and Progesterone have Opposing Roles in the Regulation of Fear Extinction in Female Rats.

    PubMed

    Graham, Bronwyn M; Daher, Melissa

    2016-02-01

    Fear extinction, the laboratory basis of exposure therapy for anxiety disorders, fluctuates across the female rat estrous cycle, where extinction is enhanced during proestrus (high estradiol and progesterone), and impaired during metestrus (low estradiol and progesterone). During the estrous cycle increasing levels of estradiol precede and then overlap with increased levels of progesterone. We sought to isolate the impact of these hormonal changes on fear extinction by systematically treating ovariectomized female rats with estradiol alone, or in combination with progesterone. We found that estradiol alone facilitated extinction recall, whereas the effects of progesterone on estradiol-treated rats were biphasic and dependent on the time interval between progesterone administration and extinction training. Progesterone potentiated estradiol's facilitation of extinction recall when extinction training occurred 6 h after progesterone administration. However, progesterone abolished estradiol's facilitation of extinction recall when extinction training occurred 24 h after progesterone administration. Furthermore, in naturally cycling rats, blocking progesterone receptor activation during proestrus (when progesterone levels peak) prevented the impairment in extinction recall in rats extinguished during metestrus. These results suggest that in naturally cycling females whereas cyclical increases in estradiol facilitate fear extinction, cyclical increases in progesterone may lead to fear extinction impairments. As extinction training took place after the hormonal treatments had been metabolized, we propose that genomic mechanisms may at least partly mediate the impact of cyclic fluctuations in sex hormones on fear extinction.

  3. TEMPORAL AND CONCENTRATION DEPENDENT ESTRADIOL EFFECTS ON NEURAL PATHWAYS MEDIATING SEXUAL RECEPTIVITY

    PubMed Central

    Micevych, Paul; Sinchak, Kevin

    2013-01-01

    The acceptance of estradiol signaling through receptors found in the cell membrane, as well as, the nucleus has provided for a re-examination of timing and location of estradiol actions on neural circuits mediating sexual receptivity (lordosis). Estradiol membrane signaling involves the transactivation of metabotropic glutamate receptors (mGluR) that transduce steroid information through PKC signaling cascades producing rapid activation of lordosis regulating circuits. It has been known for some time that estradiol initially produces an inhibition of the medial preoptic nucleus (MPN). We have demonstrated that underlying this inhibition is estradiol acting in the arcuate nucleus to induce β-endorphin release which inhibits the MPN through a μ-opioid receptor mechanism. This transient inhibition is relieved by either subsequent progesterone treatment or longer exposure to higher doses of estradiol to facilitate lordosis behavior. We review recent findings about estradiol membrane signaling inducing dendritic spine formation in the arcuate nucleus that is critical for estradiol induction of sexual receptivity. Moreover, we discuss the evidence that in addition to ERα, several other putative membrane estrogen receptors facilitate lordosis behavior through regulation of the arcuate nucleus. These include the GRP30 and the STX activated Gq-mER. Finally, we report on the importance of GABA acting at GABAB receptors for estradiol membrane signaling that regulates lordosis circuit activation and sexual receptivity. PMID:24028299

  4. A Comparison of the Effects of Transdermal Estradiol and Estradiol Valerate on Endometrial Receptivity in Frozen-thawed Embryo Transfer Cycles: A Randomized Clinical Trial

    PubMed Central

    Davar, Robab; Janati, Sima; Mohseni, Fereshteh; Khabazkhoob, Mehdi; Asgari, Soheila

    2016-01-01

    Background: The purpose of this study was to determine the optimal endometrial preparation protocol by comparing the clinical outcome of two methods of endometrial preparation in frozen-thawed embryo transfer (FET) cycles, including that is, oral estradiol and 17ß-estradiol transdermal patch. Methods: In this randomized controlled trial, women underwent either conventional IVF or intracytoplasmic sperm injection (ICSI) who had at least two top-quality embryos appropriate for cryopreservation and frozen embryos from previous cycles. In the study group (n=45), 17-B estradiol transdermal patches 100 μg were applied from the second day of the cycle and continued every other day. Then, each patch was removed after four days. In the control group (n=45), oral estradiol valerate 6 mg was started at the same time and continued daily. Results: There was a significant difference in estradiol level on the day of progesterone administration and the day of embryo transfer between the two groups (p= 0.001 in both), but no significant difference was observed between them in biochemical and clinical pregnancy rates (32.6% vs. 33.3%, p=1.000 and 30.2% vs. 33.3%, p=0.810, respectively). Conclusion: It is suggested that estradiol transdermal patches be used instead of oral estradiol in FET cycles. Due to the reduced costs, drug dose, and emotional stress as well as the simplicity of the protocol for patients. PMID:27141464

  5. [Indoor deposition flux and congener profiles of polybrominated diphenyl ethers (PBDEs) in Shanghai, China].

    PubMed

    Han, Wen-liang; Feng, Jia-liang; Peng, Xiao-xia; Wu, Ming-hong; Fu, Jia-mo

    2010-03-01

    Indoor dry deposition of eight homes and offices in the urban area of Shanghai, China were sampled with clean glass plate during July to August of 2008 to study the indoor deposition flux and congener profiles of polybrominated diphenyl ethers (PBDEs). 16 PBDEs congeners which including BDE-17, -28, -71, 47, -66, -77, -100, -99, -85, -118, -154, -153, -138, -183, -190 and BDE-209 were measured by GC-MS with negative chemical ionization (NCI) in selected ion monitoring (SIM) mode. The particulate deposition flux of PBDEs in homes and offices were (10.9 +/- 8.2) and (14.2 +/- 11.9) ng x (m2 x d)(-1) respectively. Deca-BDE (BDE-209) was the major compound, accounting for 88.2% -99.2% of the quantified PBDEs. The particulate deposition flux in the offices [(3.1 +/- 2.0) mg x (m2 x d)(-1)] was relatively lower than that of homes, but the concentration of PBDEs in the particles [(3361.6 +/- 1987.4) ng x g(-1)] was significantly higher than that of homes [(1169.1 +/- 647.1) ng x g(-1)]. The concentration of PBDEs in the indoor dry deposition of Shanghai ranked in the middle level comparing with other cities around the world. The indoor deposition flux of PBDEs was mainly correlated with the flux of particle deposition and the usage of electrical and electronic products, but not the interior decoration and the amount of furniture.

  6. Levels and congener profiles of PBDEs in edible Baltic, freshwater, and farmed fish in Finland.

    PubMed

    Airaksinen, Riikka; Hallikainen, Anja; Rantakokko, Panu; Ruokojärvi, Päivi; Vuorinen, Pekka J; Mannio, Jaakko; Kiviranta, Hannu

    2015-03-17

    Fish is the major source of polybrominated diphenyl ethers (PBDEs) for Finnish consumers. To estimate the PBDE contamination in fish that Finns regularly consume as food, a large-scale sampling was undertaken in 2009-2010. Altogether 207 samples of 17 edible fish species were collected from commercially and recreationally important fishing areas in the Baltic Sea, freshwater lakes, and farming facilities. The analysis of 15 PBDE congeners was performed in an accredited testing laboratory with high-resolution gas chromatography mass spectrometry. In all of the samples, the Σ15PBDE varied between 0.029 and 73 ng/g fw. The most abundant congeners were BDE-47 (average proportion 42%), -99 (8.4%), -100 (11%), -154 (5.6%), and -209 (27%). High levels of BDE-209 were observed in the Baltic Sea, off the coast of Pori, in Baltic herring, perch, pike, and pike-perch. Overall, the PBDE levels in Baltic and freshwater fish were low. The levels in farmed whitefish were slightly higher than in wild whitefish. The reasons for the high BDE-209 levels in Baltic herring in Pori and the elevated levels of PBDEs in farmed whitefish should be investigated more thoroughly.

  7. SAR of Sponge-Inspired Hemibastadin Congeners Inhibiting Blue Mussel PhenolOxidase

    PubMed Central

    Niemann, Hendrik; Hagenow, Jens; Chung, Mi-Young; Hellio, Claire; Weber, Horst; Proksch, Peter

    2015-01-01

    Hemibastadin derivatives, including the synthetically-derived 5,5′-dibromohemibastadin-1 (DBHB), are potent inhibitors of blue mussel phenoloxidase (PO), which is a key enzyme involved in the firm attachment of this invertebrate to substrates and, thus, a promising molecular target for anti-fouling research. For a systematic investigation of the enzyme inhibitory activity of hemibastadin derivatives, we have synthesized nine new congeners, which feature structural variations of the DBHB core structure. These structural modifications include, e.g., different halogen substituents present at the aromatic rings, different amine moieties linked to the (E)-2-(hydroxyimino)-3-(4-hydroxyphenyl)propionic acid, the presence of free vs. substituted aromatic hydroxyl groups and a free vs. methylated oxime group. All compounds were tested for their inhibitory activity towards the target enzyme in vitro, and IC50 values were calculated. Derivatives, which structurally closely resemble sponge-derived hemibastadins, revealed superior enzyme inhibitory properties vs. congeners featuring structural moieties that are absent in the respective natural products. This study suggests that natural selection has yielded structurally-optimized antifouling compounds. PMID:25988522

  8. Linking habitat use of Hudson River striped bass to accumulation of polychlorinated biphenyl congeners

    SciTech Connect

    Ashley, J.T.F.; Secor, D.H.; Zlokovitz, E.; Wales, S.Q.; Baker, J.E.

    2000-03-15

    Since 1976, the commercial striped bass fishery in the Hudson River (NY) has been closed due to total polychlorinated biphenyl (t-PCB) concentrations that exceed the US Food and Drug Administration's advisory level of 2 {micro}g/g-wet weight. Extensive monitoring of Hudson River striped bass demonstrated much more variability in t-PCB levels among individual striped bass than could be explained by their age, sex, or lipid contents. To investigate the possible role of differential habitat use among subpopulations of striped bass in controlling their PCB exposures, 70 fish collected throughout the Hudson River estuary and Long Island Sound in 1994--1995 were analyzed for PCB congeners, and their lifetime migration behaviors were estimated by otolith microchemistry. The mean salinity encountered during the fish's last growth season prior to capture was inversely correlated with the t-PCB body burden. Striped bass permanently residing in fresh and oligohaline portions of the estuary adjacent to known PCB sources had elevated t-PCB levels and congeneric patterns with higher proportions of di-, tri-, and tetrachlorobiphenyls. Conversely, fish spending the majority of their life in more saline waters of the estuary or migrating frequently throughout the salinity gradient contained lower PCB levels composed of more highly chlorinated congeners. The approach used in this study allows habitat use to be incorporated into exposure assessments for anadromous fish species such as striped bass.

  9. Breeding and preliminarily phenotyping of a congenic mouse model with alopecia areata

    PubMed Central

    GU, Mei-Er; SONG, Xiao-Ming; ZHU, Chun-Feng; YIN, Hong-Ping; LIU, Gui-Jie; YU, Li-Ping; YANG, Wei-Wei; NI, Li-Feng; ZHANG, Yan-Li; WU, Bao-Jin

    2014-01-01

    In the current study, the alopecia areata gene was introduced into the C57BL/6 (B6) mouse through repeated backcrossing/intercrossing, and the allelic homozygosity of congenic AAtjmice (named B6.KM-AA) was verified using microsatellites. The gross appearance, growth characteristics, pathological changes in skin, and major organs of B6.KM-AA mice were observed. Counts and proportions of CD4+ and CD8+ T lymphocytes in peripheral blood were determined by flow cytometry. Results show that congenic B6.KM-AA mice were obtained after 10 generations of backcrossing/intercrossing. B6.KM-AA mice grew slower than B6 control mice and AA skin lesions were developed by four weeks of age. The number of hair follicles was reduced, but hair structures were normal. Loss of hair during disease progression was associated with CD4+ and CD8+ T lymphocytes infiltration peri- and intra- hair follicles. No pathological changes were found in other organs except for the skin. In the peripheral blood of B6.KM-AA mice, the percentage of CD4+ T cells was lower and percentage of CD8+ T cells higher than in control mice. These findings indicate that B6.KM-AA mice are characterized by a dysfunctional immune system, retarded development and T-cell infiltration mediated hair loss, making them a promising new animal model for human alopecia areata. PMID:25017742

  10. Enhanced accumulation of PCB congeners by Baltic Sea blue mussels, Mytilus edulis, with increased algae enrichment

    SciTech Connect

    Gilek, M.; Bjoerk, M.; Broman, D.; Kautsky, N.; Naef, C.

    1996-09-01

    The objective of this study was to examine if natural variations in the quantity of phytoplankton-derived particulate and dissolved organic carbon influences the accumulation of polychlorinated biphenyls (PCBs) in the tissues of Baltic Sea blue mussels (Mytilus edulis L.). In a laboratory flow-through experiment the authors exposed M. edulis to the technical PCB mixture Aroclor{reg_sign} 1248 for 21 d at three different enrichments of the unicellular green algae Chlamydomonas sp., 0.10, 0.16, and 0.32 mg particulate organic carbon (POC)/L. Tissue and water concentrations were determined for seven PCB congeners and 21-d bioaccumulation factors were calculated against total water concentrations. Contrary to what would be expected, an increase in algae enrichment from 0.10 to 0.32 mg POC/L resulted in an enhanced PCB accumulation by a factor of approx. 2. This increase in PCB accumulation was more pronounced for PCB congeners with lower hydrophobicity. These observations have implications for the design of laboratory accumulation studies and potentially for PCB accumulation and cycling in field populations of suspension-feeding mussels in response to changes in eutrophication status.

  11. Distribution of PCB congeners in seven lake systems: Interactions between sediment and food-web transport

    SciTech Connect

    MacDonald, C.R.; Metcalfe, C.D.; Balch, G.C.; Metcalfe, T.L. . Environmental and Resource Studies)

    1993-11-01

    A study was conducted to examine the role of two processes, partitioning of PCBs between sediment and biota and food-web transport, in determining the concentration of PCB congeners in the biota of seven lakes. Biota PCB concentration (lipid)-to-sediment PCB concentration (organic carbon), or BSF, ratios were calculated as markers of the partitioning of PCBs between biota and sediment, and biota PCB concentration (lipid)-to-zooplankton PCB concentration (lipid), or BAS, ratios were calculated as markers of the transport of PCBs through food webs. The lakes ranged from a shallow, well-mixed lake with a historic input of Aroclor technical mixtures to deeper, oligotrophic systems in which atmospheric deposition was the only known source. BSF ratios ranged from approximately one in cyprinids and zooplankton in all lakes to 30 in yellow perch in one lake. A significant correlation between lake maximum depth and combined BSF ratios for all biota indicated that PCBs were generally more available for accumulation in the shallower lakes, regardless of the PCB source. Principal component analysis (PCA) showed that the biota in the shallower lakes had higher ratios of higher chlorinated congeners, suggesting that predictions of equal concentrations of hydrophobic contaminants on a lipid basis in sediment and lower trophic levels may significantly underestimate the accumulation of very hydrophobic compounds in the organisms of some lake systems. BAF ratios ranged from approximately one in the lower trophic levels to approximately 10 in lake trout.

  12. Toxic cell concentrations of three polychlorinated biphenyl congeners in the green alga, Selenastrum capricornutum

    SciTech Connect

    Mayer, P. |; Halling-Soerensen, B.; Nyholm, N.; Sijm, D.T.H.M.

    1998-09-01

    Algal growth inhibition tests were performed with the unicellular green alga Selenastrum capricornutum and three {sup 14}C-labeled polychlorinated biphenyl (PCB) congeners. Toxicity was related to external aqueous concentrations and additionally to internal algal bound PCB concentrations. Estimates of the concentrations at 50% effectiveness (EC50s) for the three PCB congeners ranged within a factor of 17 when based on measured aqueous concentrations. When based on internal toxicant concentrations the corresponding range was 6.7 to 14.3 mmol/kg wet weight. Thus, changing the basis from external to internal concentrations reduced the range by almost one order of magnitude. Additional toxic cell concentrations of five monoaromatic compounds and S. capricornutum were calculated from literature data to be in the same order of magnitude as the experimental toxic cell concentrations for the PCBs, whereas EC50 values for all substances ranged by more than four orders of magnitude. The experimental and calculated data indicate that observed differences in the estimated EC50 values were mainly due to differences in bioconcentration behavior rather than to different intrinsic toxicities. These findings are in agreement with the concept of baseline toxicity, meaning that a number of hydrophobic organics exerts their acute toxicity by one relatively nonspecific mode of action.

  13. Polychlorinated biphenyls in Great Lakes lake trout and their eggs: relations to survival and congener composition 1979-1988

    USGS Publications Warehouse

    Mac, Michael J.; Schwartz, Ted R.; Edsall, Carol C.; Frank, Anthony M.

    1993-01-01

    Eggs taken from lake trout (Salvelinus namaycush) captured from various Great Lakes between 1979 and 1988 were analyzed for individual polychlorinated biphenyl (PCB) congeners. Eggs from the same fish had been previously reared through hatching and early fry development to ascertain egg quality. Tissues from a subsample of the adult females that provided eggs were similarly analyzed. Significant relations were found between embryonic mortality (eggs dying between fertilization and hatch) and the concentrations of total PCBs in both the eggs and adults. PCB concentrations were also negatively correlated with the percentage of normal fry that successfully hatched, but no relation was found between PCB residues and fry mortality. Pattern recognition analysis indicated that the PCB congener fingerprint for eggs from Lake Superior was different than that of eggs from Lakes Michigan, Huron, and Ontario. A difference between PCB residue patterns was also identified between eggs and the parent fish. While this difference indicated some preferential deposition of congeners in the eggs, the difference was not attributed to the toxic AHH-active congeners. No difference in the PCB pattern was observed over the 10 years of sample collection, demonstrating that concentrations of individual congeners are declining at similar rates.

  14. PCB congener patterns in rats consuming diets containing Great Lakes salmon: Analysis of fish, diets, and adipose tissue

    SciTech Connect

    Jordan, S.A.; Feeley, M.M.

    1999-02-01

    As part of a multidisciplinary toxicological investigation into Great Lakes contaminants, chinook salmon were collected from lake Huron (LH) and Lake Ontario (LO) and incorporated into standard rat diets as 20 or 100% of the protein complement. Final PCB concentrations in the experiment ranged from 3.15 ng/g in the control diet to 1,080 ngg in the high-dose LO diet, with maximal estimated daily consumption by the rats of 82 {micro}g PCBs/kg body wt in the LO20 dietary group. Seventeen PCB congeners, PCB 85, 99, 101, 105, 110, 118, 128, 129, 132, 138, 149, 153, 170, 177, 180, 187, and 199, occurred at > 3.0% of the total PCBs in the fish with no major site differences. Cumulatively, these 17 congeners accounted for up to 75% of the total PCBs in the fish compared to 44 and 54% in two commercial Aroclors, 1254 and 1260, respectively. PCB 77 was the major dioxin-like congener in the fish, followed by PCB 126 and then PCB 169. All major dietary congeners bioaccumulated in the adipose tissue of the rats with the exception of PCB congeners 101, 110, 132, and 149.

  15. Protein Restriction during Pregnancy Induces Hypertension in Adult Female Rat Offspring—Influence of Estradiol

    PubMed Central

    Sathishkumar, K; Elkins, Rebekah; Yallampalli, Uma; Yallampalli, Chandra

    2011-01-01

    We previously reported that gestational dietary protein restriction in rats causes gender-related differences in development of offspring's blood pressure (BP) that is more pronounced in the males than females. Since such effects may depend on sex hormones, we investigated the role of estradiol in the development of hypertension in female offspring of protein restricted dams. Female offspring of pregnant rats fed normal (20%) or protein restricted (6%) casein diets throughout pregnancy were kept either, intact, ovariectomized or ovariectomized with estradiol supplementation. BP, estradiol and testosterone levels and vascular estrogen receptor (ER) were examined. BP was significantly higher and plasma estradiol levels were significantly lower by 34% in intact protein restricted female offspring compared to corresponding controls. Further decrease in estradiol levels by ovariectomy exacerbated hypertension in the protein restricted females with an earlier onset and more prominent elevation in BP compared to controls. Estradiol supplementation in ovariectomized protein restricted females significantly reversed ovariectomy-induced hypertension but did not normalize BP to control levels. The hypertensive protein restricted females have reduced vascular ERα expression that was unaffected by ovariectomy or estradiol replacement. In addition, the testosterone levels were significantly higher by 2.4-, 3.4-, and 2.8-fold in intact, ovariectomized and estradiol replaced protein restricted females compared to corresponding controls. Our data show that: 1) hypertension in protein restricted adult female offspring is associated with reduced plasma estradiol levels, 2) estradiol protects and limits the severity of hypertension in protein restricted females and contribute for sexual dimorphism, and 3) Estradiol replacement fails to completely reverse hypertension, which may be related to limited availability of vascular ERα receptors and/or increased circulating testosterone

  16. Sampling the Hudson River estuary for PCBs using multiplate artificial substrate samplers and congener-specific gas chromatography in 1991

    SciTech Connect

    Bush, B. . Wadsworth Center for Labs. and Research State Univ. of New York, Albany, NY . School of Public Health); Dzurica, S. . School of Public Health); Wood, L.; Madrigal, E.C. . Wadsworth Center for Labs. and Research)

    1994-08-01

    During the summer of 1991, multiplate artificial substrate samplers were deployed at five locations in the Hudson River from Troy to Poughkeepsie, New York. The sedimentary material that collected on these plates was fractionated and analyzed using a congener-specific method for PCB content. The results were compared intrasite, intersite, and across time. The authors found no difference between the PCB congener distribution patterns in the coarse and fine fractions, as determined by linear regression. They also found little evidence of intersite differentiation--they found no discernible difference in PCB congener distribution, but they did find a difference in magnitude. The 1991 results were then compared to the results from a previous study conducted from 1977 to 1985. They found that over the studied 120 km stretch of the river there has been a 3.7 [+-] 1.2% per annum decline in PCB multiplate residue since 1983.

  17. Biochemical properties and binding parameters of the pancreatic estradiol binder.

    PubMed

    Drury, R E; Sandberg, A A

    1987-01-01

    Because the estradiol binder is distributed throughout subcellular fractions from homogenates of the pancreas, an acetone powder was used in extracting soluble components from the entire tissue. The estradiol binder, obtained from the acetone powder of a bovine pancreas, was pH dependent, denatured by heat, inhibited by CuSO4 and reversibly denatured by urea. Binding was enhanced by Mg+2, a common enzymatic cofactor. Its molecular weight was greater than 66,000 D, the molecular weight of bovine serum albumin. An 11-fold purification resulted in a protein preparation that showed a saturating binding curve in equilibrium dialysis. Klotz has severely criticized, if not discredited, the hypothesis that a binding curve is typically due to two classical binding sites and is resolvable into two straight lines. We, therefore, determined the parameters of the binding curve by a computer analysis based on Wilkinson's algebraic method and on McLaren's proposal of surface relationships in enzymatic reactions. The inference from McLaren (namely, binding sites of a single affinity located on the surface of the macromolecular binder), offered a simpler explanation for curvature in Scatchard plots than the two affinity site or the varying affinity hypotheses. The analysis was also applied to other examples from the literature. PMID:3118355

  18. Estradiol increases salt intake in female normotensive and hypertensive rats.

    PubMed

    Kensicki, Eric; Dunphy, Gail; Ely, Daniel

    2002-08-01

    The objective of this study was to examine whether or not estradiol (E2) alters sodium intake in hypertensive and normotensive female rats. It was hypothesized that higher doses of E2 would increase sodium consumption and that this response would be greater in spontaneously hypertensive rats (SHR) compared with Wistar Kyoto (WKY) rats. The study involved female SHR and WKY (n = 12/group). All animals were ovariectomized. Six of twelve rats from each strain received three progressively larger doses of beta-estradiol propionate (each dose lasting 2 wk), whereas the other six rats from each strain received sham implants. Blood E2 levels were measured by radioimmunoassay after each 2-wk period, allowing a 10-day washout period before the next E2 dose. Rats had access to 0.0, 0.5, 1.0, and 1.5% NaCl solutions to drink throughout the experiment. There was a significant positive correlation between sodium intake and plasma E2 (r = 0.8, P < 0.001). Both strains avoided the 1.5% NaCl, and the increased sodium intake was achieved by an increase in consumption of the 0.5% NaCl. SHR females consumed more sodium than WKY females, which is similar to what has been observed in males of these strains. In conclusion, E2 was positively correlated with sodium intake in both strains of rat, with the hypertensive rats consuming more sodium than the normotensive rats.

  19. Ultrasound and estradiol plasma levels in threatened abortion.

    PubMed

    Melis, G B; Strigini, F; Fruzzetti, F; Paoletti, A M; Battistelli, P; Boldrini, A

    1984-01-01

    Ultrasound examination and unconjugated estriol assay were performed in 111 women with threatened abortion between the 6th and the 20th week of pregnancy. In viable pregnancies, fetal echoes and fetal heart movements were always observed by sonar from the 10th week onward and estradiol levels always increased above 30 pg/ml from the 13th week. Both ultrasound and estriol assay showed high percentages of uncertain prognostic indication on pregnancy outcome when examinations were performed during the first weeks of pregnancy. However, in the same period estriol levels higher than 30 pg/ml were always correlated with the favourable outcome of pregnancy, since no abortion occurred in subjects with detectable estriol values. During the second trimester ultrasound and estradiol results were normal in all viable pregnancies, while they were abnormal in 71.4% of pregnancies which failed to continue. Estriol values were always undetectable when fetuses could not be identified by sonar or they were dead. These data seem to demonstrate that both methods have similar prognostic value in patients with threatened abortion. However both sonar examination and estriol levels sometimes failed in predicting subsequent pregnancy interruptions, suggesting that abortions were not related to either fetal or placental alterations.

  20. 17β-Estradiol administration promotes delayed cutaneous wound healing in 40-week ovariectomised female mice.

    PubMed

    Mukai, Kanae; Nakajima, Yukari; Urai, Tamae; Komatsu, Emi; Nasruddin; Sugama, Junko; Nakatani, Toshio

    2016-10-01

    This study investigated the effect of 17β-estradiol on wound healing in 40-week ovariectomised female mice. Thirty-six-week-old female mice were divided into three groups: medication with 17β-estradiol after ovariectomy (OVX + 17β-estradiol), ovariectomy (OVX) and sham (SHAM). The mice received two full-thickness wounds, and the OVX + 17β-estradiol group was administered 17β-estradiol at 0·01 g/day until healing. In the OVX + 17β-estradiol group, the ratio of wound area was significantly smaller than those of the OVX and SHAM groups on days 1-3, 5, 6, 8-12 and 9-12, respectively, the numbers of neutrophils and macrophages were significantly smaller than those on days 3 and 7, the ratio of re-epithelialisation was significantly higher than those on days 3 and 11, the ratio of myofibroblasts was significantly higher than those on day 11 and smaller on day 14, and the ratio of collagen fibres was significantly larger than that of the OVX group on days 7-14. We found that 17β-estradiol administration promotes cutaneous wound healing in 40-week female mice by reducing wound area, shortening inflammatory response, and promoting re-epithelialisation, collagen deposition and wound contraction. Our results suggest that cutaneous wound healing that is delayed because of ageing is promoted by exogenous and continuous 17β-estradiol administration.

  1. THE PATHOBIOLOGY OF 17B-ESTRADIOL IN SUMMER FLOUNDER, PARALICHTYS DENTATUS

    EPA Science Inventory

    Estradiol has been shown to cause increased vitellogenin (VtG) concentrations in male fish. The intent of this study was to evaluate the pathobiology associated with exposure to 17 -estradiol (E2) on liver, gonad, and kidney tissues of summer flounder, Paralichthys dentatus. Juve...

  2. Effects of preovulatory estradiol concentration on embryo survival and pregnancy establishment in beef cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The role of estradiol during the preovulatory period on embryo survival and pregnancy establishment has not been characterized in beef cows. We hypothesized that preovulatory estradiol is important for embryo survival and pregnancy establishment in beef cows. In order to establish the importance o...

  3. Exogenous estradiol alters gonadal growth and timing of temperature sex determination in gonads of sea turtle.

    PubMed

    Díaz-Hernández, Verónica; Marmolejo-Valencia, Alejandro; Merchant-Larios, Horacio

    2015-12-01

    Temperature sex determining species offer a model for investigating how environmental cues become integrated to the regulation of patterning genes and growth, among bipotential gonads. Manipulation of steroid hormones has revealed the important role of aromatase in the regulation of the estrogen levels involved in temperature-dependent sex determination. Estradiol treatment counteracts the effect of male-promoting temperature, but the resulting ovarian developmental pattern differs from that manifested with the female-promoting temperature. Hypoplastic gonads have been reported among estradiol-treated turtles; however the estradiol effect on gonadal size has not been examined. Here we focused on the sea turtle Lepidochelys olivacea, which develops hypoplastic gonads with estradiol treatment. We studied the effect of estradiol on cell proliferation and on candidate genes involved in ovarian pattern. We found this effect is organ specific, causing a dramatic reduction in gonadal cell proliferation during the temperature-sensitive period. Although the incipient gonads resembled tiny ovaries, remodeling of the medullary cords and down-regulation of testicular factor Sox9 were considerably delayed. Contrastingly, with ovarian promoting temperature as a cue, exogenous estradiol induced the up-regulation of the ovary factor FoxL2, prior to the expression of aromatase. The strong expression of estrogen receptor alpha at the time of treatment suggests that it mediates estradiol effects. Overall results indicate that estradiol levels required for gonadal growth and to establish the female genetic network are delicately regulated by temperature.

  4. Exogenous estradiol alters gonadal growth and timing of temperature sex determination in gonads of sea turtle.

    PubMed

    Díaz-Hernández, Verónica; Marmolejo-Valencia, Alejandro; Merchant-Larios, Horacio

    2015-12-01

    Temperature sex determining species offer a model for investigating how environmental cues become integrated to the regulation of patterning genes and growth, among bipotential gonads. Manipulation of steroid hormones has revealed the important role of aromatase in the regulation of the estrogen levels involved in temperature-dependent sex determination. Estradiol treatment counteracts the effect of male-promoting temperature, but the resulting ovarian developmental pattern differs from that manifested with the female-promoting temperature. Hypoplastic gonads have been reported among estradiol-treated turtles; however the estradiol effect on gonadal size has not been examined. Here we focused on the sea turtle Lepidochelys olivacea, which develops hypoplastic gonads with estradiol treatment. We studied the effect of estradiol on cell proliferation and on candidate genes involved in ovarian pattern. We found this effect is organ specific, causing a dramatic reduction in gonadal cell proliferation during the temperature-sensitive period. Although the incipient gonads resembled tiny ovaries, remodeling of the medullary cords and down-regulation of testicular factor Sox9 were considerably delayed. Contrastingly, with ovarian promoting temperature as a cue, exogenous estradiol induced the up-regulation of the ovary factor FoxL2, prior to the expression of aromatase. The strong expression of estrogen receptor alpha at the time of treatment suggests that it mediates estradiol effects. Overall results indicate that estradiol levels required for gonadal growth and to establish the female genetic network are delicately regulated by temperature. PMID:26465360

  5. Luteinizing hormone secretion as influenced by age and estradiol in the prepubertal gilt

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of this study was to determine if there is an age related reduction in the sensitivity of the negative feedback action of estradiol on luteinizing hormone (LH) secretion in the prepubertal gilt. Ovariectomized gilts at 90 (n = 12), 150 (n = 11) or 210 (n = 12) days of age received estradiol ...

  6. Congener Patterns of Persistent Organic Pollutants Establish the Extent of Contaminant Biotransport by Pacific Salmon in the Great Lakes.

    PubMed

    Gerig, Brandon S; Chaloner, Dominic T; Janetski, David J; Rediske, Richard R; O'Keefe, James P; Moerke, Ashley H; Lamberti, Gary A

    2016-01-19

    In the Great Lakes, introduced Pacific salmon (Oncorhynchus spp.) can transport persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), to new environments during their spawning migrations. To explore the nature and extent of POP biotransport by salmon, we compared 58 PCB and 6 PBDE congeners found in spawning salmon directly to those in resident stream fish. We hypothesized that stream fish exposed to salmon spawners would have congener patterns similar to those of salmon, the presumed contaminant source. Using permutational multivariate analysis of variance (PERMANOVA) and nonmetric multidimensional scaling (NMDS), we found that POP congener patterns of Pacific salmon varied among regions in the Great Lakes basin (i.e., Lake Huron, Lake Michigan, or Lake Superior), tissue type (whole fish or eggs), and contaminant type (PCB or PBDE). For stream-resident fish, POP congener pattern was influenced by the presence of salmon, location (i.e., Great Lakes Basin), and species identity (i.e., brook trout [Salvelinus fontinalis] or mottled sculpin [Cottus bairdii]). Similarity in congener patterns indicated that salmon are a source of POPs to brook trout in stream reaches receiving salmon spawners from Lake Michigan and Lake Huron but not from Lake Superior. Congener patterns of mottled sculpin differed from those of brook trout and salmon, suggesting that brook trout and mottled sculpin either use salmon tissue to differing degrees, acquire POPs from different dietary sources, or bioaccumulate or metabolize POPs differently. Overall, our analyses identified the important role of salmon in contaminant biotransport but also demonstrated that the extent of salmon-mediated POP transfer and uptake in Great Lakes tributaries is location- and species-specific.

  7. A long-term study of anaerobic dechlorination of PCB congeners by sediment microorganisms pathways and mass balance

    SciTech Connect

    Rhee, G.Y.; Sokol, R.C.; Bush, B. . Wadsworth Center for Labs. and Research); Bethoney, C.M. . School of Public Health, New York State Dept. of Health)

    1993-10-01

    Reductive dechlorination of PCBs by Hudson River sediment microorganisms was investigated using individual congeners, 2,3,4,2[prime],4[prime],5[prime]-, 2,4,5,2[prime],4[prime],5[prime]-, 2,3,4,5,6-, 2,4,2[prime],4[prime]-, and 3,4,3[prime],4[prime]-chlorobiphenyls (CBPs) in long-term studies lasting 15 to 20 months. The dechlorination of 2,3,4,2[prime],4[prime],5[prime]-CBP yielded 2,4,5,2[prime],4[prime]-, 2,4,2[prime],4[prime]-, 2,4,2[prime],5[prime]-, and 2,4,2[prime],5[prime]-, and 2,4,2[prime]-CBPs; notably absent was 2,2[prime]-CBP. Yet, the total molar concentration of all congeners decreased with time and at 15 months accounted for only 25% of the initial concentration of the parent compound. 2,3,4,5,6-CBP produced 2,3,5,6-, 2,4,6-, and 2,6-CBPs. At 15 months the sum of all congeners accounted for only about 50% of the initial amount of the parent congener. On the other hand, 2,4,5,2[prime],4[prime],5[prime]-CBP yielded six daughter products, including 2,2[prime]-CBP, and did not show any decrease in total molar concentration even at 20 months. 2,4,2[prime],4[prime]-CBP did not show any change at 15 months. These results indicate that anaerobic PCB biotransformation may include mechanisms other than dechlorination and that the mechanisms are congener dependent. Biphenyl was detected with 3,4,3[prime],4[prime]-CBP, indicating complete dechlorination; however, it accounted for <10% of the total molar loss. [sup 14]C-labeled tracer of this congener showed that all radioactivity was in the hexane fraction, suggesting that transformation products were hydrophobic.

  8. Time-Trends and Congener Profiles of PBDEs and PCBs in California Peregrine Falcons (Falco peregrinus)

    PubMed Central

    Park, June-Soo; Holden, Arthur; Chu, Vivian; Kim, Michele; Rhee, Alexandra; Patel, Puja; Shi, Yating; Linthicum, Janet; Walton, Brian J.; Mckeown, Karen; Jewell, Nicholas P.; Hooper, Kim

    2010-01-01

    High levels (µg/g lw) of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were measured in peregrine falcon eggs from California (n = 90 eggs from 52 birds, 38 nest sites, collected 1986–2007, ΣPBDEs median = 4.53, range = 0.08–53.1). Over the past 22 years, PBDE levels more than tripled each decade in the eggs, whereas PCB levels had no significant changes. PBDE levels were highest in eggs from major California cities (“Big Cities”), whereas PCBs showed no difference across the regions. For PBDEs, Big City eggs had markedly different patterns from Coastal eggs:BDE-209 and the higher brominated PBDEs (hexa–nona) were dominant congeners in Big City eggs, while BDE-47 and -99 were dominant in Coastal eggs. In many of the birds that gave multiple eggs over time (“time series”), PBDE patterns changed over time: the high proportions of BDE-209 and higher brominated PBDEs (short half-lives) in young birds contrasted with increasingly higher proportions of BDE-153 (long half-life) and other lower brominated PBDEs as the birds aged. These data are consistent with metabolic debromination of BDE-209 (t1/2 = 1–2 weeks) to the lower brominated PBDEs, with accumulation over time of BDE-153 (t1/2 = 3–4 years). In contrast, PCB patterns showed no differences by locations, and did not change over time. Diet (prey birds) may explain the urban PBDE pattern, as the patterns in urban pigeons and peregrines were similar, with high proportions of BDE-209 and the higher-brominated PBDEs. Also, our prey data (feathers from peregrine nests) showed urban peregrines having a higher proportion (>2 fold) of granivorous/opportunistic birds (e.g., “introduced feral” pigeons, mourning doves, starlings) in their diet than coastal peregrines. In summary, these data indicate that BDE-209 exits consumer products as an environmental contaminant to be taken up by wildlife (particularly in urban locations), and undergoes metabolic debromination to the

  9. Time-trends and congener profiles of PBDEs and PCBs in California peregrine falcons (Falco peregrinus).

    PubMed

    Park, June-Soo; Holden, Arthur; Chu, Vivian; Kim, Michele; Rhee, Alexandra; Patel, Puja; Shi, Yating; Linthicum, Janet; Walton, Brian J; McKeown, Karen; Jewell, Nicholas P; Hooper, Kim

    2009-12-01

    High levels (microg/g lw) of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were measured in peregrine falcon eggs from California (n = 90 eggs from 52 birds, 38 nest sites, collected 1986-2007, SigmaPBDEs median = 4.53, range = 0.08-53.1). Over the past 22 years, PBDE levels more than tripled each decade in the eggs, whereas PCB levels had no significant changes. PBDE levels were highest in eggs from major California cities ("Big Cities"), whereas PCBs showed no difference across the regions. For PBDEs, Big City eggs had markedly different patterns from Coastal eggs: BDE-209 and the higher brominated PBDEs (hexa-nona) were dominant congeners in Big City eggs, while BDE-47 and -99 were dominant in Coastal eggs. In many of the birds that gave multiple eggs over time ("time series"), PBDE patterns changed over time: the high proportions of BDE-209 and higher brominated PBDEs (short half-lives) in young birds contrasted with increasingly higher proportions of BDE-153 (long half-life) and other lower brominated PBDEs as the birds aged. These data are consistent with metabolic debromination of BDE-209 (t(1/2) = 1-2 weeks) to the lower brominated PBDEs, with accumulation over time of BDE-153 (t(1/2) = 3-4 years). In contrast, PCB patterns showed no differences by locations, and did not change over time. Diet (prey birds) may explain the urban PBDE pattern, as the patterns in urban pigeons and peregrines were similar, with high proportions of BDE-209 and the higher-brominated PBDEs. Also, our prey data (feathers from peregrine nests) showed urban peregrines having a higher proportion (>2 fold) of granivorous/opportunistic birds (e.g., "introduced feral" pigeons, mourning doves, starlings) in their diet than coastal peregrines. In summary, these data indicate that BDE-209 exits consumer products as an environmental contaminant to be taken up by wildlife (particularly in urban locations), and undergoes metabolic debromination to the banned lower

  10. Sexual receptivity facilitated by unesterified estradiol: Dependence on estrogen and progestin receptors and priming dose of estradiol benzoate.

    PubMed

    Domínguez-Ordóñez, Raymundo; García-Juárez, Marcos; Lima-Hernández, Francisco J; Gómora-Arrati, Porfirio; Blaustein, Jeffrey D; González-Flores, Oscar

    2015-12-01

    In some conditions, female sexual behavior in ovariectomized rats can be induced by continuous exposure of estradiol (E2) alone or by a single injection of a high dose of the long-lasting, esterified estradiol benzoate (EB). However, there are inconsistencies in the literature on the role of estrogens during priming or in the facilitation on female sexual behavior in EB-primed rats, as well as the cellular mechanisms involved. Either subcutaneous (sc) or intracerebral (icv) administration of some doses of free unesterified E2, induced lordosis in EB-primed rats. Either sc or icv injection of E2, immediately prior to testing, induced high levels of sexual receptivity when the female rats were primed with an EB sc injection of 2 μg EB. The roles of progesterone receptor (PR) and estrogen receptor on lordosis induced by sc or icv administration of E2 were explored. Tamoxifen or RU486 administrated sc or icv; each reduced lordosis induced by E2. Similarly, antisense oligonucleotides directed at PR-B or total PR (PR-A + PR-B) administrated icv immediately before EB injection inhibited lordosis induced by daily injections of EB. These results suggest that lordosis facilitated by free E2 is dependent on priming dose of EB. Furthermore both ERs and PRs are involved in this action of E2.

  11. Alkali Metal Carbenoids: A Case of Higher Stability of the Heavier Congeners.

    PubMed

    Molitor, Sebastian; Gessner, Viktoria H

    2016-06-27

    As a result of the increased polarity of the metal-carbon bond when going down the group of the periodic table, the heavier alkali metal organyl compounds are generally more reactive and less stable than their lithium congeners. We now report a reverse trend for alkali metal carbenoids. Simple substitution of lithium by the heavier metals (Na, K) results in a significant stabilization of these usually highly reactive compounds. This allows their isolation and handling at room temperature and the first structure elucidation of sodium and potassium carbenoids. The control of stability was used to control reactivity and selectivity. Hence, the Na and K carbenoids act as selective carbene-transfer reagents, whereas the more labile lithium systems give rise to product mixtures. Additional fine tuning of the M-C interaction by means of crown ether addition further allows for control of the stability and reactivity. PMID:27100278

  12. Herbicidin Congeners, Undecose Nucleosides from an Organic Extract of Streptomyces sp. L-9-10

    PubMed Central

    2015-01-01

    Four new undecose nucleosides (herbicidin congeners), three known herbicidins, and 9-(β-d-arabinofuranosyl)hypoxanthine (Ara-H) were isolated from the organic extract of a fermentation culture of Streptomyces sp. L-9-10 using proton NMR-guided fractionation. Their structures were elucidated on the basis of comprehensive 1D and 2D NMR and mass spectrometry analyses. These structures included 2′-O-demethylherbicidin F (1), 9′-deoxy-8′,8′-dihydroxyherbicidin B (2), 9′-deoxy-8′-oxoherbicidin B (2a), and the 8′-epimer of herbicidin B (3). This is the first detailed assignment of proton and carbon chemical shifts for herbicidins A, B, and F. The isolated compounds were evaluated for cancer chemopreventive potential based on inhibition of tumor necrosis factor alpha (TNF-α)-induced nuclear factor-kappa B (NF-κB) activity. PMID:24533857

  13. Polychlorinated biphenyl congeners in sediment cores from the Upper Mississippi River.

    PubMed

    Martinez, Andres; Schnoebelen, Douglas J; Hornbuckle, Keri C

    2016-02-01

    We determined polychlorinated biphenyls (PCBs) and radionuclide (137)Cs in sediment cores from the Upper Mississippi River (UMR) and the Iowa River, Iowa, at their confluence. Vertical distribution of (137)Cs indicated negligible mixing in the UMR core, while the Iowa River core showed signs of mixing. A clear (137)Cs peak was found in the UMR core, which was correlated to 1963. The PCB vertical distribution in UMR core was similar to the historical trend in Aroclor production observed in Great Lakes cores, with a peak close to the (137)Cs peak, suggesting a date near 1960. In general, PCB congener profiles in both cores resembled the Iowa soil background signal. We concluded that despite evidence of mixing in the Iowa River core, both cores retain the PCB signature of historical and regional environmental exposure. Further, our results indicate that this iconic waterway has a long history of PCBs that reflects national production and use. PMID:26547030

  14. Gateway synthesis of daphnane congeners and their protein kinase C affinities and cell-growth activities

    NASA Astrophysics Data System (ADS)

    Wender, Paul A.; Buschmann, Nicole; Cardin, Nathan B.; Jones, Lisa R.; Kan, Cindy; Kee, Jung-Min; Kowalski, John A.; Longcore, Kate E.

    2011-08-01

    The daphnane diterpene orthoesters constitute a structurally fascinating family of natural products that exhibit a remarkable range of potent biological activities. Although partial activity information is available for some natural daphnanes, little information exists for non-natural congeners or on how changes in structure affect mode of action, function, potency or selectivity. A gateway strategy designed to provide general synthetic access to natural and non-natural daphnanes is described and utilized in the synthesis of two novel members of this class. In this study, a commercially available tartrate derivative was elaborated through a key late-stage diversification intermediate into B-ring yuanhuapin analogues to initiate exploration of the structure-function relationships of this class. Protein kinase C was identified as a cellular target for these agents, and their activity against human lung and leukaemia cell lines was evaluated. The natural product and a novel non-natural analogue exhibited significant potency, but the epimeric epoxide was essentially inactive.

  15. Influence of colloids on sediment-water partition coefficients of polychlorobiphenyl congeners in natural waters

    SciTech Connect

    Baker, J.E.; Capel, P.D.; Eisenreich, S.J.

    1986-11-01

    Measurements of sediment-water partitioning of polychlorobiphenyl (PCB) congeners in Lake Superior provide some of the first field evidence demonstrating the importance of colloids to the fates of highly hydrophobic organic pollutants. Laboratory-derived correlations between sediment-water distribution coefficients and properties of both the contaminant (octanol-water partition coefficient) and the suspended solids (organic carbon content, concentration) do not accurately predict PCB speciation in Lake Superior. This failure can be explained by the presence of colloidal matter with which contaminants may associate and the very low solids concentrations in oligotrophic surface waters. A surprising consequence of such colloid associations is that the observed sediment-water distribution coefficients are independent of properties of highly hydrophobic compounds. A three-phase model including nonfilterable microparticles and macromolecular organic matter shows that colloidal-associated contaminants may be the dominant species in most surface waters. Colloidal associations are therefore likely to significantly impact the geochemistry of hydrophobic pollutants.

  16. Comparing biological effects of estrone (E1) and 17ß-estradiol (E2) in mature fathead minnows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The presence of endocrine active compounds such as estrogens in treated wastewater effluent and their effects on aquatic life are causing concern among aquatic resource managers. Among the natural estrogens are 17ß-estradiol, 17a-estradiol, and estrone. Although 17ß-estradiol has received significa...

  17. Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation

    PubMed Central

    Cui, Yue; Franciszkiewicz, Katarzyna; Mburu, Yvonne K.; Mondot, Stanislas; Le Bourhis, Lionel; Premel, Virginie; Martin, Emmanuel; Kachaner, Alexandra; Duban, Livine; Ingersoll, Molly A.; Rabot, Sylvie; Jaubert, Jean; De Villartay, Jean-Pierre; Soudais, Claire; Lantz, Olivier

    2015-01-01

    Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%–10% in blood). Despite strong evolutionary conservation of the invariant TCR-α chain and restricting molecule MR1, this population is rare in laboratory mouse strains (≈0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-α locus and led to higher usage of the distal Vα segments, including Vα19. We generated a MAIThi congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory (CD44+) CD4–CD8lo/neg T cells with tissue-homing properties (CCR6+CCR7–). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18Rα, and IL-12Rβ and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptor γ (RORγt). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the MAIThi congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease. PMID:26524590

  18. Feasibility of Trace Alcohol Congener Detection and Identification Using Laser-Induced Breakdown Spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhang, Jialiang; Wang, Shangmin; Zhao, Lixian; Liu, Liying; Wang, Dezhen

    2014-12-01

    In this paper, a feasible scheme is reported for the detection and identification of trace alcohol congeners that have identical elemental composition using laser-induced breakdown spectroscopy (LIBS). In the scheme, an intensive pulsed laser is used to break down trace alcohol samples and the optical emission spectra of the induced plasma are collected for the detection and identification of alcohol molecules. In order to prepare trace alcohol samples, pure ethanol or methanol is bubbled by argon carrier gas and then mixed into matrix gases. The key issue for the scheme is to constitute indices from the LIBS data of the alcohol samples. Two indices are found to be suitable for alcohol detection and identification. One is the emission intensity ratio (denoted as H/C) of the hydrogen line (653.3 nm) to the carbon line (247.9 nm) for identification and the other is the ratio of the carbon line (as C/Ar) or the hydrogen line (as H/Ar) to the argon lines (866.7 nm) for quantitative detection. The calibration experiment result shows that the index H/C is specific for alcohol congeners while almost being independent of alcohol concentration. In detail, the H/C keeps a specific constant of 34 and 23 respectively for ethanol and methanol. In the meanwhile, the C/Ar and H/Ar indices respond almost linearly to the alcohol concentration below 1300 ppm, and are therefore competent for concentration measurement. With the indices, trace alcohol concentration measurement achieves a limit of 140 ppm using a laser pulse energy of 300 mJ.

  19. Mucosal-associated invariant T cell-rich congenic mouse strain allows functional evaluation.

    PubMed

    Cui, Yue; Franciszkiewicz, Katarzyna; Mburu, Yvonne K; Mondot, Stanislas; Le Bourhis, Lionel; Premel, Virginie; Martin, Emmanuel; Kachaner, Alexandra; Duban, Livine; Ingersoll, Molly A; Rabot, Sylvie; Jaubert, Jean; De Villartay, Jean-Pierre; Soudais, Claire; Lantz, Olivier

    2015-11-01

    Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%-10% in blood). Despite strong evolutionary conservation of the invariant TCR-α chain and restricting molecule MR1, this population is rare in laboratory mouse strains (≈0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-α locus and led to higher usage of the distal Vα segments, including Vα19. We generated a MAIThi congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory (CD44+) CD4-CD8lo/neg T cells with tissue-homing properties (CCR6+CCR7-). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18Rα, and IL-12Rβ and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptor γ (RORγt). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the MAIThi congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease.

  20. Effects of nitric oxide and its congeners on sickle red blood cell deformability

    PubMed Central

    Belanger, Andrea M.; Keggi, Christian; Kanias, Tamir; Gladwin, Mark T.; Kim-Shapiro, Daniel B.

    2015-01-01

    BACKGROUND Sickle cell disease is characterized by hemoglobin (Hb) polymerization upon deoxygenation. Polymerization causes the sickle cells to become rigid and misshapen (sickling). Red blood cell (RBC) dehydration greatly increases polymerization. Cycles of sickling and unsickling cause an influx of calcium that leads to loss of potassium via the calcium-activated Gardos channel which dehydrates the cells leading to increased polymerization. In this study effects of NO and its congeners on RBC deformability were examined, focusing on sickle red blood cells. STUDY DESIGN AND METHODS Red blood cells from patients with sickle cell disease and from non-patients were exposed to various compounds that release NO or its congeners. Intracellular calcium was increased using a calcium ionophore or cycling of oxygen tension for sickle red blood cells. Deformability was measured by laser-assisted osmotic gradient ektacytometry. RESULTS Consistent with a previous report, sodium nitroprusside (SNP) was found to protect against calcium-induced loss of deformability in normal red blood cells, but (contrary to some previous reports) no effect of any NO donors was observed when calcium influx was not induced. Importantly, in studies of deoxygenation-induced dehydration of sickle RBCs, SNP resulted in substantial improvements in deformability (p=0.036) and hydration (p=0.024). Sodium nitrite showed similar trends. SNP was shown to have no effect on calcium influx, but reduced potassium efflux. CONCLUSION These data suggest SNP and perhaps certain nitrogen oxides (like nitrite) inhibit the Gardos channel and may be able to protect sickle cells from dehydration and thereby improve outcome in the disease. PMID:25912054

  1. Accumulation of polychlorinated biphenyl congeners from Lake Champlain sediments by Mysis relicta

    SciTech Connect

    Lester, D.C.; McIntosh, A. . Vermont Water Resources and Lake Studies Center)

    1994-11-01

    Polychlorinated biphenyl (PCB) levels in lake trout (Salvelinus namaycush) from Lake Champlain often exceed the F.D.A. tolerance level of 2 [mu]g/g (wet weight). Of added concern are recent studies that suggest a relationship between the dioxin-like properties of non-ortho-substituted PCB congeners and impaired lake trout egg hatchability. Dietary accumulation of PCBs is thought to be an important exposure route for fish. The epibenthic freshwater shrimp Mysis relicta is an integral part of the benthic and pelagic food web in lake Champlain and may act as a link between PCBs in sediments and lake trout. Previous investigations have shown that diurnal migrations of mysids enhance the movement and distribution of toxic contaminants, effectively coupling the benthic and pelagic zones. The objective of this research was to examine the role contaminated sediments play in the transfer of PCBs to mysids. Bioaccumulation was assessed by exposing mysids to such sediments in two ways: (a) with organisms screened from sediments; and (b) with organisms in direct contact with sediments. Accumulation of PCBs over the course of the 24-day exposure period was examined on the following days: 0, 3, 6, 12, 21, and 24. Eighty-nine individual PCB congeners were measured in tissue and sediment. Mysids in direct contact with sediments accumulated significantly higher levels of PCBs than did organisms screened from sediments. Mysids accumulated substantial levels of PCBs, suggesting they may play an important part in the transfer of PCBs from sediments into the Lake Champlain food web. It is clear from this research that sediments can play a critical role in the accumulation of PCBs by mysids.

  2. Displacement of Tetropium cinnamopterum (Coleoptera: Cerambycidae) by Its Invasive Congener Tetropium fuscum.

    PubMed

    Dearborn, Kenneth W; Heard, Stephen B; Sweeney, Jon; Pureswaran, Deepa S

    2016-08-01

    We examined the native community of insects interacting with an invasive species, Tetropium fuscum (F.) (Coleoptera: Cerambycidae), in its new range to explore reasons for the invader's relatively slow spread. Tetropium fuscum is a European spruce borer established in Nova Scotia since at least 1990, but it has spread only about 125 km from its site of introduction. We compared the densities of Tetropium spp., their known parasitoids, and the community of wood-boring insects at sites located within the invasion zone in Nova Scotia versus well outside this zone, in New Brunswick, Canada. Using red spruce trees stressed by girdling or felling, we tested whether: 1) T. fuscum had altered the native wood-boring community; 2) T. fuscum displaced a native congener, Tetropium cinnamopterum (Kirby); and 3) parasitism rates of Tetropium spp. differed between the invaded and noninvaded zones. Both Tetropium spp. and their parasitoid wasps emerged exclusively from felled trees as opposed to girdled trees. We found no difference in community diversity inside versus outside the invasion zone. The combined densities of both Tetropium spp. and their overall parasitism rates also did not differ between zones, but T. cinnamopterum density was significantly greater outside the invasion zone, suggesting T. fuscum may displace the native congener where they are sympatric. Our results suggest that the native and invasive Tetropium spp. act as a single functional species in the invasion zone. We speculate that natural control agents (predators, parasitoids, and competitors) might be limiting the rate of spread of T. fuscum. PMID:27247305

  3. Detection of estradiol-17β during a mass coral spawn

    NASA Astrophysics Data System (ADS)

    Atkinson, S.; Atkinson, M. J.

    1992-04-01

    The steroid estradiol-17β (E2) is associated with female gametogenesis in all vertebrates and many invertebrates. This is the first report of estrogens in scleractinian corals. Seawater and egg slicks were collected during a mass coral spawn at Ningaloo reef, Western Australia for the measurement of total phosphate (TP) and E2. Total P in the water column increased 600 times, from 0.5μM to 300μM. Concentrations of E2 increased nearly 8 fold during the spawn, from 55 to 420 pg/100 ml seawater. Coral eggs collected from egg slicks contained 368±40 pg E2/g dry wt of eggs. Estrogen may be a key hormone in a simple endocrine system of scleractinian corals that synchronizes growth and development of coral oocytes. Its potential role in triggering spawning via chemical messengers in the water column warrants further research.

  4. Laccase mediated transformation of 17β-estradiol in soil.

    PubMed

    Singh, Rashmi; Cabrera, Miguel L; Radcliffe, David E; Zhang, Hao; Huang, Qingguo

    2015-02-01

    It is known that 17β-estradiol (E2) can be transformed by reactions mediated by some oxidoreductases such as laccase in water. Whether or how such reactions can happen in soil is however unknown although they may significantly impact the environmental fate of E2 that is introduced to soil by land application of animal wastes. We herein studied the reaction of E2 in a model soil mediated by laccase, and found that the reaction behaviors differ significantly from those in water partly because of the dramatic difference in laccase stability. We also examined E2 transformation in soil using (14)C-labeling in combination with soil organic matter extraction and size exclusion chromatography, which indicated that applied (14)C radioactivity was preferably bound to humic acids. The study provides useful information for understanding the environmental fate of E2 and for developing a novel soil remediation strategy via enzyme-enhanced humification reactions. PMID:25489747

  5. Relationship between Carotenoids, Retinol, and Estradiol Levels in Older Women

    PubMed Central

    Maggio, Marcello; de Vita, Francesca; Lauretani, Fulvio; Bandinelli, Stefania; Semba, Richard D.; Bartali, Benedetta; Cherubini, Antonio; Cappola, Anne R.; Ceda, Gian Paolo; Ferrucci, Luigi

    2015-01-01

    Background. In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2) in a cohort of late post-menopausal women. Methods. We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998–2000) by High-Performance Liquid Chromatography. Estradiol and testosterone (T) levels were assessed by Radioimmunometry (RIA) and testosterone-to-estradiol ratio (T/E2), as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1) and further adjusted for other confounders including Body Mass Index (BMI) BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2) were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. Results. After adjustment for age, α-carotene (β ± SE = −0.01 ± 0.004, p = 0.02) and β-carotene (β ± SE = −0.07 ± 0.02, p = 0.0007) were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01). After adjustment for other confounders (Model 2), the inverse relationship between α-carotene (β ± SE = −1.59 ± 0.61, p = 0.01), β-carotene (β ± SE = −0.29 ± 0.08, p

  6. TISSUE DISTRIBUTION OF PCBS AND ORGANOCHLORINE PESTICIDES IN ALASKAN NORTHERN FUR SEALS: COMPARISON OF VARIOUS CONGENER CLASSIFICATION SCHEMES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are believed to adversely affect reproduction and cause health problems in Pinnipeds 1-4. In this study, 145 PCB congeners and OCPs were analyzed in 10 juvenile male northern fur seals, Callorhinus ursinus, collected from Alaskan...

  7. Analysis of major congeners of polybromobiphenyls and polybromodiphenyl ethers in office dust using high resolution gas chromatography-mass spectrometry.

    PubMed

    Kefeni, Kebede K; Okonkwo, Jonathan O

    2012-05-01

    The study focused on analysis of polybromobiphenyls (PBBs) and polybromodiphenyl ethers (PBDEs) congeners in office dust obtained in Pretoria, South Africa. Of the 32 congeners considered for identification, (BB-1, 2, 4, 10, 15, 26, 29, 30, 31, 38, 49, 80, 103, 153, 155, 209 and BDE-3, 15, 17, 28, 47, 66, 77, 85, 99, 100, 126, 138, 153, 154, 183, 209) only BB-2, 4, 30, 153, 209 and BDE-47, 66, 85, 99, 153 and 209 congeners were detected. The sum of PBBs concentration detected in office dust ranged from congeners detected. Concentrations of PBDEs detected in this study are substantially lower than reported in office dust in developed countries. PMID:22386464

  8. Molecular phylogeography of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae) and genetic relationships with congeners using cytochrome b gene marker.

    PubMed

    Yong, Hoi-Sen; Eamsobhana, Praphathip; Song, Sze-Looi; Prasartvit, Anchana; Lim, Phaik-Eem

    2015-08-01

    Angiostrongylus cantonensis is an important emerging zoonotic parasite causing human eosinophilic meningitis (or meningoencephalitis) in many parts of the world. To-date there is only a single study using mitochondrial cytochrome b (CYTB) gene to determine its genetic structure in eight geographical localities in Thailand. The present study examined the molecular phylogeography of this rat lungworm and its phylogenetic relationship with congeners using CYTB gene marker. A total of 15 CYTB haplotypes was found in 37 sequences from 14 geographical localities (covering north, west, east, central and south regions) in Thailand. These CYTB haplotypes were distinct from those of A. cantonensis for China and Hawaii. In Thailand, some CYTB haplotypes appeared to be confined to specific geographical localities. The partial CYTB DNA nucleotide sequences separated unequivocally the A. cantonensis isolates of Thailand, China and Hawaii as well as the congeners Angiostrongylus malaysiensis, A. costaricensis and Angiostrongylus vasorum, with A. malaysiensis grouped with A. cantonensis and A. costaricensis grouped with A. vasorum. Likewise the congeners of Metastrongylus and Onchocerca genera could also be clearly differentiated. The present study added two new definitive hosts (Bandicota savilei and Rattus losea) and three new localities (Mae Hong Son in the north, Tak in the west, and Phang Nga in the south) for A. malaysiensis in Thailand, indicating its wide occurrence in the country. Three CYTB haplotypes were found in the Thailand samples of A. malaysiensis. In addition to differentiation of congeners, CYTB gene marker could be used for determining the genetic diversity of a given population/taxon.

  9. Novel double-congenic strain reveals effects of spontaneously hypertensive rat chromosome 2 on specific lipoprotein subfractions and adiposity.

    PubMed

    Seda, Ondrej; Sedová, Lucie; Liska, Frantisek; Krenová, Drahomíra; Prejzek, Vratislav; Kazdová, Ludmila; Tremblay, Johanne; Hamet, Pavel; Kren, Vladimír

    2006-10-01

    We have developed a new, double-congenic rat strain BN-Lx.SHR2, which carries two distinct segments of chromosome 2 introgressed from the spontaneously hypertensive rat strain (SHR) into the genetic background of congenic strain BN-Lx, which was previously shown to express variety of metabolic syndrome features. In 16-wk-old male rats of BN-Lx and BN-Lx.SHR2 strains, we compared their glucose tolerance and triacylglycerol and cholesterol concentrations in 20 lipoprotein subfractions and the lipoprotein particle sizes under conditions of feeding standard and high-sucrose diets. Introgression of two distinct SHR-derived chromosome 2 segments resulted in decreased adiposity together with aggravation of glucose intolerance in the double-congenic strain. The BN-Lx.SHR2 rats were more sensitive to sucrose-induced rise in triacylglycerolemia. Although the total cholesterol concentrations of the two strains were comparable after the standard diet and even lower in BN-Lx.SHR2 after sucrose feeding, detailed analysis revealed that under both dietary conditions, the double-congenic strain had significantly higher cholesterol concentrations in low-density lipoprotein fractions and lower high-density lipoprotein fractions. We established a new inbred model showing dyslipidemia and mild glucose intolerance without obesity, attributable to specific genomic regions. For the first time, the chromosome 2 segments of SHR origin are shown to influence other than blood pressure-related features of metabolic syndrome or to be involved in relevant nutrigenomic interactions.

  10. Subchronic inhalation exposure study of an airborne polychlorinated biphenyl (PCB) mixture resembling the Chicago ambient air congener profile

    PubMed Central

    Hu, Xin; Adamcakova-Dodd, Andrea; Lehmler, Hans-Joachim; Hu, Dingfei; Hornbuckle, Keri; Thorne, Peter S

    2013-01-01

    Although inhalation of atmospheric PCBs is the most universal exposure route and has become a substantial concern in urban areas, research is lacking to determine the body burden of inhaled PCBs and consequent health effects. To reflect the Chicago airshed environment and mimic the PCB profile in Chicago air, we generated vapors from a Chicago Air Mixture (CAM). Sprague-Dawley rats were exposed to the CAM vapor for 1.6 hr/day via nose-only inhalation for 4 wks, 520±10 μg/m3. Congener-specific quantification in tissue and air samples was performed by GC/MS/MS. In contrast to the lower-chlorinated congener enriched vapor, body tissues mainly contained tri- to hexachlorobiphenyls. Congener profiles varied between vapor and tissues, and among different organs. The toxic equivalence (TEQ) and neurotoxic equivalence (NEQ) were also investigated for tissue distribution. We evaluated a variety of endpoints to catalog the effects of long-term inhalation exposure, including immune responses, enzyme induction, cellular toxicity and histopathologic abnormalities. GSSG/GSH ratio was increased in blood of exposed animals, accompanied by elevation of hematocrit. This study demonstrated that inhalation contributed to the body burden of mostly tri- to hexachlorobiphenyls and produced a distinct profile of congeners in tissue, yet minimal toxicity was found at this exposure dose estimated at 134 μg/rat. PMID:22846166

  11. Phenotypic plasticity of invasive Alternanthera philoxeroides in relation to different water availability, compared to its native congener

    NASA Astrophysics Data System (ADS)

    Geng, Yu-Peng; Pan, Xiao-Yun; Xu, Cheng-Yuan; Zhang, Wen-Ju; Li, Bo; Chen, Jia-Kuan

    2006-11-01

    Phenotypic plasticity and genetic differentiation are two possible mechanisms that plants use to cope with varying environments. Although alligator weed ( Alternanthera philoxeroides) possesses very low genetic diversity, this alien weed has successfully invaded diverse habitats with considerably varying water availability (from swamps to dry lands) in China. In contrast, its native congener ( Alternanthera sessilis) has a much narrower ecological breadth, and is usually found in moist habitats. To understand the mechanisms underlying the contrasting pattern, we performed a greenhouse experiment to compare the reaction norms of alligator weed with those of its native congener, in which water availability was manipulated. Our results revealed that the two congeners had similar direction of phenotypic plasticity. However, A. philoxeroides showed greater plasticity in amount than did A. sessilis in many traits examined during the switch from wet to drought treatment. Nearly all of the phenotypic variance in A. philoxeroides could be ascribed to plasticity, while A. sessilis had a much higher fraction of phenotypic variance that could be explained by genotypic variation. These interspecific differences in plastic responses to variable water availability partially explained the difference in spatial distribution of the two congeners.

  12. Analysis of major congeners of polybromobiphenyls and polybromodiphenyl ethers in office dust using high resolution gas chromatography-mass spectrometry.

    PubMed

    Kefeni, Kebede K; Okonkwo, Jonathan O

    2012-05-01

    The study focused on analysis of polybromobiphenyls (PBBs) and polybromodiphenyl ethers (PBDEs) congeners in office dust obtained in Pretoria, South Africa. Of the 32 congeners considered for identification, (BB-1, 2, 4, 10, 15, 26, 29, 30, 31, 38, 49, 80, 103, 153, 155, 209 and BDE-3, 15, 17, 28, 47, 66, 77, 85, 99, 100, 126, 138, 153, 154, 183, 209) only BB-2, 4, 30, 153, 209 and BDE-47, 66, 85, 99, 153 and 209 congeners were detected. The sum of PBBs concentration detected in office dust ranged from congeners detected. Concentrations of PBDEs detected in this study are substantially lower than reported in office dust in developed countries.

  13. Response to Ecological Risk Assessment Forum Request for Information on the Benefits of PCB Congener-Specific Analyses

    EPA Science Inventory

    In August, 2001, the Ecological Risk Assessment Forum (ERAF) submitted a formal question to the Ecological Risk Assessment Support Center (ERASC) on the benefits of evaluating PCB congeners in environmental samples. This question was developed by ERAF members Bruce Duncan and Cla...

  14. GC/MS ANALYSIS OF PCB CONGENERS IN BLOOD OF THE HARBOR SEAL PHOCA VITULINA FROM SAN FRANCISCO BAY

    EPA Science Inventory

    Here we report a validated technique for quantifying up to 20 specific PCB congeners in 1-2 g samples of whole blood with a detection limit below 1 ng/g (ppb) wet weight. Specimens were analyzed from 14 harbor seals sampled in south San Francisco Bay, California during 1991-1992....

  15. Polychlorinated biphenyl congener patterns in tree swallows (Tachycineta bicolor) nesting in the Housatonic River watershed, western Massachusetts, USA, using a novel statistical approach.

    PubMed

    Custer, Christine M; Read, Lorraine B

    2006-07-01

    A novel application of a commonly used statistical approach was used to examine differences in polychlorinated biphenyl (PCB) congener patterns among locations and sample matrices in tree swallows (Tachycineta bicolor) nesting in the Housatonic River watershed in western Massachusetts, USA. The most prevalent PCB congeners in tree swallow tissue samples from the Housatonic River watershed were Ballsmitter Zell numbers 153, 138, 180, 187, 149, 101, and 170. These congeners were seven of the eight most prevalent congeners in Aroclor 1260, the PCB mixture that was the primary source of contamination in the Housatonic River system. Using paired-Euclidean distances and tolerance limits, it was demonstrated that congener patterns in swallow tissues from sites on the main stem of the Housatonic River were more similar to one another than to two sites upstream of the contamination or from a nearby reference area. The congener patterns also differed between the reference area and the two upstream tributaries and between the two tributaries. These pattern differences were the same in both pipper (eggs or just hatched nestlings) and 12-day-old nestling samples. Lower-chlorinated congeners appeared to be metabolized in nestlings and pippers compared to diet, and metabolized more in pippers compared to nestlings. Euclidean distances and tolerance limits provide a simple and statistically valid method to compare PCB congener patterns among groups.

  16. Day length and estradiol affect same-sex affiliative behavior in the female meadow vole

    PubMed Central

    Beery, Annaliese K.; Loo, Theresa J.; Zucker, Irving

    2008-01-01

    Non-sexual social bonding between adult mammals remains poorly understood, despite its importance in many species. Female meadow voles are territorial and nest alone in long summer day lengths when circulating estradiol concentrations are high, but cohabit in groups in short winter photoperiods when estradiol secretion is low. The influence of day length and estradiol on same-sex huddling behavior was assessed in adult female pairs housed together in long day lengths (LDs) or short day lengths (SDs) from weaning. The behavior of intact, ovariectomized, and estradiol-treated ovariectomized females from each photoperiod was assessed during 3 hour partner preference tests. Intact SD voles, unlike intact LD voles, spent the majority of the test in proximity to their cage mates. Estradiol treatment of SD voles significantly reduced time spent huddling with the partner. Neither ovariectomy nor estradiol treatment significantly affected the amount of time LD females spent in contact with their partners. Low estradiol availability is therefore a necessary but not sufficient condition for maintenance of high levels of huddling. These results establish that ovarian hormones interact with photoperiod to affect same-sex social behavior. PMID:18387611

  17. High estradiol levels improve false memory rates and meta-memory in highly schizotypal women.

    PubMed

    Hodgetts, Sophie; Hausmann, Markus; Weis, Susanne

    2015-10-30

    Overconfidence in false memories is often found in patients with schizophrenia and healthy participants with high levels of schizotypy, indicating an impairment of meta-cognition within the memory domain. In general, cognitive control is suggested to be modulated by natural fluctuations in oestrogen. However, whether oestrogen exerts beneficial effects on meta-memory has not yet been investigated. The present study sought to provide evidence that high levels of schizotypy are associated with increased false memory rates and overconfidence in false memories, and that these processes may be modulated by natural differences in estradiol levels. Using the Deese-Roediger-McDermott paradigm, it was found that highly schizotypal participants with high estradiol produced significantly fewer false memories than those with low estradiol. No such difference was found within the low schizotypy participants. Highly schizotypal participants with high estradiol were also less confident in their false memories than those with low estradiol; low schizotypy participants with high estradiol were more confident. However, these differences only approached significance. These findings suggest that the beneficial effect of estradiol on memory and meta-memory observed in healthy participants is specific to highly schizotypal individuals and might be related to individual differences in baseline dopaminergic activity.

  18. Estradiol administration to ovariectomized rats potentiates mephedrone-induced disruptions of nonspatial learning.

    PubMed

    Weed, Peter F; Leonard, Stuart T; Sankaranarayanan, Ananthakrishnan; Winsauer, Peter J

    2014-03-01

    Mephedrone (4-methylmethcathinone) has been found in several over-the-counter products that are abused by humans, but very little is known about its behavioral effects and abuse liability. The present study examined the effects of mephedrone (1-10 mg/kg) on learning in female rats, as well as its interaction with the ovarian hormone estradiol. More specifically, female rats were trained to respond under a multiple schedule of repeated acquisition and performance of response sequences and then ovariectomized. Following ovariectomy, mephedrone dose-effect curves were obtained during periods of 17β-estradiol administration and periods without estradiol administration. Unlike mephedrone, which was administered acutely (i.p.) before the experimental sessions, 17β-estradiol was administered via subcutaneous Silastic capsules containing 25% 17β-estradiol and 75% cholesterol. In general, mephedrone produced dose-dependent rate-decreasing and error-increasing effects in the acquisition and performance components of the schedule in all subjects. However, when estradiol was present, three of the four rats were more sensitive to the rate-decreasing effects of mephedrone, and all of the subjects were more sensitive to its error-increasing effects. These data indicate that estradiol can potentiate the disruptive effects of mephedrone on both the acquisition and performance of complex behavior in female rats.

  19. Pharmacokinetic studies of solubilized estradiol given vaginally in a novel softgel capsule

    PubMed Central

    Pickar, J. H.; Amadio, J. M.; Bernick, B. A.; Mirkin, S.

    2016-01-01

    Abstract Objective To evaluate the bioavailability and safety of a novel vaginal capsule containing solubilized bioidentical 17β-estradiol for vulvar and vaginal atrophy and compare its pharmacokinetics with that of an approved vaginal estradiol tablet in healthy postmenopausal women. Methods Two randomized, single-dose, two-way cross-over, relative bioavailability trials compared the pharmacokinetics of a solubilized vaginal estradiol softgel capsule (TX-004HR, test) with that of a vaginal estradiol tablet (Vagifem®, reference) in postmenopausal women (aged 40–65 years) at 10-μg and 25-μg doses. In each study, women were randomly assigned to receive a single dose of the test capsule or reference tablet, followed by a single dose of the alternate drug after a 14-day washout. Results Thirty-five women completed the 10-μg study and 36 completed the 25-μg study. Significantly lower systemic levels of estradiol, estrone, and estrone sulfate at both doses of the test product were observed compared with equivalent doses of the reference product, with lower AUC0-24 and C max and earlier t max. No adverse events were reported in either trial. Conclusion TX-004HR, a novel estradiol vaginal softgel capsule, exhibited significantly lower systemic exposure than equivalent doses of an approved vaginal estradiol tablet at both 10-μg and 25-μg doses. Both doses of each product were safe and well-tolerated. PMID:26857443

  20. Estradiol decreases cortical reactive astrogliosis after brain injury by a mechanism involving cannabinoid receptors.

    PubMed

    López Rodríguez, Ana Belén; Mateos Vicente, Beatriz; Romero-Zerbo, Silvana Y; Rodriguez-Rodriguez, Noé; Bellini, María José; Rodriguez de Fonseca, Fernando; Bermudez-Silva, Francisco Javier; Azcoitia, Iñigo; Garcia-Segura, Luis M; Viveros, María-Paz

    2011-09-01

    The neuroactive steroid estradiol reduces reactive astroglia after brain injury by mechanisms similar to those involved in the regulation of reactive gliosis by endocannabinoids. In this study, we have explored whether cannabinoid receptors are involved in the effects of estradiol on reactive astroglia. To test this hypothesis, the effects of estradiol, the cannabinoid CB1 antagonist/inverse agonist AM251, and the cannabinoid CB2 antagonist/inverse agonist AM630 were assessed in the cerebral cortex of male rats after a stab wound brain injury. Estradiol reduced the number of vimentin immunoreactive astrocytes and the number of glial fibrillary acidic protein immunoreactive astrocytes in the proximity of the wound. The effect of estradiol was significantly inhibited by the administration of either CB1 or CB2 receptor antagonists. The effect of estradiol may be in part mediated by alterations in endocannabinoid signaling because the hormone increased in the injured cerebral cortex the messenger RNA levels of CB2 receptors and of some of the enzymes involved in the synthesis and metabolism of endocannabinoids. These findings suggest that estradiol may decrease reactive astroglia in the injured brain by regulating the activity of the endocannabinoid system.

  1. The role of histamine in estradiol-induced conditioned consumption reductions.

    PubMed

    Hintiryan, Houri; Hayes, Unja L; Chambers, Kathleen C

    2005-01-31

    Conditioned consumption reductions (CCRs) develop toward novel taste stimuli as a consequence of associating those tastes with certain physiological changes. Few studies have focused on the neurochemical basis of this learned behavior. The purpose of these experiments was to reexamine the role of histamine in CCRs elicited by estradiol. Previous studies have suggested that histamine mediates CCRs induced by radiation, centrifugal rotation, and estradiol. However, because the animals were trained in a drug state, but tested in a nondrug state, it is possible that state-dependent learning confounded the results of these studies. The following series of experiments was performed to test this possibility for estradiol-induced CCRs. Implementing our own methodologies in Experiment 1, we demonstrated that an estradiol-induced CCR was blocked by treatment with the histamine 1 receptor blocker, chlorpheniramine maleate, before sucrose consumption during acquisition. In Experiment 2, identical states were maintained during acquisition and extinction by administering chlorpheniramine prior to sucrose exposure during both phases. The results indicated that chlorpheniramine blocked the estradiol-induced CCR. However, circumventing state-dependency in Experiment 3 by administering chlorpheniramine following exposure to sucrose during acquisition augmented the estradiol CCR. Taken together, the results of these experiments suggest that the ability of chlorpheniramine to abolish estradiol-induced CCRs is not due to state-dependency or to the antihistaminergic properties of chlorpheniramine. It is proposed that the results of all of the experiments can be accounted for by the aversive properties of chlorpheniramine.

  2. 17 beta-estradiol modulates GABAergic synaptic transmission and tonic currents during development in vitro.

    PubMed

    Pytel, Maria; Wójtowicz, Tomasz; Mercik, Katarzyna; Sarto-Jackson, Isabella; Sieghart, Werner; Ikonomidou, Chrysanthy; Mozrzymas, Jerzy W

    2007-05-01

    Estrogens exert a variety of modulatory effects on the structure and function of the nervous system. In particular, 17 beta-estradiol was found to affect GABAergic inhibition in adult animals but its action on GABAergic currents during development has not been elucidated. In the present study, we investigated the effect of 17 beta-estradiol on hippocampal neurons developing in vitro. In this model, mIPSC kinetics showed acceleration with age along with increased alpha1 subunit expression, similarly as in vivo. Long-term treatment with 17 beta-estradiol increased mIPSC amplitudes in neurons cultured for 6-8 and 9-11DIV and prolonged the mIPSC decaying phase only in the 9-11DIV group. The time needed for the onset of 17 beta-estradiol effect on mIPSC amplitude was approximately 48 h. In the period of 9-11DIV, treatment with 17 beta-estradiol strongly reduced the tonic conductance activated by low GABA concentrations. The effects of 17 beta-estradiol on mIPSCs and tonic conductance were not correlated with any change in expression of considered GABAAR subunits (alpha1-3, alpha5-6, gamma2) while alpha4 and delta subunits were at the detection limit. In conclusion, we provide evidence that 17 beta-estradiol differentially affects the phasic and tonic components of GABAergic currents in neurons developing in vitro.

  3. Day length and estradiol affect same-sex affiliative behavior in the female meadow vole.

    PubMed

    Beery, Annaliese K; Loo, Theresa J; Zucker, Irving

    2008-06-01

    Non-sexual social bonding between adult mammals is poorly understood, despite its importance in many species. Female meadow voles are territorial and nest alone in long summer day lengths when circulating estradiol concentrations are high, but cohabit in groups in short winter photoperiods when estradiol secretion is low. The influence of day length and estradiol on same-sex huddling behavior was assessed in adult female pairs housed together in long day lengths (LDs) or short day lengths (SDs) from weaning. The behavior of intact, ovariectomized, and estradiol-treated ovariectomized females from each photoperiod was assessed during 3 h partner-preference tests. Intact SD voles, unlike intact LD voles, spent the majority of the test in proximity to their cage-mates. Estradiol treatment of SD voles significantly reduced time spent huddling with the partner. Neither ovariectomy nor estradiol treatment significantly affected the amount of time LD females spent in contact with their partners. Low estradiol availability is therefore a necessary but not sufficient condition for maintenance of high levels of huddling. These results establish that ovarian hormones interact with photoperiod to affect same-sex social behavior.

  4. High estradiol levels improve false memory rates and meta-memory in highly schizotypal women.

    PubMed

    Hodgetts, Sophie; Hausmann, Markus; Weis, Susanne

    2015-10-30

    Overconfidence in false memories is often found in patients with schizophrenia and healthy participants with high levels of schizotypy, indicating an impairment of meta-cognition within the memory domain. In general, cognitive control is suggested to be modulated by natural fluctuations in oestrogen. However, whether oestrogen exerts beneficial effects on meta-memory has not yet been investigated. The present study sought to provide evidence that high levels of schizotypy are associated with increased false memory rates and overconfidence in false memories, and that these processes may be modulated by natural differences in estradiol levels. Using the Deese-Roediger-McDermott paradigm, it was found that highly schizotypal participants with high estradiol produced significantly fewer false memories than those with low estradiol. No such difference was found within the low schizotypy participants. Highly schizotypal participants with high estradiol were also less confident in their false memories than those with low estradiol; low schizotypy participants with high estradiol were more confident. However, these differences only approached significance. These findings suggest that the beneficial effect of estradiol on memory and meta-memory observed in healthy participants is specific to highly schizotypal individuals and might be related to individual differences in baseline dopaminergic activity. PMID:26292620

  5. Effects of estradiol and FSH on leptin levels in women with suppressed pituitary

    PubMed Central

    2012-01-01

    Background Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. Methods A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student’s t-test and Pearson’s correlation test. Results We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. Conclusions This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH. PMID:22703959

  6. Day length and estradiol affect same-sex affiliative behavior in the female meadow vole.

    PubMed

    Beery, Annaliese K; Loo, Theresa J; Zucker, Irving

    2008-06-01

    Non-sexual social bonding between adult mammals is poorly understood, despite its importance in many species. Female meadow voles are territorial and nest alone in long summer day lengths when circulating estradiol concentrations are high, but cohabit in groups in short winter photoperiods when estradiol secretion is low. The influence of day length and estradiol on same-sex huddling behavior was assessed in adult female pairs housed together in long day lengths (LDs) or short day lengths (SDs) from weaning. The behavior of intact, ovariectomized, and estradiol-treated ovariectomized females from each photoperiod was assessed during 3 h partner-preference tests. Intact SD voles, unlike intact LD voles, spent the majority of the test in proximity to their cage-mates. Estradiol treatment of SD voles significantly reduced time spent huddling with the partner. Neither ovariectomy nor estradiol treatment significantly affected the amount of time LD females spent in contact with their partners. Low estradiol availability is therefore a necessary but not sufficient condition for maintenance of high levels of huddling. These results establish that ovarian hormones interact with photoperiod to affect same-sex social behavior. PMID:18387611

  7. Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women

    NASA Technical Reports Server (NTRS)

    Ettinger, B.; Genant, H. K.; Steiger, P.; Madvig, P.

    1992-01-01

    With the use of a double-blind, randomized, dose-ranging design, we tested during an 18-month period the degree of protection against postmenopausal bone loss afforded by micronized 17 beta-estradiol in dosages of 0.5, 1.0, and 2.0 mg. All subjects received supplementation to ensure a minimum of 1500 mg calcium daily. Fifty-one subjects completed at least 1 year of follow-up bone density measurements by quantitative computed tomography and by single- and dual-photon absorptiometry. In the placebo group spinal trabecular bone density decreased 4.9% annually (p less than 0.001), whereas in those taking micronized 17 beta-estradiol bone density tended to increase (annual increases of 0.3% in the 0.5 mg micronized 17 beta-estradiol group, 1.8% in the 1.0 mg micronized 17 beta-estradiol group, and 2.5% in the 2.0 mg micronized 17 beta-estradiol group). After completing the double-blind phase, 41 subjects completed an additional 18 months of follow-up while taking 1.0 mg micronized 17 beta-estradiol. During this time one third of the subjects were randomly assigned to discontinue calcium supplements. Among those who previously received placebo, trabecular bone density increased 4.3% annually, whereas among those who had used micronized 17 beta-estradiol, trabecular bone density response was inversely related to the dosage previously used. Additionally and independently, the level of calcium intake showed a statistically significant correlation with the change in spinal trabecular bone density (r = 0.37, p = 0.02). We conclude that micronized 17 beta-estradiol has a continuous skeletal dose-response effect in the range of 0.5 to 2.0 mg and that calcium intake positively modifies the skeletal response to 1.0 mg micronized 17 beta-estradiol.

  8. Estradiol enhances the acquisition of lithium chloride-induced conditioned taste aversion in castrated male rats

    NASA Astrophysics Data System (ADS)

    Lin, Shih-Fan; Tsai, Yuan-Feen; Tai, Mei-Yun; Yeh, Kuei-Ying

    2015-10-01

    The present study examined the effects of short-term treatment with ovarian hormones on the acquisition of conditioned taste aversion (CTA). Adult male rats were castrated and randomly divided into LiCl- and saline-treated groups. Nineteen days after castration, all of the animals were subjected to 23.5-h daily water deprivation for seven successive days (day 1 to day 7). On the conditioning day (day 8), the rats received either a 4 ml/kg of 0.15 M LiCl or the same dose of saline injection immediately after administration of a 2 % sucrose solution during the 30-min water session. Starting from day 6, rats in both groups received one of the following treatments: daily subcutaneous injection of (1) estradiol alone (30 μg/kg; estradiol benzoate (E) group), (2) estradiol plus progesterone (500 μg; E + progesterone (P) group), or (3) olive oil. From day 9 to day 11, all of the rats were given daily two-bottle preference tests during the 30-min fluid session. The estradiol and estradiol plus progesterone treatments in the LiCl groups resulted in significantly lower preference scores for the sucrose solution compared with the olive oil treatment groups, but no difference in preference score was seen between these two groups. These results indicate that both the estradiol and estradiol plus progesterone treatments in the LiCl groups enhanced the acquisition of CTA learning and suggest that estradiol affects the acquisition of CTA mediated by an activational effect in male rats, whereas progesterone treatment does not influence the effects of estradiol on the acquisition of CTA.

  9. The effects of estradiol and catecholestrogens on uterine glycogen metabolism in mink (Neovison vison)

    PubMed Central

    Rose, Jack; Hunt, Jason; Shelton, Jadd; Wyler, Steven; Mecham, Daniel

    2011-01-01

    Glycogen is a uterine histotroph nutrient synthesized by endometrial glands in response to estradiol. The effects of estradiol may be mediated, in part, through the catecholestrogens, 2-hydroxycatecholestradiol (2-OHE2) and 4-hydroxycatecholestradiol (4-OHE2), produced by hydroxylation of estradiol within the endometrium. Using ovariectomized mink, our objectives were to determine the effects of estradiol, 4-OHE2, and 2-OHE2 on uterine: 1) glycogen concentrations and tissue localization; 2) gene expression levels for glycogen synthase, glycogen phosphorylase, and glycogen synthase kinase-3B; and 3) protein expression levels for glycogen synthase kinase-3B (active) and phospho-glycogen synthase kinase-3B (inactive). Whole uterine glycogen concentrations (mean ± SEM, mg/g dry wt) were increased by estradiol (43.79 ± 5.35), 4-OHE2 (48.64 ± 4.02), and 2-OHE2 (41.36 ± 3.23) compared to controls (4.58 ± 1.16; P ≤ 0.05). Percent glycogen content of the glandular epithelia was three-fold greater than the luminal epithelia in response to estradiol and 4-OHE2 (P ≤ 0.05). Expression of glycogen synthase mRNA, the rate limiting enzyme in glycogen synthesis, was increased by 4-OHE2 and 2-OHE2 (P ≤ 0.05), but interestingly, was unaffected by estradiol. Expression of glycogen phosphorylase and glycogen synthase kinase-3B mRNAs were reduced by estradiol, 2-OHE2, and 4-OHE2 (P ≤ 0.05). Uterine phospho-glycogen synthase kinase-3B protein was barely detectable in control mink, whereas all three steroids increased phosphorylation and inactivation of the enzyme (P ≤ 0.05). We concluded that the effects of estradiol on uterine glycogen metabolism were mediated in part through catecholestrogens; perhaps the combined actions of these hormones are required for optimal uterine glycogen synthesis in mink. PMID:21196035

  10. Low doses of estradiol partly inhibit release of GH in sheep without affecting basal levels.

    PubMed

    Hudmon, A; Davenport, G; Coleman, E S; Sartin, J L

    2009-10-01

    Estradiol increases basal growth hormone (GH) concentrations in sheep and cattle. This study sought to determine the effects of estradiol on GH-releasing hormone (GRH)-stimulated GH release in sheep. Growth hormone secretory characteristics, the GH response to GRH, and steady-state GH mRNA concentrations were determined in castrated male lambs treated with 2 different doses of estradiol 17-beta for a 28-d experimental period. Although no differences between treatments in mean GH, basal GH, or GH pulse number were observed after 28 d of estradiol treatment, GH pulse amplitude was greater (P < 0.05) in the 2.00-cm implant-treated animals than in the control and 0.75-cm implant group. The effect of estradiol treatment on GRH-stimulated GH release revealed differences between the control and estradiol-treated animals (P < 0.05). The 15-min GH responses to 0.075 microg/kg hGRH in the control, 0.75-cm, and 2.00-cm implant groups, respectively, were 76 +/- 10, 22.6 +/- 2.1, and 43.6 +/- 15.0 ng/mL. Growth hormone mRNA content was determined for pituitary glands from the different treatment groups, and no differences in steady-state GH mRNA levels were observed. There were no differences in the mean plasma concentrations of IGF-I, cortisol, T(3), or T(4) from weekly samples. Growth hormone release from cultured ovine pituitary cells from control sheep was not affected by estradiol after 72 h or in a subsequent 3-h incubation with estradiol combined with GRH. These data suggest that estradiol has differing actions on basal and GRH-stimulated GH concentrations in plasma, but the increase in pulse amplitude does not represent an increased pituitary sensitivity to GRH. PMID:19616401

  11. Steady-state pharmacokinetics following application of a novel transdermal estradiol spray in healthy postmenopausal women.

    PubMed

    Morton, Terri L; Gattermeir, David J; Petersen, Craig A; Day, Wesley W; Schumacher, Robert J

    2009-09-01

    This study was designed to evaluate the steady-state pharmacokinetics (PK) of estradiol and its metabolites, estrone and estrone sulfate, following application of a novel estradiol transdermal spray to healthy postmenopausal women. Participants were randomly assigned in parallel to receive 1-, 2-, or 3-spray doses (24 participants/dose level) of a 1.7% estradiol metered-dose transdermal spray (1.53 mg/spray) once daily for 14 days. Blood was collected predose on days 1 to 14 and over 7 days after the last dose. Serum concentrations for all 3 analytes reached steady state by day 7 or 8 and were still slightly above baseline on day 21. Estradiol, estrone, and estrone sulfate serum concentrations generally increased with increasing dose. Mean estradiol and estrone maximum serum concentration (C(max)) following 1, 2, or 3 sprays for 14 days were 36 and 50, 57 and 60, and 54 and 71 pg/mL, respectively. Estradiol time when maximum concentration occurred (t(max)) was 18 to 20 hours. The area under the serum concentration-time curve over 24 hours following the last dose of study drug (AUC(0-24 h)) on day 14 for the 1-, 2-, and 3-spray groups, respectively, was 471, 736, and 742 pg.h/mL for estradiol; 886, 1208, and 1367 pg x h/mL for estrone; and 16,501, 26,515, and 27,971 pg x h/mL for estrone sulfate. The metered-dose estradiol transdermal spray delivers estradiol at therapeutic levels and produces low serum estrone concentrations. PMID:19628730

  12. Distribution and uptake of key polychlorinated biphenyl and polybrominated diphenyl ether congeners in benthic infauna relative to sediment organic enrichment.

    PubMed

    Burd, Brenda J; Macdonald, Tara A; Macdonald, Robie W; Ross, Peter S

    2014-10-01

    As part of a broader study of budgets, transport, and bioaccumulation of persistent organic contaminants in the Strait of Georgia, Canada, matching samples of sediment and bulk benthos were collected near two marine sewage outfalls, two large urban harbours, and background areas. Samples were analyzed for polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) congeners. We present data for those congeners that fell within the top six rankings by concentration (23 PCBs and 10 PBDEs) within at least one of the environmental media measured in other studies (air, water, sediments, benthos, pelagic biota). Multifactor regression analyses incorporating sediment characteristics (total organic carbon, fines) predicted uptake (r (2) = 0.74 to 0.98, p < 0.04) over the range of congeners and habitats examined. PBDEs were taken up by biota more readily than PCBs, suggesting a large, potentially available biological reservoir of PBDEs in sediments. Dominant congeners in benthos comprised PBDEs 47, 99, 209, and 100 and PCBs 138/163, 153, 101, 118, and 110. PBDE uptake was anomalously high near one wastewater outfall, likely due to selective feeding on PBDE-enriched particulates from that source. Conversely, outfalls supply food and sediments with PCB concentrations similar to ambient sediments. However, organic enrichment of sediments near outfalls clearly enhanced PCB uptake by benthos, probably due to greatly increased biomass turnover near these sources. Data suggest there to be an initial reservoir of PCBs in newly settled juvenile benthos, which is much less evident for PBDEs. This is likely a consequence of the ecosystem-wide distribution of legacy PCBs but not the more current-use PBDEs. Congener-uptake patterns were dependent on source and input dynamics, feeding methods, and contaminant metabolism or debromination, particularly of deca-BDE.

  13. Identification of indicator congeners and evaluation of emission pattern of polychlorinated naphthalenes in industrial stack gas emissions by statistical analyses.

    PubMed

    Liu, Guorui; Cai, Zongwei; Zheng, Minghui; Jiang, Xiaoxu; Nie, Zhiqiang; Wang, Mei

    2015-01-01

    Identifying marker congeners of unintentionally produced polychlorinated naphthalenes (PCNs) from industrial thermal sources might be useful for predicting total PCN (∑2-8PCN) emissions by the determination of only indicator congeners. In this study, potential indicator congeners were identified based on the PCN data in 122 stack gas samples from over 60 plants involved in more than ten industrial thermal sources reported in our previous case studies. Linear regression analyses identified that the concentrations of CN27/30, CN52/60, and CN66/67 correlated significantly with ∑2-8PCN (R(2)=0.77, 0.80, and 0.58, respectively; n=122, p<0.05), which might be good candidates for indicator congeners. Equations describing relationships between indicators and ∑2-8PCN were established. The linear regression analyses involving 122 samples showed that the relationships between the indicator congeners and ∑2-8PCN were not significantly affected by factors such as industry types, raw materials used, or operating conditions. Hierarchical cluster analysis and similarity calculations for the 122 stack gas samples were adopted to group those samples and evaluating their similarity and difference based on the PCN homolog distributions from different industrial thermal sources. Generally, the fractions of less chlorinated homologs comprised of di-, tri-, and tetra-homologs were much higher than that of more chlorinated homologs for up to 111 stack gas samples contained in group 1 and 2, which indicating the dominance of lower chlorinated homologs in stack gas from industrial thermal sources.

  14. Estimating the half-lives of PCB congeners in former capacitor workers measured over a 28-year interval.

    PubMed

    Seegal, Richard F; Fitzgerald, Edward F; Hills, Elaine A; Wolff, Mary S; Haase, Richard F; Todd, Andrew C; Parsons, Patrick; Molho, Eric S; Higgins, Donald S; Factor, Stewart A; Marek, Kenneth L; Seibyl, John P; Jennings, Danna L; McCaffrey, Robert J

    2011-01-01

    To date, most estimates of the half-life of polychlorinated biphenyls (PCBs) in humans have been based on relatively short follow-up periods. To address this issue, we determined the half-lives of PCB congeners of occupational origin in the serum of former capacitor workers as part of a study conducted in 2003-2006--approximately 28 years after their last occupational exposure. A total of 241 persons from a source population of 6798 former capacitor workers were interviewed and asked to donate a blood sample for serum PCB congener analysis. A subgroup of 45 participants also had serum archived from 1976 and reanalyzed for the same 27 PCB congeners by the same laboratory. Our estimates of the half-lives of the congeners among these 45 persons were longer than those reported by Wolff et al. (1992), due primarily to the much longer interval between exposure and determination of serum PCB concentrations. Half-lives were significantly greater for the heavy versus light occupational congeners, for women versus men and for those with low versus high initial exposure. Current serum total PCB concentrations, expressed as the geometric mean of wet weight data, averaged 6.7 ng/g for the entire 241-person cohort, which represents a 10-fold decrease from values reported in the late 1970s, but is still nearly twice the average for persons of similar age residing in the same area, but without occupational exposure. In addition, current serum PCB concentrations remained significantly and positively associated with earlier occupational exposure, but were not associated with fresh water fish consumption. In general, the results support a consistent and long-duration trend of increased PCB body burden in this cohort of former capacitor workers compared with non-occupationally exposed individuals. The results may aid in further understanding the toxicological/epidemiological consequences of exposure to PCBs in humans. PMID:20216575

  15. Polybrominated diphenyl ether congener patterns, hexabromocyclododecane, and brominated biphenyl 153 in eggs of peregrine falcons (Falco peregrinus) breeding in Sweden.

    PubMed

    Johansson, Anna-Karin; Sellström, Ulla; Lindberg, Peter; Bignert, Anders; De Witt, Cynthia A

    2009-01-01

    Previous analyses of 52 peregrine falcon (Falco peregrinus) eggs collected from two wild and one captive population in Sweden 1987 through 1999 were complemented by including additional polybrominated diphenyl ether (PBDE) congeners (BDE-35, -183, -184, -185, -196, -197, -203, and -207). In addition, 31 eggs not previously analyzed for hexabromocyclododecane (HBCD) and BDE-209 were analyzed for these. Geometric mean concentrations of BPBDEs, HBCD, and the hexabrominated biphenyl (BB-153) were 3,100, 140, and 81 ng/g of lipid weight for the southern population; 2,500, 110, and 84 ng/g of lipid weight for the northern population; and 47, not detected, and 8 ng/g of lipid weight for the captive population. The BDE congener pattern was dominated by BDE-153, -99, and -100. The results were used to investigate whether a difference in PBDE congener pattern could be distinguished between the two wild populations of peregrine falcons due to different diets, as the southern population preys mainly on birds belonging to the terrestrial food chain while the northern population preys more on aquatic birds. A multivariate t-test showed a subtle but significant (p < 0.001) difference in PBDE congener pattern between the two populations. However, our hypothesis that higher-brominated congeners of PBDEs would be present to a greater extent in the terrestrial food chain was not supported by principal component analysis. The average brood size for individual females from the southern population decreased with increasing concentrations of IPBDE in the eggs (log-linear regression p < 0.01).

  16. Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2.

    PubMed

    Jeffs, B; Negrin, C D; Graham, D; Clark, J S; Anderson, N H; Gauguier, D; Dominiczak, A F

    2000-01-01

    The identification of any quantitative trait locus (QTL) via a genome scan is only the first step toward the ultimate goal of gene identification. The next step is the production of congenic strains by which the existence of a QTL may be verified and the implicated chromosomal region be reduced to a size applicable to positional cloning of the causal gene. We used a speed congenic breeding protocol previously verified in mice for 2 blood pressure QTLs on rat chromosome 2. Four congenic strains were produced through introgression of various segments of chromosome 2 from Wistar-Kyoto rats from Glasgow colonies [WKY((Gla)) rats] into the recipient stroke-prone spontaneously hypertensive rats from Glasgow colonies [SHRSP((Gla))], and vice versa. The number of backcross generations required for each strain to achieve complete homozygosity at 83 background genetic markers in a "best" male varied between 3 and 4. Transfer of the region of rat chromosome 2 containing both QTLs from WKY((Gla)) into an SHRSP((Gla)) genetic background lowered both baseline and salt-loaded systolic blood pressure by approximately 20 and approximately 40 mm Hg in male congenic rats compared with the SHRSP parental strain (F=53.4, P<0.005; F=28.0, P< 0.0005, respectively). In contrast, control animals for stowaway heterozygosity presented no deviation from the blood pressure values recorded for the SHRSP((Gla)), indicating that if such heterozygosity exists, its effect on blood pressure is negligible. A reciprocal strategy in which 1 or both QTLs on rat chromosome 2 were transferred from SHRSP((Gla)) into a WKY((Gla)) genetic background resulted in statistically significant but smaller blood pressure increases for 1 of these QTLs. These results confirm the existence of blood pressure QTLs on rat chromosome 2 and demonstrate the applicability of a speed congenic strategy in the rat and emphasize the important role of the genetic background.

  17. Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation.

    PubMed

    de Resende, Micheline M; Amaral, Sandra L; Moreno, Carol; Greene, Andrew S

    2008-03-14

    Previous studies have indicated the importance of angiotensin II (ANG II) in skeletal muscle angiogenesis. The present study explored the effect of regulation of the renin gene on angiogenesis induced by electrical stimulation with the use of physiological, pharmacological, and genetic manipulations of the renin-angiotensin system (RAS). Transfer of the entire chromosome 13, containing the physiologically regulated renin gene, from the normotensive inbred Brown Norway (BN) rat into the background of an inbred substrain of the Dahl salt-sensitive (SS/Mcwi) rat restored renin levels and the angiogenic response after electrical stimulation. This restored response was significantly attenuated when SS-13(BN)/Mcwi consomic rats were treated with lisinopril or high-salt diet. The role of ANG II on this effect was confirmed by the complete restoration of skeletal muscle angiogenesis in SS/Mcwi rats infused with subpressor doses of ANG II. Congenic strains derived from the SS-13(BN)/Mcwi consomic were used to further verify the role of the renin gene in this response. Microvessel density was markedly increased after stimulation in congenic strains that contained the renin gene from the BN rat (congenic lines A and D). This angiogenic response was suppressed in control strains that carried regions of the BN genome just above (congenic line C) or just below (congenic line B) the renin gene. The present study emphasizes the importance of maintaining normal renin regulation as well as ANG II levels during the angiogenesis process with a combination of physiological, genetic, and pharmacological manipulation of the RAS. PMID:18198281

  18. A metabolomics study of the inhibitory effect of 17-beta-estradiol on osteoclast proliferation and differentiation.

    PubMed

    Liu, Xiaoyan; Liu, Yanqiu; Cheng, Mengchun; Zhang, Xiaozhe; Xiao, Hongbin

    2015-02-01

    Estradiol is a major drug used clinically to alleviate osteoporosis, partly through inhibition of the activity of osteoclasts, which play a crucial role in bone resorption. So far, little is known about the effects of estradiol on osteoclast metabolism. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC/MS)-based metabolomics strategy was used to investigate the metabolite response to 17β-estradiol in mouse osteoclast RAW264.7, a commonly used cell model for studying osteoporosis. Our results showed that the application of estradiol altered the levels of 27 intracellular metabolites, including lysophosphatidylcholines (LysoPCs), other lipids and amino acid derivants. The changes of all the 27 metabolites were observed in the study of estradiol induced osteoclast proliferation inhibition (1 μM estradiol applied), while the changes of only 18 metabolites were observed in the study of differentiation inhibition (0.1 μM estradiol applied). Further pathway impact analysis determined glycerophospholipid metabolism as the main potential target pathway of estradiol, which was further confirmed by LCAT (phosphatidylcholine-sterol acyltransferase) activity changes and lipid peroxidative product (MDA, methane dicarboxylic aldehyde) changes caused by estradiol. Additionally, we found that estradiol significantly decreased intracellular oxidative stress during cell proliferation but not during cell differentiation. Our study suggested that estradiol generated a highly condition-dependent influence on osteoclast metabolism.

  19. A metabolomics study of the inhibitory effect of 17-beta-estradiol on osteoclast proliferation and differentiation.

    PubMed

    Liu, Xiaoyan; Liu, Yanqiu; Cheng, Mengchun; Zhang, Xiaozhe; Xiao, Hongbin

    2015-02-01

    Estradiol is a major drug used clinically to alleviate osteoporosis, partly through inhibition of the activity of osteoclasts, which play a crucial role in bone resorption. So far, little is known about the effects of estradiol on osteoclast metabolism. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC/MS)-based metabolomics strategy was used to investigate the metabolite response to 17β-estradiol in mouse osteoclast RAW264.7, a commonly used cell model for studying osteoporosis. Our results showed that the application of estradiol altered the levels of 27 intracellular metabolites, including lysophosphatidylcholines (LysoPCs), other lipids and amino acid derivants. The changes of all the 27 metabolites were observed in the study of estradiol induced osteoclast proliferation inhibition (1 μM estradiol applied), while the changes of only 18 metabolites were observed in the study of differentiation inhibition (0.1 μM estradiol applied). Further pathway impact analysis determined glycerophospholipid metabolism as the main potential target pathway of estradiol, which was further confirmed by LCAT (phosphatidylcholine-sterol acyltransferase) activity changes and lipid peroxidative product (MDA, methane dicarboxylic aldehyde) changes caused by estradiol. Additionally, we found that estradiol significantly decreased intracellular oxidative stress during cell proliferation but not during cell differentiation. Our study suggested that estradiol generated a highly condition-dependent influence on osteoclast metabolism. PMID:25474166

  20. Gonadotropin and estradiol secretion during the week of placebo therapy in oral contraceptive pill users.

    PubMed

    van der Spuy, Z M; Sohnius, U; Pienaar, C A; Schall, R

    1990-12-01

    The changes in the hypothalamic-pituitary-ovarian axis during the placebo week in oral contraceptive pill users were assessed. Fifteen women using the combined oral contraceptive pill were studied for eight hours at the start and at the end of the placebo week and gonadotropin secretion and estradiol concentrations were compared with those in control women in the follicular phase of an unmedicated menstrual cycle. Both gonadotropin and estradiol concentrations were suppressed at the start of the placebo week. By day 7 of placebo, gonadotropin concentrations and pulse patterns were indistinguishable from those of the control subjects although estradiol concentrations were still significantly lower.

  1. Mechanism of the Rapid Effect of 17β -Estradiol on Medial Amygdala Neurons

    NASA Astrophysics Data System (ADS)

    Nabekura, Junichi; Oomura, Yutaka; Minami, Taketsugu; Mizuno, Yuji; Fukuda, Atsuo

    1986-07-01

    The mechanism by which sex steroids rapidly modulate the excitability of neurons was investigated by intracellular recording of neurons in rat medial amygdala brain slices. Brief hyperpolarization and increased potassium conductance were produced by 17β - estradiol. This effect persisted after elimination of synaptic input and after suppression of protein synthesis. Thus, 17β -estradiol directly changes the ionic conductance of the postsynaptic membrane of medial amygdala neurons. In addition, a greater proportion of the neurons from females than from males responded to 17β -estradiol.

  2. Determination of estradiol valerate in pharmaceutical preparations and human serum by flow injection chemiluminescence.

    PubMed

    Liu, Wenwen; Xie, Liangxiao; Liu, Hongshuang; Xu, Shichao; Hu, Bingcheng; Cao, Wei

    2013-01-01

    A novel method for the detection of trace estradiol valerate (EV) in pharmaceutical preparations and human serum was developed by inhibition of luminol chemiluminescence (CL) by estradiol valerate on the zinc deuteroporphyrin (ZnDP)-enhanced luminol-K3 Fe(CN)6 chemiluminescence system. Under optimized experimental conditions, CL intensity and concentration of estradiol valerate had a good linear relationship in the ranges of 8.0 × 10(-8) to 1.0 × 10(-5) g/mL. Detection limit (3σ) was estimated to be 3.5 × 10(-8) g/mL. The proposed method was applied successfully for the determination of estradiol valerate in pharmaceutical preparations and human serum and recoveries were 97.0-105.0% and 95.5-106.0%, respectively. The possible mechanism of the CL system is discussed.

  3. OOCYTE ENVELOPE PROTEINS AND VITELLOGENIN IN MALE SHEEPHEAD MINNOW EXPOSED TO ESTRADIOL

    EPA Science Inventory

    Oocyte Envelope Proteins and Vitellogenin Expression in Male Sheepshead Minnows Exposed to Estradiol (Abstract). To be presented at the 22nd Annual Meeting of the Society of Environmental Toxicology and Chemistry: Changing Environmental Awareness: Societal Concerns and Scientifi...

  4. COULD ETHINYL ESTRADIOL AFFECT THE POPULATION BIOLOGY OF CUNNER, TAUTOGOLABRUS ADSPERSUS

    EPA Science Inventory

    Endocrine disrupting chemicals in the environment may disturb the population dynamics of wildlife by affecting reproductive output and embryonic development of organisms. This study used a population model to evaluate whether ethinyl estradiol (EE2 could affect cunner Tautogolabr...

  5. Chemometric comparison of polychlorinated biphenyl residues and toxicologically active polychlorinated biphenyl congeners in the eggs of Forster's Terns (Sterna fosteri)

    USGS Publications Warehouse

    Schwartz, Ted R.; Stalling, David L.

    1991-01-01

    The separation and characterization of complex mixtures of polychlorinated biphenyls (PCBs) is approached from the perspective of a problem in chemometrics. A technique for quantitative determination of PCB congeners is described as well as an enrichment technique designed to isolate only those congener residues which induce mixed aryl hydrocarbon hydroxylase enzyme activity. A congener-specific procedure is utilized for the determination of PCBs in whichn-alkyl trichloroacetates are used as retention index marker compounds. Retention indices are reproducible in the range of ±0.05 to ±0.7 depending on the specific congener. A laboratory data base system developed to aid in the editing and quantitation of data generated from capillary gas chromatography was employed to quantitate chromatographic data. Data base management was provided by computer programs written in VAX-DSM (Digital Standard MUMPS) for the VAX-DEC (Digital Equipment Corp.) family of computers.In the chemometric evaluation of these complex chromatographic profiles, data are viewed from a single analysis as a point in multi-dimensional space. Principal Components Analysis was used to obtain a representation of the data in a lower dimensional space. Two-and three-dimensional proections based on sample scores from the principal components models were used to visualize the behavior of Aroclor® mixtures. These models can be used to determine if new sample profiles may be represented by Aroclor profiles. Concentrations of individual congeners of a given chlorine substitution may be summed to form homologue concentration. However, the use of homologue concentrations in classification studies with environmental samples can lead to erroneous conclusions about sample similarity. Chemometric applications are discussed for evaluation of Aroclor mixture analysis and compositional description of environmental residues of PCBs in eggs of Forster's terns (Sterna fosteri) collected from colonies near Lake Poygan

  6. Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

    SciTech Connect

    Muthukumaran, Padmalosini; Lim, Chwee Teck; Lee, Taeyong

    2012-07-06

    Highlights: Black-Right-Pointing-Pointer Estradiol induced stiffness changes of osteoblasts were quantified using AFM. Black-Right-Pointing-Pointer Estradiol causes significant decrease in the stiffness of osteoblasts. Black-Right-Pointing-Pointer Decreased stiffness was caused by decreased density of f-actin network. Black-Right-Pointing-Pointer Stiffness changes were not associated with mineralized matrix of osteoblasts. Black-Right-Pointing-Pointer Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E{sup Asterisk-Operator }) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with {beta}-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E{sup Asterisk-Operator }. The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E{sup Asterisk-Operator} of osteoblasts significantly decreased by 43-46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness

  7. Sorption behaviors of a persistent toxaphene congener on marine sediments under different physicochemical conditions.

    PubMed

    Soubaneh, Youssouf Djibril; Gagné, Jean-Pierre; Lebeuf, Michel; Gouteux, Bruno; Nikiforov, Vladimir; Awaleh, Mohamed Osman

    2014-11-01

    Sorptive processes are important parameters affecting the mobility, availability and fate of persistent organic pollutants (POPs), such as toxaphene, in aquatic systems. The sorption and desorption behaviors of the B7-1450, a stable toxaphene congener in environment, on marine sediment was studied under different temperature and salinity conditions to better understand the B-1450 distribution in estuarine systems. The data were fitted to different sorption models to characterize sorption behaviors by evaluating sorption coefficients and sequestrated fraction of B7-1450 on sediments. High carbon-normalized sorption coefficients (Koc) of the B7-1450 were observed with values ranging from 3.2×104 to 6.0×104 mL g(-1) under experimental conditions. The data showed an increase of B7-1450 sorption coefficients with the salinity and a decrease with temperature. These investigations indicate that B7-1450 is three times more sequestred on sediments in cold (2°C, 30 psu) than in warm marine conditions (20°C, 30 psu). These results suggest that the mobility and bioavailable of B7-1450 or other POPs from the sediments could be less important in cold marine comparatively in warm marine and warm freshwater media. As a result of climate changes, the warming of mid and high latitudes coastal waters could enhance the mobility of POPs.

  8. Detailed analysis of polybrominated biphenyl congeners in bird eggs from Norway.

    PubMed

    Vetter, Walter; von der Recke, Roland; Herzke, Dorte; Nygård, Torgeir

    2008-12-01

    Individual eggs of six species of birds from Norway representing different food chains were analysed for residues of polybrominated biphenyls (PBBs). In all species, the residue pattern was dominated by hexaBBs. The dominating congeners were PBB 153, PBB 154, and PBB 155. Whereas PBB 153 is present in technical hexabromobiphenyl, PBB 154 and PBB 155 are formed by the reductive debromination of decabromobiphenyl. This was evidenced by the detection of several heptaBBs and octaBBs all of which are typical degradation intermediates of PBB 209. Hepta- and octaBBs were more than one order of magnitude less abundant than the hexaBBs. The second most prevailing homologue group was pentaBBs. The most relevant pentabrominated isomers were PBB 99 and PBB 101. Concentrations of the three hexaBBs--PBB 153, PBB 154, and PBB 155--amounted to 1.3-13 ng/g wet weight or 3-23% of the contamination with polybrominated diphenyl ethers. PMID:18472199

  9. Concentrations of polychlorinated biphenyl congeners in cultivated oysters (Crassostrea gigas) in western Taiwan.

    PubMed

    Fang, M D; Fang, H-T; Lee, C-L; Ko, F-C; Baker, J E

    2006-08-01

    Spatial and temporal variations of polychlorinated biphenyl (PCB) concentrations in cultivated oysters from five aquaculture areas along the western coast of Taiwan were investigated. Poor correlations between total PCB concentrations (ng/g dry weight [dw]) and physiologic parameters of oysters (shell length, width, thickness, and lipid content) were found. Total PCB concentrations ranged from 3.4 to 94 cng/g dw. The highest value was found in oysters from the Lu'ermen aquaculture area, which receives wastewater from a sodium hydroxide and pentachlorophenol factory. Furthermore, principal component analysis confirmed that the PCB congener pattern in this area was distinct from others and that two additional pollution sources might exist in the Tainan and Hsinchu areas. Oysters with PCB concentrations > 1 SD above the geometric mean were found mainly in Tainan (stations TN5 to TN9) with only one increased concentration in the Yunlin (station YL2) and Hsinchu (station HC4) aquaculture areas. Except for four confined stations, TN3 to TN6, where total PCB concentrations were higher (p = 0.028) in the warmer (May and July) than in the colder season (November and March), seasonal variation of total PCB concentrations in oysters was not significant. Geometric mean and geometric mean plus 1 SD of total PCB concentrations in this study are lower than those in South Korea and the United States (Mussel Watch). PMID:16583259

  10. Hydrocortisone-induced embryotoxicity and embryonic drug disposition in H-2 congenic mice

    SciTech Connect

    Roberts, L.S.G.

    1986-01-01

    Congenic mouse strains C57BL/10Sn (B10) and B10.A/SgSn(B10A), genetically different only at the H-2 complex, were compared for sensitivity to glucocorticoid-induced embryotoxicity and embryonic drug disposition. B10A mice dosed intramuscularly with 0, 100, 150 and 200 mg hydrocortisone/kg body weight on gestational day twelve, and B10 mice injected with 0, 200, 400, 600, and 800 mg/kg, were evaluated at dissection on gestational day eighteen for signs of toxicity. In both strains, probit analysis of cleft palate production demonstrated a linear dose response. The ED50 for cleft palate production demonstrates a linear dose response. The ED50 for cleft palate production in B10A mice was 143.6 mg/kg and 512.0 mg/kg for the B10 strain. Embryonic exposure was evaluated by administration of /sup 3/H-hydrocortisone (5 uCi/mouse) to pregnant mice on day twelve of gestation, at the ED50 for cleft palate production in B10A strain. The purposes of the experiment were to quantify the difference in susceptibility to steroid-induced cleft palate, determine if a milder manifestation of embryotoxicity, fetal growth retardation, occurred at sub-clefting dosages, and determine if the difference in sensitivity to hydrocortisone-induced embryotoxicity was the result of an underlying difference in embryonic exposure to the teratogen.

  11. Gas chromatographic determination of volatile congeners in spirit drinks: interlaboratory study.

    PubMed

    Kelly, J; Chapman, S; Brereton, P; Bertrand, A; Guillou, C; Wittkowski, R

    1999-01-01

    An interlaboratory study of a gas chromatographic (GC) method for the determination of volatile congeners in spirit drinks was conducted; 31 laboratories from 8 countries took part in the study. The method uses GC with flame ionization detection and incorporates several quality control measures which permit the choice of chromatographic system and conditions to be selected by the user. Spirit drink samples were prepared and sent to participants as 10 blind duplicate or split-level test materials for the determination of 1,1-diethoxyethane (acetal), 2-methylbutan-1-ol (active amyl alcohol), 3-methylbutan-1-ol (isoamyl alcohol), methanol (methyl alcohol), ethyl ethanoate (ethyl acetate), butan-1-ol (n-butanol), butan-2-ol (sec-butanol), 2-methylpropan-1-ol (isobutyl alcohol), propan-1-ol (n-propanol), and ethanal (acetaldehyde). The precision of the method for 9 of the 10 analytes was well within the range predicted by the Horwitz equation. The precision of the most volatile analyte, ethanal, was just above statistically predicted levels. This method is recommended for official regulatory purposes. PMID:10589492

  12. Chlorinated paraffins in indoor air and dust: concentrations, congener patterns, and human exposure.

    PubMed

    Fridén, Ulrika E; McLachlan, Michael S; Berger, Urs

    2011-10-01

    Chlorinated paraffins (CPs) are large production volume chemicals used in a wide variety of commercial applications. They are ubiquitous in the environment and humans. Human exposure via the indoor environment has, however, been barely investigated. In the present study 44 indoor air and six dust samples from apartments in Stockholm, Sweden, were analyzed for CPs, and indoor air concentrations are reported for the first time. The sumCP concentration (short chain CPs (SCCPs) and medium chain CPs (MCCPs)) in air ranged from <5-210 ng m(-3) as quantified by gas chromatography coupled to electron ionization tandem mass spectrometry (GC/EI-MS/MS). Congener group patterns were studied using GC with electron capture negative ionization MS (GC/ECNI-MS). The air samples were dominated by the more volatile SCCPs compared to MCCPs. SumCPs were quantified by GC/EI-MS/MS in the dust samples at low μg g(-1) levels, with a chromatographic pattern suggesting the prevalence of longer chain CPs compared to air. The median exposure to sumCPs via the indoor environment was estimated to be ~1 μg day(-1) for both adults and toddlers. Adult exposure was dominated by inhalation, while dust ingestion was suggested to be more important for toddlers. Comparing these results to literature data on dietary intake indicates that human exposure to CPs from the indoor environment is not negligible. PMID:21612825

  13. Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans.

    PubMed

    Ahmad, Aijaz; Wani, Mohmmad Younus; Khan, Amber; Manzoor, Nikhat; Molepo, Julitha

    2015-01-01

    We previously reported the antifungal properties of a monoterpene phenol "Eugenol" against different Candida strains and have observed that the addition of methyl group to eugenol drastically increased its antimicrobial potency. Based on the results and the importance of medicinal synthetic chemistry, we synthesized eugenol-tosylate and its congeners (E1-E6) and tested their antifungal activity against different clinical fluconazole (FLC)- susceptible and FLC- resistant C. albicans isolates alone and in combination with FLC by determining fractional inhibitory concentration indices (FICIs) and isobolograms calculated from microdilution assays. Minimum inhibitory concentration (MIC) results confirmed that all the tested C. albicans strains were variably susceptible to the semi-synthetic derivatives E1-E6, with MIC values ranging from 1-62 μg/ml. The test compounds in combination with FLC exhibited either synergy (36%), additive (41%) or indifferent (23%) interactions, however, no antagonistic interactions were observed. The MICs of FLC decreased 2-9 fold when used in combination with the test compounds. Like their precursor eugenol, all the derivatives showed significant impairment of ergosterol biosynthesis in all C. albicans strains coupled with down regulation of the important ergosterol biosynthesis pathway gene-ERG11. The results were further validated by docking studies, which revealed that the inhibitors snugly fitting the active site of the target enzyme, mimicking fluconazole, may well explain their excellent inhibitory activity. Our results suggest that these compounds have a great potential as antifungals, which can be used as chemosensitizing agents with the known antifungal drugs.

  14. Neuroactive Multifunctional Tacrine Congeners with Cholinesterase, Anti-Amyloid Aggregation and Neuroprotective Properties

    PubMed Central

    Kozurkova, Maria; Hamulakova, Slavka; Gazova, Zuzana; Paulikova, Helena; Kristian, Pavol

    2011-01-01

    The review summarizes research into the highly relevant topics of cholinesterase and amyloid aggregation inhibitors connected to tacrine congeners, both of which are associated with neurogenerative diseases. Various opinions will be discussed regarding the dual binding site inhibitors which are characterized by increased inhibitor potency against acetylcholin/butyrylcholine esterase and amyloid formation. It is suggested that these compounds can both raise levels of acetylcholine by binding to the active site, and also prevent amyloid aggregation. In connection with this problem, the mono/dual binding of the multifunctional derivatives of tacrine, their mode of action and their neuroprotective activities are reported. The influence of low molecular compounds on protein amyloid aggregation, which might be considered as a potential therapeutic strategy in the treatment of Alzheimer's disease is also reported. Finally, attention is paid to some physico-chemical factors, such as desolvation energies describing the transfer of the substrate solvated by water, the metal-chelating properties of biometals reacting with amyloid precursor protein, amyloid beta peptide and tau protein.

  15. Dioxins and congener-specific polychlorinated biphenyls in three avian species from the Wisconsin River, Wisconsin

    USGS Publications Warehouse

    Custer, T.W.; Custer, Christine M.; Hines, Randy K.

    2002-01-01

    Sediments from the Wisconsin River, WI, USA are contaminated with 2,3,7,8-tetrachloro-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs). Wet weight concentrations of TCDD and PCBs in eggs were at background levels and highest in the piscivorous hooded merganser (Lophodytes cucullatus; geometric MEAN=7 pg/g TCDD and 0.92 I?g/g PCBs) and lowest in the omnivorous wood duck (Aix sponsa) (<1 pg/g and 0.07 I?g/g); concentrations in eggs of the insectivorous tree swallow (Tachycineta bicolor) were intermediate (<1 pg/g and 0.33 I?g/g). Positive accumulation rates of TCDD (8a??19 pg/day) and PCBs (0.4a??0.7 I?g/day) in tree swallow nestlings suggest that the Wisconsin River is the source of these contaminants for tree swallow nestlings. The lower representation of trichlorobiphenyls and tetrachorobiphenyls in hooded merganser eggs compared to wood duck or tree swallow eggs suggests that the hooded merganser or its diet has a greater ability to metabolize lower-numbered PCB congeners than wood ducks or tree swallows.

  16. Introduced and native congeners use different resource allocation strategies to maintain performance during infection.

    PubMed

    Coon, Courtney A C; Brace, Amber J; McWilliams, Scott R; McCue, Marshall D; Martin, Lynn B

    2014-01-01

    Abstract Hosts can manage parasitic infections using an array of tactics, which are likely to vary contingent on coevolutionary history between the host and the parasite. Here we asked whether coping ability of congeners that differ in host-parasite coevolutionary history differed in response to experimental infections with a coccidian parasite. House sparrows (Passer domesticus) and gray-headed sparrows (Passer griseus) are sympatric and ecologically similar, but house sparrows are recent colonizers of Kenya, the site of our comparison, whereas gray-headed sparrows are native. We evaluated three variables as barometers of infection coping ability: vertical flight, pectoral muscle size, and fat score. We also measured routing of a dose of (13)C-labeled leucine, an essential amino acid, among tissues to compare resource allocation strategies in response to infection. We found that burden effects on performance were minimal in both species, but house sparrows maintained considerably higher burdens than gray-headed sparrows regardless of exposure. House sparrows also had more exogeneous leucine tracer in all tissues after 24 h, demonstrating a difference in the way the two species allocate or distribute resources. We argue that house sparrows may be maintaining larger resource reserves to mitigate costs associated with exposure and infection. Additionally, in response to increased parasite exposure, gray-headed sparrows had less leucine tracer in their spleens and more in their gonads, whereas house sparrows did not change allocation, perhaps indicating a trade-off that is not experienced by the introduced species.

  17. Oviposition by Aedes aegypti and Aedes albopictus: influence of congeners and of oviposition site characteristics.

    PubMed

    Rey, Jorge R; O'Connell, Sheila M

    2014-06-01

    We investigated the oviposition behavior of Ae. aegypti and Ae. albopictus. In particular we examined whether small-scale site characteristics and the presence of conspecifics or congeners altered oviposition by these mosquitoes. Various combinations of females of the two species were allowed to oviposit inside cages among either vegetation (potted plants) or structural components (wood and concrete blocks). Numbers of eggs deposited per female were compared between species, sides, and treatments. Most significant differences between treatments and species involved differences between single species and mixed species treatments. Ae. aegypti deposited more eggs/female in the vegetation side than in the structure side whereas the opposite pattern was evident for Ae. albopictus. Ae. aegypti females had higher frequency of skip oviposition than Ae. albopictus. An average of 63% of the containers in the two-species treatments contained eggs of both species, with more frequent joint occurrences observed in the treatment with three females of each species than in the treatments with one of each. Our results point to the existence of various interactions between gravid Ae. aegypti and Ae. albopictus females at or near the oviposition sites but further experimental work is necessary to fully characterize the interactions and their specific mechanisms.

  18. A genome-wide panel of congenic mice reveals widespread epistasis of behavior quantitative trait loci.

    PubMed

    Gale, G D; Yazdi, R D; Khan, A H; Lusis, A J; Davis, R C; Smith, D J

    2009-06-01

    Understanding the genetics of behavioral variation remains a fascinating but difficult problem with considerable theoretical and practical implications. We used the genome-tagged mice (GTM) and an extensive test battery of well-validated behavioral assays to scan the genome for behavioral quantitative trait loci (QTLs). The GTM are a panel of 'speed congenic' mice consisting of over 60 strains spanning the entire autosomal genome. Each strain harbors a small (approximately 23 cM) DBA/2J donor segment on a uniform C57BL/6J background. The panel allows for mapping to regions as small as 5 cM and provides a powerful new tool for increasing mapping power and replicability in the analysis of QTLs. A total of 97 loci were mapped for a variety of complex behavioral traits including hyperactivity, anxiety, prepulse inhibition, avoidance and conditional fear. A larger number of loci were recovered than generally attained from standard mapping crosses. In addition, a surprisingly high proportion of loci, 63%, showed phenotypes unlike either of the parental strains. These data suggest that epistasis decreases sensitivity of locus detection in traditional crosses and demonstrate the utility of the GTM for mapping complex behavioral traits with high sensitivity and precision.

  19. Concentrations of polychlorinated biphenyl congeners in cultivated oysters (Crassostrea gigas) in western Taiwan.

    PubMed

    Fang, M D; Fang, H-T; Lee, C-L; Ko, F-C; Baker, J E

    2006-08-01

    Spatial and temporal variations of polychlorinated biphenyl (PCB) concentrations in cultivated oysters from five aquaculture areas along the western coast of Taiwan were investigated. Poor correlations between total PCB concentrations (ng/g dry weight [dw]) and physiologic parameters of oysters (shell length, width, thickness, and lipid content) were found. Total PCB concentrations ranged from 3.4 to 94 cng/g dw. The highest value was found in oysters from the Lu'ermen aquaculture area, which receives wastewater from a sodium hydroxide and pentachlorophenol factory. Furthermore, principal component analysis confirmed that the PCB congener pattern in this area was distinct from others and that two additional pollution sources might exist in the Tainan and Hsinchu areas. Oysters with PCB concentrations > 1 SD above the geometric mean were found mainly in Tainan (stations TN5 to TN9) with only one increased concentration in the Yunlin (station YL2) and Hsinchu (station HC4) aquaculture areas. Except for four confined stations, TN3 to TN6, where total PCB concentrations were higher (p = 0.028) in the warmer (May and July) than in the colder season (November and March), seasonal variation of total PCB concentrations in oysters was not significant. Geometric mean and geometric mean plus 1 SD of total PCB concentrations in this study are lower than those in South Korea and the United States (Mussel Watch).

  20. The hemodynamic effects of ibopamine, a dopamine congener, in patients with congestive heart failure.

    PubMed

    Leier, C V; Ren, J H; Huss, P; Unverferth, D V

    1986-01-01

    Ten patients with congestive heart failure underwent noninvasive and invasive hemodynamic testing before and sequentially after the administration of ibopamine to determine the cardiovascular effects of this oral dopamine congener. Single doses of 200, 400 and 600 mg were administered to all patients and 5 repeated doses of 200 or 400 mg were studied in 8. Hemodynamic effects occurred as early as 30 minutes and lasted up to 4 hours after dosing. In general, ibopamine elicited statistically significant dose-related increases in cardiac output and reductions in the derived resistance of the systemic and pulmonary circulations. A biphasic response in central and peripheral pressures was observed; up to 1 hour after administration, ibopamine elevated mean right and left atrial pressures and pulmonary and systemic arterial pressures with a significant reduction of these measurements beyond 1 hour. It did not alter heart rate. Repeated doses qualitatively affected hemodynamics similar to the initial dose and did not appear to be accompanied by short-term tolerance. While oral ibopamine elicits some favorable hemodynamic effects in humans with cardiac failure, the biphasic hemodynamic response is generally undesirable in the majority of these patients.

  1. Oviposition by Aedes aegypti and Aedes albopictus: influence of congeners and of oviposition site characteristics.

    PubMed

    Rey, Jorge R; O'Connell, Sheila M

    2014-06-01

    We investigated the oviposition behavior of Ae. aegypti and Ae. albopictus. In particular we examined whether small-scale site characteristics and the presence of conspecifics or congeners altered oviposition by these mosquitoes. Various combinations of females of the two species were allowed to oviposit inside cages among either vegetation (potted plants) or structural components (wood and concrete blocks). Numbers of eggs deposited per female were compared between species, sides, and treatments. Most significant differences between treatments and species involved differences between single species and mixed species treatments. Ae. aegypti deposited more eggs/female in the vegetation side than in the structure side whereas the opposite pattern was evident for Ae. albopictus. Ae. aegypti females had higher frequency of skip oviposition than Ae. albopictus. An average of 63% of the containers in the two-species treatments contained eggs of both species, with more frequent joint occurrences observed in the treatment with three females of each species than in the treatments with one of each. Our results point to the existence of various interactions between gravid Ae. aegypti and Ae. albopictus females at or near the oviposition sites but further experimental work is necessary to fully characterize the interactions and their specific mechanisms. PMID:24820572

  2. Sorption behaviors of a persistent toxaphene congener on marine sediments under different physicochemical conditions.

    PubMed

    Soubaneh, Youssouf Djibril; Gagné, Jean-Pierre; Lebeuf, Michel; Gouteux, Bruno; Nikiforov, Vladimir; Awaleh, Mohamed Osman

    2014-11-01

    Sorptive processes are important parameters affecting the mobility, availability and fate of persistent organic pollutants (POPs), such as toxaphene, in aquatic systems. The sorption and desorption behaviors of the B7-1450, a stable toxaphene congener in environment, on marine sediment was studied under different temperature and salinity conditions to better understand the B-1450 distribution in estuarine systems. The data were fitted to different sorption models to characterize sorption behaviors by evaluating sorption coefficients and sequestrated fraction of B7-1450 on sediments. High carbon-normalized sorption coefficients (Koc) of the B7-1450 were observed with values ranging from 3.2×104 to 6.0×104 mL g(-1) under experimental conditions. The data showed an increase of B7-1450 sorption coefficients with the salinity and a decrease with temperature. These investigations indicate that B7-1450 is three times more sequestred on sediments in cold (2°C, 30 psu) than in warm marine conditions (20°C, 30 psu). These results suggest that the mobility and bioavailable of B7-1450 or other POPs from the sediments could be less important in cold marine comparatively in warm marine and warm freshwater media. As a result of climate changes, the warming of mid and high latitudes coastal waters could enhance the mobility of POPs. PMID:25113217

  3. Foodchain bioaccumulation patterns of pesticides, PCB isomers and dioxin/furan congeners in the Great Lakes

    SciTech Connect

    Whittle, D.M.; Kiriluk, R.M.; Carswell, A.; Keir, M.J.

    1994-12-31

    Lake Ontario is one of the most contaminated Great Lakes. A detailed analysis of whole body concentrations of organic contaminants was conducted on a simple 4 compartment coldwater foodchain consisting of 7 species including several invertebrate diet items, prey fish species and the top predator lake trout. Sediment samples from the same site were analyzed for a similar suite of contaminants. Analyses were performed using a combination of HRMS/MS and GC/MS. All concentrations were reported on a whole animal wet weight basis and lipid weight concentrations. Total Toxic Equivalent Factors (TEFS) were calculated for both dioxin and furan isomers and coplanar PCBs. PCB 110 (pentachlorobiphenyl) was the dominant congener in sediment samples as well as samples of benthic invertebrates. On the other hand, PCB 138 and 153 (hexachlorobiphenyls) were found at the highest concentration in the top predator lake trout and a prey species that feeds primarily in the water column. Mysis relicta, a zooplankton species that migrates diurnally through the water column, had similar levels of both PCB 110 and PCB 138/153. PCB 77 was consistently the highest coplanar PCB found in all samples. In all biological samples analyzed 2,3,7,8 substituted tetrachlorodioxin and furan isomers were consistently found at the highest levels. Lipid normalization of all whole body data did not significantly change the bioaccumulation factors calculated using wet weight concentrations.

  4. Levels and congener profiles of PCDD/Fs, PCBs and PBDEs in seafood from China.

    PubMed

    Shen, Haitao; Yu, Cun; Ying, Ying; Zhao, Yunfeng; Wu, Yongning; Han, Jianlong; Xu, Qingyuan

    2009-11-01

    A nationwide investigation into polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) in market seafood was conducted for the first time in this study. Total PCDD/F concentrations in fatty fish ranged from 0.13 to 8.64 pg g(-1) wet weight (mean 2.05 pg g(-1) wet weight), total PCB concentrations ranged from 38.9 to 3514 pg g(-1) wet weight (mean 1133 pg g(-1) wet weight), and total PBDE concentrations ranged from 42.8 to 913 pg g(-1) wet weight (mean 322 pg g(-1) wet weight). Corresponding mean toxicity equivalent (TEQ) values for total PCDD/F and dioxin-like PCB were 0.25 pg g(-1) wet weight (WHO 98-TEQ) and 0.32 pg g(-1) wet weight (WHO 98-TEQ), respectively. OCDD, PCB-138 and PBDE-47 were the dominant compounds according to their respective congeners. WHO 98-TEQ (PCDD/PCDF/PCB) for fatty fish and shell fish were 0.60 and 0.070 pg g(-1) wet weight, respectively, lower than the standard set by the European Commission. The contamination levels and profiles were compared with those documented in previous publications.

  5. Introduced and native congeners use different resource allocation strategies to maintain performance during infection.

    PubMed

    Coon, Courtney A C; Brace, Amber J; McWilliams, Scott R; McCue, Marshall D; Martin, Lynn B

    2014-01-01

    Abstract Hosts can manage parasitic infections using an array of tactics, which are likely to vary contingent on coevolutionary history between the host and the parasite. Here we asked whether coping ability of congeners that differ in host-parasite coevolutionary history differed in response to experimental infections with a coccidian parasite. House sparrows (Passer domesticus) and gray-headed sparrows (Passer griseus) are sympatric and ecologically similar, but house sparrows are recent colonizers of Kenya, the site of our comparison, whereas gray-headed sparrows are native. We evaluated three variables as barometers of infection coping ability: vertical flight, pectoral muscle size, and fat score. We also measured routing of a dose of (13)C-labeled leucine, an essential amino acid, among tissues to compare resource allocation strategies in response to infection. We found that burden effects on performance were minimal in both species, but house sparrows maintained considerably higher burdens than gray-headed sparrows regardless of exposure. House sparrows also had more exogeneous leucine tracer in all tissues after 24 h, demonstrating a difference in the way the two species allocate or distribute resources. We argue that house sparrows may be maintaining larger resource reserves to mitigate costs associated with exposure and infection. Additionally, in response to increased parasite exposure, gray-headed sparrows had less leucine tracer in their spleens and more in their gonads, whereas house sparrows did not change allocation, perhaps indicating a trade-off that is not experienced by the introduced species. PMID:24940920

  6. 17β-Estradiol Attenuates Conduit Pulmonary Artery Mechanical Property Changes With Pulmonary Arterial Hypertension.

    PubMed

    Liu, Aiping; Tian, Lian; Golob, Mark; Eickhoff, Jens C; Boston, Madison; Chesler, Naomi C

    2015-11-01

    Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Because proximal pulmonary arterial (PA) stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to right ventricular function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia. Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of smooth muscle cell activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P<0.05). 17β-Estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via right ventricular catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH. PMID:26418020

  7. 17β-estradiol attenuates conduit pulmonary artery mechanical property changes with pulmonary arterial hypertension

    PubMed Central

    Liu, Aiping; Tian, Lian; Golob, Mark; Eickhoff, Jens C.; Boston, Madison; Chesler, Naomi C.

    2015-01-01

    Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Since proximal PA stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to RV function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia (SuHx). Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of SMC activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P < 0.05). 17β-estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via RV catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH. PMID:26418020

  8. Methods for long-term 17β-estradiol administration to mice.

    PubMed

    Ingberg, E; Theodorsson, A; Theodorsson, E; Strom, J O

    2012-01-01

    Rodent models constitute a cornerstone in the elucidation of the effects and biological mechanisms of 17β-estradiol. However, a thorough assessment of the methods for long-term administration of 17β-estradiol to mice is lacking. The fact that 17β-estradiol has been demonstrated to exert different effects depending on dose emphasizes the need for validated administration regimens. Therefore, 169 female C57BL/6 mice were ovariectomized and administered 17β-estradiol using one of the two commonly used subcutaneous methods; slow-release pellets (0.18 mg, 60-day release pellets; 0.72 mg, 90-day release pellets) and silastic capsules (with/without convalescence period, silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with a 14 mm column of 36 μg 17β-estradiol/mL sesame oil), or a novel peroral method (56 μg 17β-estradiol/day/kg body weight in the hazelnut cream Nutella). Forty animals were used as ovariectomized and intact controls. Serum samples were obtained weekly for five weeks and 17β-estradiol concentrations were measured using radioimmunoassay. The peroral method resulted in steady concentrations within--except on one occasion--the physiological range and the silastic capsules produced predominantly physiological concentrations, although exceeding the range by maximum a factor three during the first three weeks. The 0.18 mg pellet yielded initial concentrations an order of magnitude higher than the physiological range, which then decreased drastically, and the 0.72 mg pellet produced between 18 and 40 times higher concentrations than the physiological range during the entire experiment. The peroral method and silastic capsules described in this article constitute reliable modes of administration of 17β-estradiol, superior to the widely used commercial pellets. PMID:22137913

  9. Voluntary exercise impairs initial delayed spatial alternation performance in estradiol treated ovariectomized middle-aged rats.

    PubMed

    Neese, Steven L; Korol, Donna L; Schantz, Susan L

    2013-09-01

    Estrogens differentially modulate behavior in the adult female rodent. Voluntary exercise can also impact behavior, often reversing age associated decrements in memory processes. Our research group has published a series of papers reporting a deficit in the acquisition of an operant working memory task, delayed spatial alternation (DSA), following 17β-estradiol treatment to middle-aged ovariectomized (OVX) rats. The current study examined if voluntary exercise could attenuate the 17β-estradiol induced deficits on DSA performance. OVX 12-month old Long-Evans rats were implanted with a Silastic capsule containing 17β-estradiol (10% in cholesterol: low physiological range) or with a blank capsule. A subset of the 17β-estradiol and OVX untreated rats were given free access to a running wheel in their home cage. All rats were tested for 40 sessions on the DSA task. Surprisingly, we found running wheel access to impair initial acquisition of the DSA task in 17β-estradiol treated rats, an effect not seen in OVX untreated rats given running wheel access. This deficit was driven by an increase in perseverative responding on a lever no longer associated with reinforcement. We also report for the first time a 17β-estradiol induced impairment on the DSA task following a long intertrial delay (18-sec), an effect revealed following more extended testing than in our previous studies (15 additional sessions). Overall, running wheel access increased initial error rate on the DSA task in 17β-estradiol treated middle-aged OVX rats, and failed to prevent the 17β-estradiol induced deficits in performance of the operant DSA task in later testing sessions.

  10. Polychlorinated biphenyl congener patterns in tree swallows (Tachycineta bicolor) nesting in the Housatonic River watershed, western Massachusetts, USA, using a novel statistical approach

    USGS Publications Warehouse

    Custer, Christine M.; Read, L.B.

    2006-01-01

    A novel application of a commonly used statistical approach was used to examine differences in polychlorinated biphenyl (PCB) congener Patterns among locations and sample matrices in tree swallows (Tachycineta bicolor) nesting in the Housatonic River watershed in western Massachusetts. USA. The most prevalent PCB congeners in tree swallow tissue samples from the Housatonic River watershed were Ballsmitter Zell numbers 153. 138 180, 187 149, 101, and 170. These congeners were seven of the eight most prevalent congeners in Aroclor (R) 1260, the PCB mixture that was the primary source of contamination in the Housatonic River system. Using paired-Euclidean distances and tolerance limits, it was demonstrated that conuener patterns in swallow tissues from sites on the main stem of the Housatonic River were more similar to one another than to two sites upstream of the contamination or from a nearby reference area. The congener patterns also differed between the reference area and the two upstream tributaries and between the two tributaries. These pattern differences were the same in both pipper (eggs or just hatched nestlings) and 12-day-old nestling samples. Lower-chlorinated congeners appeared to be metabolized in nestlings and pippers compared to diet. and metabolized more in pippers compared to nestlings. Euclidean distances and tolerance limits provide a simple and statistically valid method to compare PCB congener patterns among groups. Published by Elsevier Ltd.

  11. SEX, ESTRADIOL, AND SPATIAL MEMORY IN A FOOD-CACHING CORVID

    PubMed Central

    Rensel, Michelle A.; Ellis, Jesse M.S.; Harvey, Brigit; Schlinger, Barney A.

    2015-01-01

    Estrogens significantly impact spatial memory function in mammalian species. Songbirds express the estrogen synthetic enzyme aromatase at relatively high levels in the hippocampus and there is evidence from zebra finches that estrogens facilitate performance on spatial learning and/or memory tasks. It is unknown, however, whether estrogens influence hippocampal function in songbirds that naturally exhibit memory-intensive behaviors, such as cache recovery observed in many corvid species. To address this question, we examined the impact of estradiol on spatial memory in non-breeding Western scrub-jays, a species that routinely participates in food caching and retrieval in nature and in captivity. We also asked if there were sex differences in performance or responses to estradiol. Utilizing a combination of an aromatase inhibitor, fadrozole, with estradiol implants, we found that while overall cache recovery rates were unaffected by estradiol, several other indices of spatial memory, including searching efficiency and efficiency to retrieve the first item, were impaired in the presence of estradiol. In addition, males and females differed in some performance measures, although these differences appeared to be a consequence of the nature of the task as neither sex consistently out-performed the other. Overall, our data suggest that a sustained estradiol elevation in a food-caching bird impairs some, but not all, aspects of spatial memory on an innate behavioral task, at times in a sex-specific manner. PMID:26232613

  12. Consequences of nongenomic actions of estradiol on pathogenic genital tract response

    PubMed Central

    2013-01-01

    Estradiol is a steroid hormone that regulates the structure and function of the female reproductive system. In addition to its genomic effects, which are mediated by activated nuclear receptors, estradiol elicits a variety of rapid signaling events independently of transcriptional or genomic regulation. These nongenomic actions influence the milieu of the genital tract, which changes the ability of pathogens to infect the genital tract. This review discusses our current knowledge regarding the mechanisms and relevance of nongenomic estradiol signaling in the genital tract that could change the ability of pathogens to invade epithelial cells. PubMed was searched through January 1980 for papers related to estradiol actions in the ovary, fallopian tube, uterus and cervix. The mechanisms conveying these rapid effects consist of a multitude of signaling molecules and include cross-talk with slower transcriptional actions. The nongenomic actions of estradiol that influence the infectious abilities of pathogens occur either directly on the genital tract cells or indirectly by modulating the local and systemic immune systems. Additional in-depth characterization of the response is required before the normal and pathological reproductive functions of the nongenomic estradiol pathway can be targeted for pharmacological intervention. PMID:23351368

  13. Women with an avoidant attachment style show attenuated estradiol responses to emotionally intimate stimuli.

    PubMed

    Edelstein, Robin S; Kean, Emily L; Chopik, William J

    2012-02-01

    The current study examined neuroendocrine processes associated with emotional intimacy in humans. Despite the importance of this aspect of close relationships, emotional intimacy has received much less attention in neuroendocrine research compared to other aspects of close relationships. In this study, participants viewed movie clips depicting an emotionally intimate parent-child interaction or other, non-intimate themes, and we assessed whether depictions of emotional intimacy increased levels of estradiol, a steroid hormone associated with attachment and caregiving processes. We also examined whether estradiol responses were moderated by individual differences in attachment avoidance, or people's discomfort with closeness and intimacy. Our findings revealed that, among single participants, estradiol levels increased in response to the emotionally intimate clip, but this effect was not observed among currently partnered participants. Moreover, the effects of emotional intimacy were moderated by gender and attachment avoidance, such that highly avoidant women showed smaller increases in estradiol after watching the emotionally intimate clip. Women's avoidance was unrelated to estradiol responses in the non-intimate control conditions, however, suggesting that the effects of avoidance were specific to intimate contexts. Taken together, the current findings contribute to our understanding of the biological bases of attachment and caregiving processes. They also highlight the potential role of estradiol in avoidant individuals' regulation of closeness and intimacy.

  14. Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

    PubMed Central

    Scholz, Paul; Mohrhardt, Julia; Gisselmann, Günter; Hatt, Hanns

    2016-01-01

    The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30. PMID:27494699

  15. Involvement of atrial natriuretic peptide in blood pressure reduction induced by estradiol in spontaneously hypertensive rats.

    PubMed

    Belo, Najara O; Silva-Barra, Juliana; Carnio, Evelin C; Antunes-Rodrigues, Jose; Gutkowska, Jolanta; Dos Reis, Adelina M

    2004-01-15

    The aim of the present study was to determine the involvement of atrial natriuretic peptide (ANP) in blood pressure (BP) alterations induced by estradiol treatment. Spontaneously hypertensive rats (SHR) and Wistar rats (WR) were ovariectomized and, after 3 weeks, were injected daily for 4 days with estradiol benzoate (E2; 5 microg/100 g/day) or a vehicle. One day after the last injection, the animals were decapitated, blood was collected, and both right and left atrial appendages were quickly removed for determination of ANP by radioimmunoassay (RIA), or used for ANP mRNA determination. Estradiol treatment induced a significant reduction of blood pressure in SHR, but not in WR. This reduction was correlated with the increase of plasma ANP levels that were significantly increased in E2-treated, compared with vehicle-treated, SHR. E2-treated SHR showed significant increases in ANP concentration in the right and left atria compared to the vehicle-treated animals. These observations were confirmed by ANP mRNA. In summary, the present study shows that short-term estradiol treatment reduces the blood pressure of ovariectomized SHR, but not of WR. This reduction was highly correlated with increased plasma estradiol and ANP levels. These results suggest that ANP is involved in mediating the effect of estradiol on blood pressure reduction.

  16. Sex, estradiol, and spatial memory in a food-caching corvid.

    PubMed

    Rensel, Michelle A; Ellis, Jesse M S; Harvey, Brigit; Schlinger, Barney A

    2015-09-01

    Estrogens significantly impact spatial memory function in mammalian species. Songbirds express the estrogen synthetic enzyme aromatase at relatively high levels in the hippocampus and there is evidence from zebra finches that estrogens facilitate performance on spatial learning and/or memory tasks. It is unknown, however, whether estrogens influence hippocampal function in songbirds that naturally exhibit memory-intensive behaviors, such as cache recovery observed in many corvid species. To address this question, we examined the impact of estradiol on spatial memory in non-breeding Western scrub-jays, a species that routinely participates in food caching and retrieval in nature and in captivity. We also asked if there were sex differences in performance or responses to estradiol. Utilizing a combination of an aromatase inhibitor, fadrozole, with estradiol implants, we found that while overall cache recovery rates were unaffected by estradiol, several other indices of spatial memory, including searching efficiency and efficiency to retrieve the first item, were impaired in the presence of estradiol. In addition, males and females differed in some performance measures, although these differences appeared to be a consequence of the nature of the task as neither sex consistently out-performed the other. Overall, our data suggest that a sustained estradiol elevation in a food-caching bird impairs some, but not all, aspects of spatial memory on an innate behavioral task, at times in a sex-specific manner. PMID:26232613

  17. Analyses of synovial tissues from arthritic and protected congenic rat strains reveal a new core set of genes associated with disease severity

    PubMed Central

    Brenner, Max; Laragione, Teresina

    2013-01-01

    Little is known about the genes regulating disease severity and joint damage in rheumatoid arthritis (RA). In the present study we analyzed the gene expression characteristics of synovial tissues from four different strains congenic for non-MHC loci that develop mild and nonerosive arthritis compared with severe and erosive DA rats. DA.F344(Cia3d), DA.F344(Cia5a), DA.ACI(Cia10), and DA.ACI(Cia25) rats developed mild arthritis compared with DA. We found 685 genes with significantly different expression between congenics and DA, independent of the specific congenic interval, suggesting that these genes represent a new nongenetic core group of mediators of arthritis severity. This core group includes genes not previously implicated or with unclear role in arthritis severity, such as Tnn, Clec4m, and Spond1 among others, increased in DA. The core genes also included Scd1, Selenbp1, and Slc7a10, increased in congenics. Genes implicated in nuclear receptor activity, xenobiotic and lipid metabolism were also increased in the congenics, correlating with protection. Several disease mediators were among the core genes reduced in congenics, including IL-6, IL-17, and Ccl2. Analyses of upstream regulators (genes, pathways, or chemicals) suggested reduced activation of Stat3 and TLR-related genes and chemicals in congenics. Additionally, cigarette smoking was among the upstream regulators activated in DA, while p53 was an upstream regulator activated in congenics. We observed congenic-specific differential expression and detection in each individual strain. In conclusion, this new nongenetically regulated core genes of disease severity or protection in arthritis should provide new insight into critical pathways and potential new environmental risk factor for arthritis. PMID:24046282

  18. Fate of 17β-estradiol in anaerobic lagoon digesters.

    PubMed

    Hakk, Heldur; Sikora, Lawrence; Casey, Francis X M; Larsen, Gerald L

    2014-03-01

    The fate of [C]17β-estradiol ([C]E2) was monitored for 42 d in triplicate 10-L anaerobic digesters. Total radioactive residues decreased rapidly in the liquid layer of the digesters and reached a steady-state value of 22 to 26% of the initial dose after 5 d. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analyses of the liquid layer of the anaerobic digesters indicated a rapid degradation of E2 to estrone (E1), which readily adsorbed to the sludge layer subsequent to its formation. Estrone was the predominant steroid identified under anaerobic digestion in the liquid layer or sorbed to sludge at 42 d. Methane formation represented 11.1 ± 5.7% of the initial E2 fortification with 0.3 to 0.5% of the starting E2 mineralized to carbon dioxide. Maximum [C]methane production appeared between Days 4 and 7. An estimate of estrogenicity of the final product based on reported estrogen equivalents for E1 and E2 was 2% of the original in active digesters. Anaerobic digestion of swine waste has several management benefits; moreover, this study demonstrated that it reduces the potential of environmental release of estrogens, which are known endocrine disruptors. PMID:25602671

  19. The concentration of estradiol-17 beta in bovine semen.

    PubMed

    Godfrey, R W; Randel, R D; Forrest, D W; Senger, P L

    1985-03-01

    This study was conducted to evaluate the influence of age, breed, epididymectomy and semen processing on the concentration of estradiol-17 beta (E2) in bovine semen. Semen was collected either by electroejaculation or with an artificial vagina. Neat semen samples were stored at -20 C until analysis. Processed, frozen semen and an egg yolk-citrate semen extender were obtained from a commercial semen processing firm and stored in liquid nitrogen at -196 C. The concentration of E2 in semen was determined by radioimmunoassay. Semen from mature (greater than 24 mo), fertile Brahman (n = 19), Brangus (n = 16), Charolais (n = 29), Holstein (n = 15) and Santa Gertrudis (n = 25) bulls was analyzed for E2 concentration, and no difference (P greater than .10) between breeds was found. There was no difference (P greater than .10) in seminal E2 concentration between mature, fertile bulls (n = 104) and epididymectomized bulls (n = 22). In semen collected from prepuberal (12 to 16 mo, n = 21), peripuberal (17 to 20 mo, n = 17) and mature (greater than 24 mo, n = 19), Brahman bulls, the mature bulls had a lower (P less than .01) semen E2 concentration than peripuberal and prepuberal bulls. There were no differences (P greater than .10) in seminal E2 concentration among peripuberal Angus (n = 8), Hereford (n = 8) and Brahman (n = 17) bulls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3988647

  20. Estradiol protective role in atherogenesis through LDL structure modification

    NASA Astrophysics Data System (ADS)

    Papi, Massimiliano; Brunelli, Roberto; Ciasca, Gabriele; Maiorana, Alessandro; Maulucci, Giuseppe; Palmieri, Valentina; Parasassi, Tiziana; De Spirito, Marco

    2016-07-01

    Relevant physiological functions are exerted by circulating low density lipoprotein (LDL) as well as eventual pathological processes triggering atherogenesis. Modulation of these functions can well be founded on modifications of LDL structure. Given its large dimension, multicomponent organization and strong interactions between the protein apoB-100 and lipids, determining LDL 3D structure remains a challenge. We propose a novel quantitative physical approach to this complex biological problem. We introduce a three-component model, fitted to small angle x-ray scattering data on LDL maintained in physiological conditions, able to achieve a consistent 3D structure. Unexpected features include three distinct protein domains protruding out of a sphere, quite rough in its surface, where several core lipid areas are exposed. All LDL components are affected by 17-β-estradiol (E2) binding to apoB-100. Mostly one of the three protruding protein domains, dramatically reducing its presence on the surface and with a consequent increase of core lipids’ exposure. This result suggests a structural basis for some E2 protecting roles and LDL physiological modifications.

  1. Estradiol replacement extends the window of opportunity for hippocampal function.

    PubMed

    Vedder, Lindsey C; Bredemann, Teruko M; McMahon, Lori L

    2014-10-01

    We previously reported that treating aged female rats, ovariectomized (OVX) as young adults, with acute proestrous levels of 17β estradiol (E2) increases CA1 spine density, NMDAR to AMPAR ratio, GluN2B-mediated NMDAR current, and long-term potentiation at CA3-CA1 synapses if administered by 15, but not at 19-month post-OVX, defining the critical window of opportunity. Importantly, when rats are aged with ovaries intact until OVX at 20 months, hippocampal E2 responsiveness is maintained, indicating the deficit at 19-month post-OVX is a consequence of the duration of hormone deprivation and not chronological age. Here, we find the beneficial effect of E2 on novel object recognition in OVX rats was constrained by the same critical window. Furthermore, chronic low-level E2 replacement, commenced by 11-month post-OVX using subcutaneous capsules removed 2 weeks before acute proestrous E2 treatment, prevents the loss of hippocampal responsiveness at 19-month post-OVX. These data define the dynamic nature of the critical window showing that chronic replacement with physiological E2 levels within a certain period post-OVX can lengthen the window.

  2. Estradiol regulates MICA expression in human endometrial cells

    PubMed Central

    Basu, Satarupa; Pioli, Patricia A.; Conejo-Garcia, Jose; Wira, Charles R.; Sentman, Charles L.

    2008-01-01

    The human endometrium undergoes cyclical changes regulated by sex hormones. Evidence suggests sex hormones regulate NK cell recruitment into the uterus in large numbers. NKG2D is an activating receptor expressed on human NK cells, γδ and CD8 T cells. NKG2D ligands are known to be sensors of cellular “stress”. In this study, we investigated whether sex hormones directly regulate expression of NKG2D ligands in the human uterus. Estradiol increased MICA expression on uterine epithelial cells; regulation was estrogen receptor-dependent. Real-time PCR analysis showed that NKG2D ligands MICA and MICB were expressed in the human endometrium. MICA protein was detected primarily on epithelial cells, and greater expression was observed in immunohistochemical analysis of tissues from patients in the secretory phase of the menstrual cycle. Thus, estrogens regulate expression of MICA. These data suggest hormonal regulation of innate immunity and NKG2D-mediated recognition in other tissues and diseases where estrogen may be involved. PMID:18728002

  3. Estradiol promotes the rewarding effects of nicotine in female rats.

    PubMed

    Flores, Rodolfo J; Pipkin, Joseph A; Uribe, Kevin P; Perez, Adriana; O'Dell, Laura E

    2016-07-01

    It is presently unclear whether ovarian hormones, such as estradiol (E2), promote the rewarding effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day injection regimen involving 2 days of vehicle and 2 days of E2 administration. Two doses of E2 (25 or 250μg) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on the rewarding effects of nicotine. The rats were given 23-hour access to nicotine IVSA using an escalating dose regimen (0.015, 0.03, and 0.06mg/kg/0.1mL). Each dose was self-administered for 4 days with 3 intervening days of nicotine abstinence. The results revealed that intact females displayed higher levels of nicotine intake as compared to males. Also, intact females displayed higher levels of nicotine intake versus OVX females. Lastly, our results revealed that OVX rats that received E2 supplementation displayed a dose-dependent increase in nicotine intake as compared to OVX rats that received vehicle. Together, our results suggest that the rewarding effects of nicotine are enhanced in female rats via the presence of the ovarian hormone, E2.

  4. Levels and congener profiles of polybrominated diphenyl ethers (PBDEs) in Zebra mussels (D. polymorpha) from Lake Maggiore (Italy).

    PubMed

    Binelli, A; Guzzella, L; Roscioli, C

    2008-06-01

    Several congeners of polybrominated diphenyl ethers (PBDEs) were monitored in 14 different sampling stations of Lake Maggiore, the second largest Italian lake in regard to surface, volume and average depth, using the sentinel-organism Zebra mussel (Dreissena polymorpha). Results revealed a moderate contamination with summation operatorPBDE levels (BDE-17, -28, -47, -66, -71, -85, -99, -100, -138, -153, -154, -183, -190 and -209) ranging from 40 to 447ngg(-1) lipid weight which are similar to those found in environments polluted by deposition or atmospheric transport. The general order of decreasing congener contribution to the total load was BDE-47>-99>-100>-209, which closely reflected patterns observed in mussels collected in freshwater ecosystems worldwide.

  5. Temporal and spatial trends in total PCB and PCB congeners in biota in a river-reservoir system

    SciTech Connect

    Horwitz, R.J.; McNair, J.N.; Hermanson, M.H.

    1995-12-31

    Since 1984, biennial studies of PCBs have been conducted in fishes, crayfish and insects in the Housatonic River, CT., and additional data are available from earlier studies. PCB data quantitated from presumptive Aroclor concentrations overestimated total PCB concentrations ([TPCB]) by about 13%, although the estimates by the 2 methods were very highly correlated. Ages of all fish specimens were determined. Spatial and temporal trends in [TPCB] were analyzed using ANCOVA to adjust for relationships between [TPCB] and age, lipid content, location and sex. Adjusted [TPCB] consistently decreased in the downstream direction. [TPCB] decreased within the years after cessation of direct inputs (around 1978). However, in the 1984--1992 period [TPCB] trends were weak and variable. Concentrations in 1994 were lower than previous years (statistical comparisons showing 1994 to be the lowest year or among a group of years with the lowest concentrations). Between year differences were probably related to temperature, storm flows and other factors affecting availability and accumulation. These variations were greater in riverine sites than in reservoirs. In brown trout, [TPCB] increased rapidly within 1--2 months after stocking. Over longer periods, [TPCB] were more closely related to seasonal cycles in lipid content rather than to time in river. Increases in [TPCB] with age were most evident for long-lived species in reservoirs. Several congeners which are abundant in Aroclors 1254 and 1260 predominated the samples. However, spatial and temporal differences in accumulation of different congeners were evident. Spatial differences in the concentration of some marker congeners reflected enrichment of these congeners from original Aroclor 1254 and 1260 sources, as well as supplemental inputs of Aroclor 1242.

  6. Laboratory Estimation of Net Trophic Transfer Efficiencies of PCB Congeners to Lake Trout (Salvelinus namaycush) from Its Prey

    PubMed Central

    Madenjian, Charles P.; Rediske, Richard R.; O'Keefe, James P.; David, Solomon R.

    2014-01-01

    A technique for laboratory estimation of net trophic transfer efficiency (γ) of polychlorinated biphenyl (PCB) congeners to piscivorous fish from their prey is described herein. During a 135-day laboratory experiment, we fed bloater (Coregonus hoyi) that had been caught in Lake Michigan to lake trout (Salvelinus namaycush) kept in eight laboratory tanks. Bloater is a natural prey for lake trout. In four of the tanks, a relatively high flow rate was used to ensure relatively high activity by the lake trout, whereas a low flow rate was used in the other four tanks, allowing for low lake trout activity. On a tank-by-tank basis, the amount of food eaten by the lake trout on each day of the experiment was recorded. Each lake trout was weighed at the start and end of the experiment. Four to nine lake trout from each of the eight tanks were sacrificed at the start of the experiment, and all 10 lake trout remaining in each of the tanks were euthanized at the end of the experiment. We determined concentrations of 75 PCB congeners in the lake trout at the start of the experiment, in the lake trout at the end of the experiment, and in bloaters fed to the lake trout during the experiment. Based on these measurements, γ was calculated for each of 75 PCB congeners in each of the eight tanks. Mean γ was calculated for each of the 75 PCB congeners for both active and inactive lake trout. Because the experiment was replicated in eight tanks, the standard error about mean γ could be estimated. Results from this type of experiment are useful in risk assessment models to predict future risk to humans and wildlife eating contaminated fish under various scenarios of environmental contamination. PMID:25226430

  7. Laboratory estimation of net trophic transfer efficiencies of PCB congeners to lake trout (Salvelinus namaycush) from its prey

    USGS Publications Warehouse

    Madenjian, Charles P.; Rediske, Richard R.; O'Keefe, James P.; David, Solomon R.

    2014-01-01

    A technique for laboratory estimation of net trophic transfer efficiency (γ) of polychlorinated biphenyl (PCB) congeners to piscivorous fish from their prey is described herein. During a 135-day laboratory experiment, we fed bloater (Coregonus hoyi) that had been caught in Lake Michigan to lake trout (Salvelinus namaycush) kept in eight laboratory tanks. Bloater is a natural prey for lake trout. In four of the tanks, a relatively high flow rate was used to ensure relatively high activity by the lake trout, whereas a low flow rate was used in the other four tanks, allowing for low lake trout activity. On a tank-by-tank basis, the amount of food eaten by the lake trout on each day of the experiment was recorded. Each lake trout was weighed at the start and end of the experiment. Four to nine lake trout from each of the eight tanks were sacrificed at the start of the experiment, and all 10 lake trout remaining in each of the tanks were euthanized at the end of the experiment. We determined concentrations of 75 PCB congeners in the lake trout at the start of the experiment, in the lake trout at the end of the experiment, and in bloaters fed to the lake trout during the experiment. Based on these measurements, γ was calculated for each of 75 PCB congeners in each of the eight tanks. Mean γ was calculated for each of the 75 PCB congeners for both active and inactive lake trout. Because the experiment was replicated in eight tanks, the standard error about mean γ could be estimated. Results from this type of experiment are useful in risk assessment models to predict future risk to humans and wildlife eating contaminated fish under various scenarios of environmental contamination.

  8. A divergent approach to the synthesis of simplexides and congeners via a late-stage olefin cross-metathesis reaction.

    PubMed

    Li, Jiakun; Li, Wei; Yu, Biao

    2013-08-14

    Simplexides constitute a unique group of immunosuppressive glycolipids that demonstrate antiproliferative activities against activated T-cell lymphocytes via a unique non-cytotoxic inhibition. To investigate the structure-activity relationship of the varied long-chain secondary alcohols on simplexides, we developed an efficient and divergent route to the synthesis of simplexides and congeners, taking advantage of a late-stage olefin cross-metathesis reaction.

  9. Determining indicator toxaphene congeners in soil using comprehensive two-dimensional gas chromatography-tandem mass spectrometry.

    PubMed

    Zhu, Shuai; Gao, Lirong; Zheng, Minghui; Liu, Huimin; Zhang, Bing; Liu, Lidan; Wang, Yiwen

    2014-01-01

    Toxaphene, which is a broad spectrum chlorinated pesticide, is a complex mixture of several hundred congeners, mainly polychlorinated bornanes. Quantifying toxaphene in environmental samples is difficult because of its complexity, and because each congener has a different response factor. Toxaphene chromatograms acquired using one-dimensional gas chromatography (1DGC) show that this technique cannot be used to separate all of the toxaphene congeners. We developed and validated a sensitive and quantitative method for determining three indicator toxaphene congeners in soil using an isotope dilution/comprehensive two-dimensional gas chromatography-tandem mass spectrometry (GC × GC-MS). The samples were extracted using accelerated solvent extraction, and then the extracts were purified using silica gel columns. (13)C₁₀-labeled Parlar 26 and 50 were used as internal standards and (13)C₁₀-labeled Parlar 62 was used as an injection standard. The sample extraction and purification treatments and the GC × GC-MS parameters were optimized. Subsequently the samples were determined by GC × GC-MS. The limits of detection for Parlar 26, 50, and 62 were 0.6 pg/g, 0.4 pg/g, and 1.0 pg/g (S/N=3), respectively, and the calibration curves had good linear correlations between 50 and 1000 μg/L (r(2)>0.99). Comprehensive two-dimensional GC gave substantial improvements over one-dimensional GC in the toxaphene analysis. We analyzed soil samples containing trace quantities of toxaphene to demonstrate that the developed method could be used to analyze toxaphene in environmental samples.

  10. Skin graft rejection in mice repopulated with marrow of the skin donor type: a Skn gene in a congenic line

    SciTech Connect

    Harrison, D.E.; Mobraaten, L.E.

    1984-01-01

    Genetically anemic W/Wv mice and lethally irradiated wild-type mice were cured and populated by grafted marrow cells from donor mice of three congenic lines that differed at non-H-2 histocompatibility loci. Tail skin from mice of the same congenic lines was grafted 3-4 weeks later. In two cases, the recipients behaved as expected, no longer rejecting skin syngeneic with the marrow graft that had repopulated them. However, B6-H-24c skin was rejected by WBB6F1-W/Wv mice that were cured with B6-H-24c marrow showing a mean survival time of 9.9 weeks. It was rejected somewhat faster, with a mean survival time of 5.9 weeks, by W/Wv mice cured with marrow from other types of donors. Results were more variable in lethally irradiated WBB6F1-+/+ recipients of B6-H-24c marrow, but they also rejected B6-H-24c skin. Both types of recipients remained chimeras after the skin was rejected, showing more than 90% of the B6-H-24c hemoglobin type. This is the first report of a Skn gene in a congenic line.

  11. Levels and distribution patterns of polychlorinated biphenyl congeners in surface sediments from Galicia coast (Northwestern, Spain) according to granulometric characteristics.

    PubMed

    Carro, N; García, I; Ignacio, M; Moureira, A

    2002-08-01

    In order to know distribution patterns of polychlorinated biphenyl congeners in the marine environment from Galida, PCBs n degrees 31, 28, 52, 101, 118, 153, 105, 138, 156 and 180 were isolated by Soxhlet extraction from three fractions of different particle size (<0.063 mm, 0.063-0.2 mm and >0.2 mm) in surface marine sediments; the quantification was performed using GC-MS and GC-ECD. Distribution of PCB congeners was shifted in favour of higher chlorinated compounds (CBs 138,153 and 180) and highly correlated to TOC content. In general, the finest fractions (<0.063 mm) of sediment presented the highest loadings of PCBs, only the sediment from As Pías zone exhibited the highest concentration of chlorinated congeners in the coarsest fraction. CB 52 concentration, slightly volatile compound, was related to water temperature. By means of multivariate techniques of data exploration as hierarchical duster analysis and principal components analysis, sediment samples from un-contaminated and slightly contaminated areas were clearly separated; groupings between samples from nearby zones appeared.

  12. Cytochrome P450 responses and PCB congeners in pipping heron embryos from Virginia, the Great Lakes and San Francisco Bay

    USGS Publications Warehouse

    Rattner, B.A.; Melancon, M.J.; Custer, T.W.; Tillett, D.E.; Woodin, Bruce R.; Stegeman, John J.

    1992-01-01

    Pipping black-crowned night-heron (Nvcticorax nvcticorax) embryos were collected from undisturbed (Chincoteague National Wildlife Refuge VA; CNWR) and industrialized (Cat Island, Green Bay WI and San Francisco Bay, CA; SFB) locations. Hepatic monooxygenases (AHH, EROD, BROD, ECOD) were induced up to 100-fold, and were correlated (r=0.50 to 0.72) with total PCB burdens (N =61 embryos). A subset of 30 embryos have now been analyzed by GC/MS for 12 AHH-active PCB congeners and by Western blot for cytochromes P450lA and P450llB. At Cat Island, concentrations of 8 congeners were greater (P <0.05) than at CNWR. P450lA and P450llB were detected in 44% and 100% of the Cat Island embryos compared to 8% and 33% of the CNWR + SFB embryos. Cytochrome P450 parameters were correlated with the total PCBs (r =0.44 to 0.67) and with at least 9 PCB congeners (r =0.39 to 0.77). Since P450 responses might be affected by other contaminants, sample extract potency in the H411E rat hepatoma bioassay is being determined to study relationships among dioxin equivalents and cytochrome P450 parameters.

  13. PCB congener analysis of water and caddisfly larvae (Insecta:Trichoptera) in the upper Hudson River by glass capillary chromatography

    SciTech Connect

    Bush, B.; Simpson, K.W.; Shane, L.; Koblintz, R.R.

    1985-01-01

    The separation and analysis of the constituents of industrially produced polychlorinated biphenyls (PCBs) has been almost exclusively performed using techniques involving packed gas chromatographic columns. However, the packed column chromatograms proved to be inadequate with regard to the separation of the many congeners which compose the complex PCB mixtures. Unlike the packed column methods, a separation technique based upon gas capillary technology produces chromatograms with sharp peaks, and hence accurate analysis is possible according to individual congener concentrations. This capability permitted more precise analysis of macroinvertebrates - specifically aquatic insects in the polluted water of the upper Hudson River. This study examines the presence and relative concentration of 74 congeners in water and caddisfly larvae collected from 3 sites in the Hudson River. Caddisfly larvae (Insecta:Trichoptera) usually dominate the macroinvertebrate communities in riffle habitats of the study area. Their relatively large size and abundance facilitated the acquisition of sufficient biomass for analysis (200 mg wet weight). The sampling was carried out on July 6, 1983 and August 15, 1983.

  14. Seasonal variability of polychlorinated biphenyls (PCBs) and polychlorinated diphenyl ethers (PBDEs) congener profiles in butter in Poland: dietary risk evaluation.

    PubMed

    Roszko, Marek; Szymczyk, Krystyna; Rzepkowska, Małgorzata; Jędrzejczak, Renata

    2014-01-01

    Various statistical methods have been employed to analyse in details seasonal diversification of polychlorinated biphenyl (PCB)/polybrominated diphenyl ether (PBDE) congener profiles found in butter fat. The variability of the PCB/PBDE congener profiles indicates the presence of various sources of the milk fat contamination. The obtained results suggest that the environmental chemical background has the highest share in the contamination sources pattern. Ion trap mass spectrometry coupled to high-resolution gas chromatography with semi-permeable membrane dialysis sample cleanup was used for determination of PCBs and PBDEs in milk fat. Determined butter fat PCB profiles were similar to the profiles characteristic for Aroclor 1254 technical mixture. Our data indicate that dietary intake of PCB/PBDE with milk and milk products may be estimated to be about 717.5 pg kg b.w.(-1) day(-1) for six-indicator PCBs, 0.329 (equivalent toxicity, TEQ) pg kg b.w.(-1) day(-1) for 12 DL PCBs and 50 pg kg b.w.(-1) day(-1) for PBDEs (sum of 14 congeners).

  15. Congener specific determination and enantiomeric ratios of chiral polychlorinated biphenyls in striped dolphins (Stenella coeruleoalba) from the Mediterranean Sea

    SciTech Connect

    Reich, S.; Schurig, V.; Jimenez, B.; Hernandez, L.M.; Gonzalez, M.J.; Marsili, L.

    1999-06-01

    Blubber and liver samples from six striped dolphins (Stenella coeruleoalba) found dead in the Mediterranean Sea in 1989--1990 were tested for 37 coplanar and chiral polychlorinated biphenyls (PCBs), including the enantiomeric ratios of 9 chiral PCBs. The method includes a fractionation step using HPLC (PYE column) for separating the PCBs according to the number of chlorine atoms in the ortho positions. HRGC/ECD and HRGC/LRMS with an a chiral column (DB-5) were used to determine the PCB congeners. The enantiomeric ratios of nine chiral PCBs were determined by HRGC/LRMS (SIM) with a chiral column (Chirasil-Dex) and by MDGC as the confirmatory technique. The total PCB concentration (sum of 37 congeners) ranged from 7.2 to 89.6 {micro}g/g (wet weight) and from 0.52 to 29.2 {micro}g/g (wet weight) for blubber and liver samples, respectively. PCB profiles were dominated by congeners 138, 153, 170, and 180. The toxic equivalent values (TEQ) ranged from 0.17 to 3.93 ng/g (wet weight) and from 0.02 to 0.73 ng/g (wet weight) for blubber and liver samples, respectively. PCBs 95, 132, 135, 149, and 176 revealed an enantiomeric excess of the second eluted enantiomer in almost all of the samples, whereas PCBs 136 and 174 were racemic or almost racemic. PCBs 88 and 91 were under the detection limits of the methodology used.

  16. Polychlorinated biphenyl source attribution in Green Bay, Wisconsin, USA, using multivariate similarity among congener profiles in sediment samples.

    PubMed

    Cacela, Dave; Beltman, Douglas J; Lipton, Joshua

    2002-08-01

    Polychlorinated biphenyl (PCB) congener concentrations measured in 1,189 sediment samples from Green Bay (MI/WI, USA), Lake Michigan (MI/WI, USA), and the Fox River (WI, USA) were analyzed statistically to evaluate whether PCB congener profiles in outer Green Bay are more similar to those observed in inner Green Bay or Lake Michigan. Similarities among PCB profiles were assessed with complementary multivariate analysis techniques: Principal component analysis (PCA), cluster analysis, and classification trees. The PCA indicated that profiles in outer Green Bay are distinct from those of inner Green Bay or Lake Michigan but are more similar to those of inner Green Bay. The outer bay profiles are dissimilar to profiles that would result from a simple process of mixing contaminated sediments from the inner bay with Lake Michigan sediments and, therefore, support the conclusion that contaminants in outer Green Bay come from discharges of the Fox River. Several classification trees based on small sets of congener proportions defined simple rules that consistently distinguished the regional profiles. Application of these rules to classify the outer bay samples suggests that the profiles of less than 7% of outer bay samples are similar to Lake Michigan profiles. These results are interpreted with respect to physical transport and chemical weathering processes that may account for the observed differences.

  17. Photochemical decomposition of 15 polybrominated diphenyl ether congeners in methanol/water.

    PubMed

    Eriksson, Johan; Green, Nicholas; Marsh, Göran; Bergman, Ake

    2004-06-01

    Among all brominated flame retardants in use, the polybrominated diphenyl ethers (PBDEs) have been identified as being of particular environmental concern due to their global distribution and bioaccumulating properties, as observed in humans and wildlife worldwide. Still there is a need for more data on the basic characteristics of PBDEs to better understand and describe their environmental fate. Hence, the aim of this study was to investigate the photochemical degradation of PBDEs with different degrees of bromination. The photochemical degradation of 15 individual PBDEs substituted with 4-10 bromine atoms was studied in methanol/water (8:2) by UV light in the sunlight region. Nine of these were also studied in pure methanol, and four of the nine PBDEs were studied in tetrahydrofuran. The photochemical reaction rate decreased with decreasing number of bromine substituents in the molecule but also in some cases influenced by the PBDE substitution pattern. The reaction rate was dependent on the solvent in such a way that the reaction rate in a methanol/water solution was consistently around 1.7 times lower than in pure methanol and 2-3 times lower than in THF. The UV degradation half-life of decaBDE (T1/2 = 0.5 h) was more than 500 times shorter than the environmentally abundant congener 2,2',4,4'-tetraBDE (T1/2 = 12 d) in methanol/water. The quantum yields in the methanol/water solution ranged from 0.1 to 0.3. The photochemical reaction of decaBDE is a consecutive debromination from ten- down to six-bromine-substituted PBDEs. Products with less than six bromines were tentatively identified as brominated dibenzofurans and traces of what was indicated as methoxylated brominated dibenzofurans. PMID:15224744

  18. Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans

    PubMed Central

    Khan, Amber; Manzoor, Nikhat; Molepo, Julitha

    2015-01-01

    We previously reported the antifungal properties of a monoterpene phenol “Eugenol” against different Candida strains and have observed that the addition of methyl group to eugenol drastically increased its antimicrobial potency. Based on the results and the importance of medicinal synthetic chemistry, we synthesized eugenol-tosylate and its congeners (E1-E6) and tested their antifungal activity against different clinical fluconazole (FLC)- susceptible and FLC- resistant C. albicans isolates alone and in combination with FLC by determining fractional inhibitory concentration indices (FICIs) and isobolograms calculated from microdilution assays. Minimum inhibitory concentration (MIC) results confirmed that all the tested C. albicans strains were variably susceptible to the semi-synthetic derivatives E1-E6, with MIC values ranging from 1–62 μg/ml. The test compounds in combination with FLC exhibited either synergy (36%), additive (41%) or indifferent (23%) interactions, however, no antagonistic interactions were observed. The MICs of FLC decreased 2–9 fold when used in combination with the test compounds. Like their precursor eugenol, all the derivatives showed significant impairment of ergosterol biosynthesis in all C. albicans strains coupled with down regulation of the important ergosterol biosynthesis pathway gene-ERG11. The results were further validated by docking studies, which revealed that the inhibitors snugly fitting the active site of the target enzyme, mimicking fluconazole, may well explain their excellent inhibitory activity. Our results suggest that these compounds have a great potential as antifungals, which can be used as chemosensitizing agents with the known antifungal drugs. PMID:26694966

  19. Supervised pattern recognition procedures for discrimination of whiskeys from gas chromatography/mass spectrometry congener analysis.

    PubMed

    González-Arjona, Domingo; López-Pérez, Germán; González-Gallero, Víctor; González, A Gustavo

    2006-03-22

    The volatile congener analysis of 52 commercialized whiskeys (24 samples of single malt Scotch whiskey, 18 samples of bourbon whiskey, and 10 samples of Irish whiskey) was carried out by gas chromatography/mass spectrometry after liquid-liquid extraction with dichloromethane. Pattern recognition procedures were applied for discrimination of different whiskey categories. Multivariate data analysis includes linear discriminant analysis (LDA), k nearest neighbors (KNN), soft independent modeling of class analogy (SIMCA), procrustes discriminant analysis (PDA), and artificial neural networks techniques involving multilayer perceptrons (MLP) and probabilistic neural networks (PNN). Classification rules were validated by considering the number of false positives (FPs) and false negatives (FNs) of each class associated to the prediction set. Artificial neural networks led to the best results because of their intrinsic nonlinear features. Both techniques, MLP and PNN, gave zero FPs and zero FNs for all of the categories. KNN is a nonparametric method that also provides zero FPs and FNs for every class but only when selecting K = 3 neighbors. PDA produced good results also (zero FPs and FNs always) but only by selecting nine principal components for class modeling. LDA shows a lesser classification performance, because of the building of linear frontiers between classes that does not apply in many real situations. LDA led to one FP for bourbons and one FN for scotches. The worse results were obtained with SIMCA, which gave a higher number of FPs (five for both scotches and bourbons) and FNs (six for scotchs and two for bourbons). The possible cause of these findings is the strong influence of class inhomogeneities on the SIMCA performance. It is remarkable that in any case, all of the methodologies lead to zero FPs and FNs for the Irish whiskeys.

  20. Comparative developmental toxicity of planar polychlorinated biphenyl congeners in chickens, American kestrels, and common terns

    USGS Publications Warehouse

    Hoffman, D.J.; Melancon, M.J.; Klein, P.N.; Eisemann, J.D.; Spann, J.W.

    1998-01-01

    The effects of PCB congeners, PCB 126 (3,3',4,4',5-pentaCB) and PCB 77 (3,3'4,4'-tetraCB), were examined in chicken (Gallus gallus), American kestrel (Falco sparverius), and common tern (Sterna hirundo) embryos through hatching, following air cell injections on day 4. PCB 126 caused malformations and edema in chickens starting at 0.3 ppb, in kestrels at 2.3 ppb, but in terns only at levels affecting hatching success (44 ppb). Extent of edema was most severe in chickens and least in terns. Defects of the beak were common in all species, but with crossed beak most prevalent in terns. Effects on embryo growth were most apparent for PCB 126 in chickens and kestrels. The approximate LD50 for PCB 126 in chickens was 0.4 ppb, in kestrels was 65 ppb, and in terns was 104 ppb. The approximate LD50 for PCB 77 in chickens was 2.6 ppb and in kestrels was 316 ppb. Induction of cytochrome P450 associated monooxygenase activity (EROD activity) by PCB 126 in chick embryo liver was about 800 times more responsive than in tern and at least 1000 times more responsive than in kestrel. High concentrations of PCB 126 found in bald eagle eggs are nearly 20-fold higher than the lowest toxic concentration tested in kestrels. Concentrations of PCB 126 causing low level toxic effects in common tern eggs are comparable to highest levels in common terns and Forster's terns in the field, suggesting additional involvement of other compounds in the Great Lakes.

  1. Comparative developmental toxicity of planar polychlorinated biphenyl congeners in chickens, American kestrels, and common terns

    SciTech Connect

    Hoffman, D.J.; Melancon, M.J.; Klein, P.N.; Eisemann, J.D.; Spann, J.W.

    1998-04-01

    The effects of polychlorinated biphenyl (PCB) congeners, PCB 126 (3,3{prime},4,4{prime},5-pentaCB) and PCB 77 (3,3{prime},4,4{prime}-tetraCB), were examined in chicken (Gallus gallus), American kestrel (Falco sparverius), and common tern (Sterna hirundo) embryos through hatching, following air cell injections on day 4. PCB 126 caused malformations and edema in chickens starting at 0.3 ppb, in kestrels at 2.3 to 23 ppb, but in terns only at levels affecting hatching success (44 ppb). Extent of edema was most severe in chickens and least in terns. Defects of the beak were common in all species but with crossed beak most prevalent in terns. Effects on embryo growth were most apparent for PCB 126 in chickens and kestrels. The approximate 50% lethal dose (LD50) for PCB 126 in chickens was 0.4 ppb, in kestrels was 65 ppb, and in terns was 104 ppb. The approximate LD50 for PCB 77 in chickens was 2.6 ppb and in kestrels was 316 ppb. Induction of cytochrome P450 associated monooxygenase activity (ethoxyresorufin-O-dealkylase activity) by PCB 126 in chick embryo liver was about 800 times more responsive than in tern and at least 1,000 times more responsive than in kestrel. High concentrations of PCB 126 found in bald eagle eggs are nearly 20-fold higher than the lowest toxic concentration tested in kestrels. Concentrations of PCB 126 causing low-level toxic effects in common tern eggs are comparable to highest levels in common terns and Forster`s terns in the field, suggesting additional involvement of other compounds in the Great Lakes.

  2. Supervised pattern recognition procedures for discrimination of whiskeys from gas chromatography/mass spectrometry congener analysis.

    PubMed

    González-Arjona, Domingo; López-Pérez, Germán; González-Gallero, Víctor; González, A Gustavo

    2006-03-22

    The volatile congener analysis of 52 commercialized whiskeys (24 samples of single malt Scotch whiskey, 18 samples of bourbon whiskey, and 10 samples of Irish whiskey) was carried out by gas chromatography/mass spectrometry after liquid-liquid extraction with dichloromethane. Pattern recognition procedures were applied for discrimination of different whiskey categories. Multivariate data analysis includes linear discriminant analysis (LDA), k nearest neighbors (KNN), soft independent modeling of class analogy (SIMCA), procrustes discriminant analysis (PDA), and artificial neural networks techniques involving multilayer perceptrons (MLP) and probabilistic neural networks (PNN). Classification rules were validated by considering the number of false positives (FPs) and false negatives (FNs) of each class associated to the prediction set. Artificial neural networks led to the best results because of their intrinsic nonlinear features. Both techniques, MLP and PNN, gave zero FPs and zero FNs for all of the categories. KNN is a nonparametric method that also provides zero FPs and FNs for every class but only when selecting K = 3 neighbors. PDA produced good results also (zero FPs and FNs always) but only by selecting nine principal components for class modeling. LDA shows a lesser classification performance, because of the building of linear frontiers between classes that does not apply in many real situations. LDA led to one FP for bourbons and one FN for scotches. The worse results were obtained with SIMCA, which gave a higher number of FPs (five for both scotches and bourbons) and FNs (six for scotchs and two for bourbons). The possible cause of these findings is the strong influence of class inhomogeneities on the SIMCA performance. It is remarkable that in any case, all of the methodologies lead to zero FPs and FNs for the Irish whiskeys. PMID:16536565

  3. Time trends of polybrominated diphenylether (PBDE) congeners in serum of Swedish mothers and comparisons to breast milk data.

    PubMed

    Darnerud, Per Ola; Lignell, Sanna; Aune, Marie; Isaksson, Martin; Cantillana, Tatiana; Redeby, Johan; Glynn, Anders

    2015-04-01

    In the present study our main focus was blood serum levels and time trends of the fully brominated diphenyl ether (PBDE) BDE-209 in Swedish first-time mothers, as relatively a few human data on this congener are currently available. Also, levels and temporal trends in serum of other more commonly reported PBDE congeners and HBCD were studied. In an ongoing study on POPs in Uppsala Primiparas (POPUP), serum samples (N=413) from first-time mothers from 1996 to 2010 were used. Pooling of individual samples (5-25 individuals/pool, approx. 3 pools/year) resulted in 36 pooled samples used for PBDE/HBCD analysis on GC-LRMS. In addition, serum/breast milk correlations for PBDE and HBCD levels in 30 paired samples from individual mothers sampled 2010 were studied. The mean serum level of BDE-209 (1.3ng/g lipid wt.) was highest of all studied PBDE congeners, followed by BDE-47 and BDE-153. There was no significant temporal trend for BDE-209 during the study period, whereas the levels of BDE-47, BDE-99, BDE-100 and of HBCD decreased significantly in pooled serum 1996-2010. After omission of one outlier, a significant increasing trend was observed for BDE-153. The serum/milk PBDE quotients in paired individual samples from 2010 ranged from 0.83 to 17, with the highest quotient for BDE-209. Differences in PBDE transfer from blood to milk are probably related to molecular weight or size. The correlations between serum and milk levels of tetra- to hexa-brominated congeners were generally strong (r=0.83-0.97), but weaker for BDE-183 (r=0.57) and BDE-209 (r=0.38). Regarding HBCD, serum levels in 2010 were mostly beneath LOQ which made serum/milk quotients impossible. The decreasing levels of some BFR compounds in serum over time show that exposures have decreased after the production and use of some of these substances have been restricted. The lack of temporal trend of BDE-209 suggests that the human exposure to this congener in Sweden has been stable for more than a decade. PMID

  4. Estradiol regulation of nucleotidases in female reproductive tract epithelial cells and fibroblasts.

    PubMed

    Shen, Zheng; Fahey, John V; Bodwell, Jack E; Rodriguez-Garcia, Marta; Rossoll, Richard M; Crist, Sarah G; Patel, Mickey V; Wira, Charles R

    2013-01-01

    The use of topical and oral adenosine derivatives in HIV prevention that need to be maintained in tissues and cells at effective levels to prevent transmission prompted us to ask whether estradiol could influence the regulation of catabolic nucleotidase enzymes in epithelial cells and fibroblasts from the upper and lower female reproductive tract (FRT) as these might affect cellular TFV-DP levels. Epithelial cells and fibroblasts were isolated from endometrium (EM), endocervix (CX) and ectocervix (ECX) tissues from hysterectomy patients, grown to confluence and treated with or without estradiol prior to RNA isolation. The expression of nucleotidase (NT) genes was measurable by RT-PCR in epithelial cells and fibroblasts from all FRT tissues. To determine if sex hormones have the potential to regulate NT, we evaluated NT gene expression and NT biological activity in FRT cells following hormone treatment. Estradiol increased expression of Cytosolic 5'-nucleotidase after 2 or 4 h in endometrial epithelial cells but not epithelial cells or fibroblasts from other sites. In studies using a modified 5'-Nucleotidase biological assay for nucleotidases, estradiol increased NT activity in epithelial cells and fibroblasts from the EM, CX and ECX at 24 and 48 h. In related studies, HUVEC primary cells and a HUVEC cell line were unresponsive to estradiol in terms of nucleotidase expression or biological activity. Our findings of an increase in nucleotidase expression and biological activity induced by estradiol do not directly assess changes in microbicide metabolism. However, they do suggest that when estradiol levels are elevated during the menstrual cycle, FRT epithelial cells and fibroblasts from the EM, CX and ECX have the potential to influence microbicide levels that could enhance protection of HIV-target cells (CD4+T cells, macrophages and dendritic cells) throughout the FRT. PMID:23936114

  5. VITAMIN D–BINDING PROTEIN IN HEALTHY PRE- AND POSTMENOPAUSAL WOMEN: RELATIONSHIP WITH ESTRADIOL CONCENTRATIONS

    PubMed Central

    Pop, L. Claudia; Shapses, Sue A.; Chang, Brian; Sun, Wei; Wang, Xiangbing

    2016-01-01

    Objective To examine the relationship between endogenous serum estradiol and vitamin D–binding protein (DBP) and total, free, and bioavailable 25-hydroxyvitamin D (25OHD) concentrations in pre- and postmenopausal women. Methods In 165 healthy women (ages, 26 to 75 years) not taking any form of exogenous estrogen, the serum concentrations of estradiol, 25OHD, DBP, parathyroid hormone, and albumin were measured. Free and bioavailable 25OHD (free + albumin-bound) levels were calculated from total 25OHD, DBP, and serum albumin levels. Results Premenopausal women had higher serum 25OHD (31.5 ± 7.9 ng/mL), DBP (45.3 ± 6.2 mg/dL), and estradiol (52.8 ± 35.0 pg/mL) levels than postmenopausal women (26.5 ± 4.9 ng/mL, 41.7 ± 5.7 mg/dL, and 12.9 ± 4.9 pg/mL), respectively. In addition, the calculated free and bioavailable 25OHD levels were higher in pre- than postmenopausal women (P<.05). Serum estradiol correlated with DBP (r = 0.22; P<.01) and total 25OHD (r = 0.27; P<.01). In multivariate regression models (with or without serum 25OHD), estradiol was independently associated with DBP (P<.05). Conclusion Lower estradiol level is one of the factors that contribute to lower DBP levels in older women. Our data indicate that besides well-known factors such as age, gender, and race, serum estradiol concentrations are also a physiologic predictor of DBP concentration. PMID:26121448

  6. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats.

    PubMed

    Souza, M F; Couto-Pereira, N S; Freese, L; Costa, P A; Caletti, G; Bisognin, K M; Nin, M S; Gomez, R; Barros, H M T

    2014-06-01

    Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

  7. Comparison of Two Methods of Estradiol Replacement: their Physiological and Behavioral Outcomes

    PubMed Central

    Mosquera, Laurivette; Shepherd, Luz; Torrado, Aranza I; Torres-Diaz, Yvonne M; Miranda, Jorge D; Segarra, Annabell C

    2016-01-01

    Fluctuating sex steroids during the estrous or menstrual cycle of mammalian females make it difficult to determine their role on behaviors and physiology. To avoid this, many investigators ovariectomize their animals and administer progesterone, estradiol or a combination of both. Several different strategies are used to administer estradiol, which confounds interpretation of results. This study compared two methods of estradiol replacement implants: Silastic tubes filled with crystalline estradiol benzoate (E2) and commercially available estradiol benzoate pellets. Implants were placed subcutaneously in adult ovariectomized (OVX) rats and blood samples obtained weekly. Control OVX rats received empty Silastic tubes or placebo pellets. Our data shows that E2 plasma levels from rats with Silastic implants peaked after one week and decreased slowly thereafter. In contrast, plasma E2 from commercial pellets peaked after two weeks, increasing and decreasing over time. To validate hormone release, body weight was monitored. All E2 treated animals maintained a similar body weight over the four weeks period whereas an increase in body weight over time was observed in the OVX group that received empty implants, confirming E2 release and supporting the role of E2 in the regulation of body weight. Furthermore, the effects of E2 on basal locomotor activity were assessed using animal activity cages. Results showed no difference between E2 and control group in several locomotor activities. These results indicate that Silastic implants achieve more stable plasma estradiol levels than pellets and thus are a better alternative for studies of estradiol on brain function and behavior. PMID:26962471

  8. Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle.

    PubMed

    Albert, Kimberly; Pruessner, Jens; Newhouse, Paul

    2015-09-01

    Although ovarian hormones are thought to have a potential role in the well-known sex difference in mood and anxiety disorders, the mechanisms through which ovarian hormone changes contribute to stress regulation are not well understood. One mechanism by which ovarian hormones might impact mood regulation is by mediating the effect of psychosocial stress, which often precedes depressive episodes and may have mood consequences that are particularly relevant in women. In the current study, brain activity and mood response to psychosocial stress was examined in healthy, normally cycling women at either the high or low estradiol phase of the menstrual cycle. Twenty eight women were exposed to the Montreal Imaging Stress Task (MIST), with brain activity determined through functional magnetic resonance imaging, and behavioral response assessed with subjective mood and stress measures. Brain activity responses to psychosocial stress differed between women in the low versus high estrogen phase of the menstrual cycle: women with high estradiol levels showed significantly less deactivation in limbic regions during psychosocial stress compared to women with low estradiol levels. Additionally, women with higher estradiol levels also had less subjective distress in response to the MIST than women with lower estradiol levels. The results of this study suggest that, in normally cycling premenopausal women, high estradiol levels attenuate the brain activation changes and negative mood response to psychosocial stress. Normal ovarian hormone fluctuations may alter the impact of psychosocially stressful events by presenting periods of increased vulnerability to psychosocial stress during low estradiol phases of the menstrual cycle. This menstrual cycle-related fluctuation in stress vulnerability may be relevant to the greater risk for affective disorder or post-traumatic stress disorder in women.

  9. The normal breast epithelium of women with breast cancer displays an aberrant response to estradiol.

    PubMed

    Khan, S A; Sachdeva, A; Naim, S; Meguid, M M; Marx, W; Simon, H; Halverson, J D; Numann, P J

    1999-10-01

    Breast epithelial response to estradiol may play an important role in breast cancer etiology. We have examined the relationship between serum estradiol and progesterone levels and normal breast epithelial expression of estrogen receptor (ER) alpha, progesterone receptor (PgR), and epithelial proliferation (as reflected by the Ki-67 labeling index) in 121 women (50 newly diagnosed breast cancer cases and 71 benign breast disease controls). Simultaneous samples of grossly normal breast tissue and venous blood were obtained from women undergoing breast surgery. Serum estradiol and progesterone levels were measured by radioimmunoassay; breast epithelial ER, PgR, and Ki-67 expression was measured by immunohistochemistry. Linear regression, controlled for patient age and ductal and lobular composition of the tissue, showed that the breast epithelium of control women displayed an inverse correlation between serum estradiol and ER-alpha, which was not seen in case women (P for the difference in regression slopes = 0.001). PgR expression displayed a significant positive correlation with serum estradiol in cases, but not in controls. Epithelial proliferation had no relationship to either estradiol or progesterone in both cases and controls but showed an inverse relationship with ER in controls and a direct relationship in cases (P for the difference in regression slopes = 0.066). These results suggest a dysregulation of hormonal response in the normal breast epithelium of high-risk women, with lack of regulation of ER by estradiol, increased estrogen responsiveness as reflected by PgR expression, and a dissociation of ER expression and proliferative response.

  10. Low Doses of 17β-Estradiol Rapidly Improve Learning and Increase Hippocampal Dendritic Spines

    PubMed Central

    Phan, Anna; Gabor, Christopher S; Favaro, Kayla J; Kaschack, Shayna; Armstrong, John N; MacLusky, Neil J; Choleris, Elena

    2012-01-01

    While a great deal of research has been performed on the long-term genomic actions of estrogens, their rapid effects and implications for learning and memory are less well characterized. The often conflicting results of estrogenic effects on learning and memory may be due to complex and little understood interactions between genomic and rapid effects. Here, we investigated the effects of low, physiologically relevant, doses of 17β-estradiol on three different learning paradigms that assess social and non-social aspects of recognition memory and spatial memory, during a transcription independent period of memory maintenance. Ovariectomized female CD1 mice were subcutaneously administered vehicle, 1.5 μg/kg, 2 μg/kg, or 3 μg/kg of 17β-estradiol 15 minutes before social recognition, object recognition, or object placement learning. These paradigms were designed to allow the testing of learning effects within 40 min of hormone administration. In addition, using a different set of ovariectomized mice, we examined the rapid effects of 1.5 μg/kg, 2 μg/kg, or 3 μg/kg of 17β-estradiol on CA1 hippocampal dendritic spines. All 17β-estradiol doses tested impacted learning, memory, and CA1 hippocampal spines. 17β-Estradiol improved both social and object recognition, and may facilitate object placement learning and memory. In addition, 17β-estradiol increased dendritic spine density in the stratum radiatum subregion of the CA1 hippocampus, but did not affect dendritic spines in the lacunosum-moleculare, within 40 min of administration. These results demonstrate that the rapid actions of 17β-estradiol have important implications for general learning and memory processes that are not specific for a particular type of learning paradigm. These effects may be mediated by the rapid formation of new dendritic spines in the hippocampus. PMID:22669167

  11. Estradiol-induced gene expression in largemouth bass (Micropterus salmoides)

    USGS Publications Warehouse

    Bowman, C.J.; Kroll, K.J.; Gross, T.G.; Denslow, N.D.

    2002-01-01

    Vitellogenin (Vtg) and estrogen receptor (ER) gene expression levels were measured in largemouth bass to evaluate the activation of the ER-mediated pathway by estradiol (E2). Single injections of E2 ranging from 0.0005 to 5 mg/kg up-regulated plasma Vtg in a dose-dependent manner. Vtg and ER mRNAs were measured using partial cDNA sequences corresponding to the C-terminal domain for Vtg and the ligand-binding domain of ER?? sequences. After acute E2-exposures (2 mg/kg), Vtg and ER mRNAs and plasma Vtg levels peaked after 2 days. The rate of ER mRNA accumulation peaked 36-42 h earlier than Vtg mRNA. The expression window for ER defines the primary response to E2 in largemouth bass and that for Vtg a delayed primary response. The specific effect of E2 on other estrogen-regulated genes was tested during these same time windows using differential display RT-PCR. Specific up-regulated genes that are expressed in the same time window as Vtg were ERp72 (a membrane-bound disulfide isomerase) and a gene with homology to an expressed gene identified in zebrafish. Genes that were expressed in a pattern that mimics the ER include the gene for zona radiata protein ZP2, and a gene with homology to an expressed gene found in winter flounder. One gene for fibrinogen ?? was down-regulated and an unidentified gene was transiently up-regulated after 12 h of exposure and returned to basal levels by 48 h. Taken together these studies indicate that the acute molecular response to E2 involves a complex network of responses over time. ?? 2002 Elsevier Science Ireland Ltd. All rights reserved.

  12. Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells.

    PubMed

    Masamura, S; Santner, S J; Heitjan, D F; Santen, R J

    1995-10-01

    Genetic and environmental factors can modulate the level of sensitivity to various hormones, including estrogens. Enhanced sensitivity to estradiol (E2) has been demonstrated in several biological conditions, such as in sheep during the nonbreeding season, in untreated patients with Turner's syndrome, and in the prepubertal state in normal girls. We postulated that secondary responses to hormonal therapy in patients with breast cancer could also result from enhanced E2 sensitivity, developing as an adaptive mechanism to E2 deprivation. The present study used the MCF-7 human breast cancer cell line as a model system to test the concept that enhanced sensitivity to E2 may occur as a result of adaptation to low E2 levels. After depriving MCF-7 cells of estrogens in tissue culture medium for periods of 1-6 months, we established conditions under which replication could be stimulated maximally by 10(-14)-10(-15) mol/L E2. In contrast, wild-type cells not exposed to estrogen deprivation required 10(-10) mol/L E2 to grow at the same rate. Further, the concentration of the antiestrogen, ICI 164384, needed to inhibit growth by 50% in estrogen-deprived cells was much lower than that required in wild-type cells (i.e. 10(-15) vs. 10(-9) mol/L). Nude mice implanted with these estrogen-deprived cells demonstrated an earlier appearance of palpable tumors in response to E2 than animals bearing wild-type cells. Reexposure to 10(-10)-10(-9) mol/L E2, either in vivo or in vitro, returned these cells to the level of estrogen sensitivity observed in wild-type cells. Taken together, these observations suggest that breast cancer cells can adapt to low levels of estrogens by enhancing their sensitivity to E2.

  13. Transdermal Estradiol Treatment for Postpartum Depression: A Pilot Randomized Trial

    PubMed Central

    Wisner, Katherine L.; Sit, Dorothy K.Y.; Moses-Kolko, Eydie L.; Driscoll, Kara E.; Prairie, Beth; Stika, Catherine S.; Eng, Heather F.; Dills, John L; Luther, James F.; Wisniewski, Stephen R.

    2015-01-01

    Postpartum depression occurs in 14.5% of women in the first three months after birth. This study was an 8 week acute phase randomized trial with three cells (transdermal estradiol (E2), sertraline, and placebo) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than pre-study projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were: 1) Study patch non-adhesion, which did not explain the low concentrations across the entire sample. 2) Ineffective transdermal patch preparations, although two different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. 3) Obesity, at study entry, E2-treated women had mean ± SD BMI=32.9 ±7.4. No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women vs. normal weight controls are available. 4) Induction of Cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and Phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 mcg/day did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing. PMID:26061609

  14. Transdermal Estradiol Treatment for Postpartum Depression: A Pilot, Randomized Trial.

    PubMed

    Wisner, Katherine L; Sit, Dorothy K Y; Moses-Kolko, Eydie L; Driscoll, Kara E; Prairie, Beth A; Stika, Catherine S; Eng, Heather F; Dills, John L; Luther, James F; Wisniewski, Stephen R

    2015-08-01

    Postpartum depression occurs in 14.5% of women in the first 3 months after birth. This study was an 8-week acute phase randomized trial with 3 cells (transdermal estradiol [E2], sertraline [SERT], and placebo [PL]) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than prestudy projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were as follows: (1) study patch nonadhesion, which did not explain the low concentrations across the entire sample. (2) Ineffective transdermal patch preparations, although 2 different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. (3) Obesity, at study entry, E2-treated women had body mass index of 32.9 (7.4) (mean [SD]). No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women versus normal weight controls are available. (4) Induction of cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 μg/d did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing. PMID:26061609

  15. Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus

    NASA Technical Reports Server (NTRS)

    Krumenacker, J. S.; Hyder, S. M.; Murad, F.

    2001-01-01

    Previous reports that investigated the regulation of the NO/soluble guanylyl cyclase (sGC)/cGMP pathway by estrogenic compounds have focused primarily on the levels of NO, NO-producing enzymes, and cGMP in various tissues. In this study, we demonstrate that 17beta-estradiol (E2) regulates the alpha(1) and beta(1) subunits of the NO receptor, sGC, at the mRNA and protein levels in rat uterus. Using real-time quantitative PCR, we found that within 1 h of in vivo E2 administration to rats, sGC mRNA levels begin to diminish. After 3 h, there is a maximal diminution of sGC mRNA expression (sGC alpha(1) 10% and sGC beta(1) 33% of untreated). This effect was blocked by the estrogen receptor antagonist, ICI 182,780, indicating that estrogen receptor is required. The effect of E2 also was observed in vitro with incubations of uterine tissue, indicating that the response does not depend on the secondary release of other hormones or factors from other tissues. Puromycin did not block the effect, suggesting the effects occur because of preexisting factors in uterine tissues and do not require new protein synthesis. Using immunoblot analysis, we found that sGC protein levels also were reduced by E2 over a similar time course as the sGC mRNA. We conclude that sGC plays a vital role in the NO/sGC/cGMP regulatory pathway during conditions of elevated estrogen levels in the rat uterus as a result of the reduction of sGC expression.

  16. Tracking polychlorinated biphenyls (PCBs) congener patterns in Newark Bay surface sediment using principal component analysis (PCA) and positive matrix factorization (PMF).

    PubMed

    Saba, Tarek; Su, Steave

    2013-09-15

    PCB congener data for Newark Bay surface sediments were analyzed using PCA and PMF, and relationships between the outcomes from these two techniques were explored. The PCA scores plot separated the Lower Passaic River Mouth samples from North Newark Bay, thus indicating dissimilarity. Although PCA was able to identify subareas in the Bay system with specific PCB congener patterns (e.g., higher chlorinated congeners in Elizabeth River), further conclusions reading potential PCB source profiles or potential upland source areas were not clear for the PCA scores plot. PMF identified five source factors, and explained the Bay sample congener profiles as a mix of these Factors. This PMF solution was equivalent to (1) defining an envelope that encompasses all samples on the PCA scores plot, (2) defining source factors that plot on that envelope, and (3) explaining the congener profile for each Bay sediment sample (inside the scores plot envelope) as a mix of factors. PMF analysis allowed identifying characteristic features in the source factor congener distributions that allowed tracking of source factors to shoreline areas where PCB inputs to the Bay may have originated. The combined analysis from PCA and PMF showed that direct discharges to the Bay are likely the dominant sources of PCBs to the sediment. Review of historical upland activities and regulatory files will be needed, in addition to the PCA and PMF analysis, to fully reconstruct the history of operations and PCB releases around the Newark Bay area that impacted the Bay sediment. PMID:23831929

  17. Differential action of decidual luteotropin on luteal and follicular production of testosterone and estradiol.

    PubMed

    Gibori, G; Kalison, B; Warshaw, M L; Basuray, R; Glaser, L A

    1985-05-01

    Decidual tissue of the rat produces a hormone with physiological and biochemical characteristics similar to those of PRL. Because PRL affects both follicular and luteal production of testosterone and estradiol, it was of interest to determine whether decidual luteotropin affects basal and/or LH-stimulated ovarian secretion of steroids and whether it differentially affects follicular and luteal synthesis of testosterone and estradiol. The uteri of pseudopregnant adult rats were scratched on day 5 to induce decidual tissue formation. Pseudopregnant animals without decidua were used as controls. Rats were either hypophysectomized on day 8 or left intact. They were treated with 1.5 IU hCG/day or with vehicle between days 8-9. On day 9, blood was obtained from the ovarian vein, and both corpora lutea and large antral follicles were isolated and incubated in vitro. The presence of the decidua significantly suppressed both basal and hCG-stimulated ovarian secretion of estradiol, yet enhanced progesterone production. A similar inhibitory effect of decidual tissue on hCG stimulation of testosterone and estradiol was observed in the hypophysectomized rats. When the effect of decidua on follicles and corpora lutea was studied separately, it was found that follicles of rats with decidua produced significantly less testosterone and estradiol than follicles of rats without decidua. hCG administration to either intact or hypophysectomized rats markedly enhanced the follicular capacity to produce these two steroids. However, the degree of hCG stimulation of follicular steroidogenesis was significantly reduced by the presence of decidual tissue. In contrast, the decidua did not inhibit the in vitro steroidogenic capacity of corpora lutea. Luteal tissue of intact rats with or without decidua produced similar basal amounts of testosterone and estradiol and responded to a hCG challenge with comparable increases in the production of both steroids. After hypophysectomy, however, the

  18. Effects of various doses of estradiol on chlamydial genital infection in ovariectomized guinea pigs.

    PubMed

    Pasley, J N; Rank, R G; Hough, A J; Cohen, C; Barron, A L

    1985-01-01

    The effect of various doses of estradiol on genital tract infection by the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC) was investigated in ovariectomized guinea pigs. Prolongation of infection, as determined by chlamydial inclusion counts of cells in Giemsa-stained smears of vaginal scrapings, was observed in animals receiving daily doses of 1.0, 10.0, 100.0, or 1000 micrograms of estradiol. In contrast to controls, ascending infection resulting in endometritis was found in animals receiving doses of greater than or equal to 1.0 microgram of estradiol per day. Response to estradiol treatment was reflected in an increase in cervical-uterine wet weight and uterine wall thickness. No differences were observed in time of appearance of antibody titers to GPIC in serum, but a delay in appearance of IgA antibody to GPIC in genital secretions was found in estradiol-treated animals receiving doses of greater than or equal to 1.0 microgram per day.

  19. Tissue responsiveness to estradiol and genistein in the sea bass liver and scale.

    PubMed

    Pinto, Patrícia I S; Estêvão, M Dulce; Andrade, André; Santos, Soraia; Power, Deborah M

    2016-04-01

    As in mammals, estrogens in fish are essential for reproduction but also important regulators of mineral homeostasis. Fish scales are a non-conventional target tissue responsive to estradiol and constitute a good model to study mineralized tissues effects and mechanisms of action of estrogenic compounds, including phytoestrogens. The responsiveness to estradiol and the phytoestrogen genistein, was compared between the scales and the liver, a classical estrogenic target, in sea bass (Dicentrarchus labrax). Injection with estradiol and genistein significantly increased circulating vitellogenin (for both compounds) and mineral levels (estradiol only) and genistein also significantly increased scale enzymatic activities suggesting it increased mineral turnover. The repertoire, abundance and estrogenic regulation of nuclear estrogen receptors (ESR1, 2a and 2b) and membrane G-protein receptors (GPER and GPER-like) were different between liver and scales, which presumably explains the tissue-specific changes detected in estrogen-responsive gene expression. In scales changes in gene expression mainly consisted of small rapid increases, while in liver strong, sustained increases/decreases in gene expression occurred. Similar but not overlapping gene expression changes were observed in response to both estradiol and genistein. This study demonstrates for the first time the expression of membrane estrogen receptors in scales and that estrogens and phytoestrogens, to which fish may be exposed in the wild or in aquaculture, both affect liver and mineralized tissues in a tissue-specific manner. PMID:26718875

  20. Intranasal estradiol: new formulation. Intranasal oestrogen delivery system: just a gimmick.

    PubMed

    2002-12-01

    (1) Many oral and transdermal (patch and gel) estradiol preparations are already available for controlling menopausal symptoms due to oestrogen deficiency. (2) Marketing authorization has now been granted in Europe for an intranasal delivery system, which produces a high, brief plasma estradiol peak. (3) According to two clinical trials, the symptomatic effects of 300 micrograms of estradiol daily by the intranasal route is similar to that of 50 micrograms /day transdermally (unblinded trial) and 2 mg/day orally (double-blind trial). (4) The most frequent side effects are intranasal reactions (in approximately 50% of patients), breast pain (30-40% of patients), and metrorrhagia (approximately 7% of cycles). (5) The long-term consequences of such high plasma estradiol peaks, including the risk of breast cancer, are unknown. (6) Intranasal estradiol is not reimbursed in France, unlike other oestrogen preparations for use in menopausal women. (7) In practice, oral and transdermal delivery systems, with which we have lengthy experience, are adequate for relieving menopausal symptoms. The intranasal route offers no proven advantage, and its long-term risks are unknown.

  1. Estradiol worsens the syndrome of ischemia-reperfusion injury in an experimental lung transplantation model.

    PubMed

    Santana-Rodríguez, Norberto; Clavo, Bernardino; Llontop, Pedro; López, Ana; García-Castellano, José Manuel; Machín, Rubén P; Ponce, Miguel A; Fiuza, María D; García-Herrera, Ricardo; Brito, Yanira; Yordi, Nagib Atallah; Chirino, Ricardo

    2011-06-01

    Ischemia-reperfusion injury (IRI) is a common complication after lung transplantation. There is evidence that reactive oxygen species are involved in its pathogenesis. We designed an experimental study to evaluate whether the administration of antioxidants to lung transplantation recipients protects against IRI and early acute rejection (AR). Twenty-five rats received left lung transplants after 6 h of ischemia. Fifty minutes before the reperfusion, groups of five rats received a single dose of desferrioxamine (20 mg/kg), estradiol (25 mg/kg), or melatonin (10 mg/kg). The animals were killed 48 h after surgery and the postoperative outcome, IRI, and AR were evaluated. The frequency of severe injury and of moderate-to-severe edema was higher in animals treated with estradiol than in the control group (P = 0.022 and P = 0.026, respectively). No significant changes in the degree of IRI or AR were observed in the groups treated with desferrioxamine or melatonin. In our study, treatment with the antioxidants melatonin or desferrioxamine before reperfusion had no effects on IRI damage or on AR frequency or severity. However, treatment with estradiol resulted in a worse postoperative outcome and in severe edema. Therefore, despite the antioxidant capacity of estradiol, it is recommended that an evaluation of these adverse effects of estradiol in human lung transplant recipients be performed.

  2. Testosterone metabolism in human skin cells in vitro and its interaction with estradiol and dutasteride.

    PubMed

    Münster, U; Hammer, S; Blume-Peytavi, U; Schäfer-Korting, M

    2003-01-01

    Since the limited knowledge of cutaneous drug metabolism can impair the development of specifically acting topical dermatics and transdermal application systems, the cell-type-specific androgen metabolism in human skin and its inhibition by drugs were investigated. Cultured human foreskin and scalp skin keratinocytes and fibroblasts as well as occipital scalp dermal papilla cells (DPC) were incubated with testosterone 10(-6) and 10(-8)M alone and in the presence of 17alpha-estradiol, 17beta-estradiol or dutasteride for 24 h. Androgens extracted from culture supernatants were subjected to thin-layer chromatography and quantified by beta-counting. In keratinocytes and DPC, dihydrotestosterone (DHT) was only formed to a low extent while androstenedione was the main metabolite. In fibroblasts, DHT formation was pronounced following 10(-8)M testosterone. Dutasteride 10(-8)M completely suppressed 5alpha-dihydro metabolite formation. 17alpha-Estradiol and 17beta-estradiol at nontoxic concentrations decreased 17-ketometabolites. Human skin regulates testosterone action by cell-type-specific activation or deactivation. Effects of 17alpha-estradiol in androgenetic alopecia are not due to 5alpha-reductase inhibition. Dutasteride may be useful in acne and androgenetic alopecia. PMID:14528059

  3. Effects of high and low 17β-estradiol doses on focal cerebral ischemia in rats

    PubMed Central

    Ingberg, Edvin; Theodorsson, Elvar; Theodorsson, Annette; Ström, Jakob O.

    2016-01-01

    The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17β-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se, and not the route and method of administration, that determines the effect, and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n = 40 per group) were randomized into three groups, subcutaneously administered different doses of 17β-estradiol and subjected to transient middle cerebral artery occlusion. The modified sticky tape test was performed after 24 h and the rats were subsequently sacrificed for infarct size measurements. In contrast to our hypothesis, a significant negative correlation between 17β-estradiol dose and infarct size was found (p = 0.018). Thus, no support was found for the hypothesis that 17β-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the findings indicate that the higher the dose of 17β-estradiol, the smaller the infarct. PMID:26839007

  4. Ovariectomy and 17β-estradiol replacement in rats and mice: a visual demonstration.

    PubMed

    Ström, Jakob O; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

    2012-01-01

    Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures. PMID:22710371

  5. Ovariectomy and 17β-estradiol Replacement in Rats and Mice: A Visual Demonstration

    PubMed Central

    Ström, Jakob O.; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

    2012-01-01

    Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results1-3. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol4-6. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration7, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures. PMID:22710371

  6. Acquisition of cocaine self-administration in ovariectomized female rats: Effect of estradiol dose or chronic estradiol administration

    PubMed Central

    Hu, Ming; Becker, Jill B.

    2008-01-01

    This study was conducted to investigate whether the dose of estradiol (E) administered acutely, or chronic delivery of one dose of E impacts acquisition and subsequent cocaine self-administration in ovariectomized (OVX) female rats. Five groups of female rats were compared: OVX females treated with 0, 1, 2, or 5 µg 17 β-E, 30 min prior to the self-administration session, and OVX rats that received a 1.5 mg E pellet (designed to chronically release 25 µg E/d X 60 d) implanted 1 week before cocaine self-administration initiation. Rats were tested in 1 hr sessions on a FR1 schedule with the dose of cocaine increasing every week (testing occurred 5 day/wk; doses: 0.2, 0.3, 0.4, 0.5 and 0.75 mg/kg/infusion). We report that OVX rats treated with 2 µg E acquired self-administration more rapidly than all of the other groups, and animals that received 1 or 2 µg E self-administered significantly more cocaine compared to OVX+vehicle at 0.3 and 0.4 mg/kg/infusion. In contrast, OVX rats given 5 µg E acutely, or chronic E via slow-release pellets did not take more cocaine than the OVX+vehicle group at any time point. Physiological serum concentrations of E were seen with 1 or 2 µg E, but 5 µg E and the E pellet produced supra-physiological concentrations. These results suggest an inverted U-shaped dose-response curve for the effect of E on acquisition of cocaine self-administration. PMID:18054446

  7. Behavior and survival of Mytilus congeners following episodes of elevated body temperature in air and seawater.

    PubMed

    Dowd, W Wesley; Somero, George N

    2013-02-01

    Coping with environmental stress may involve combinations of behavioral and physiological responses. We examined potential interactions between adult mussels' simple behavioral repertoire - opening/closing of the shell valves - and thermal stress physiology in common-gardened individuals of three Mytilus congeners found on the West Coast of North America: two native species (M. californianus and M. trossulus) and one invasive species from the Mediterranean (M. galloprovincialis). We first continuously monitored valve behavior over three consecutive days on which body temperatures were gradually increased, either in air or in seawater. A temperature threshold effect was evident between 25 and 33°C in several behavioral measures. Mussels tended to spend much less time with the valves in a sealed position following exposure to 33°C body temperature, especially when exposed in air. This behavior could not be explained by decreases in adductor muscle glycogen (stores of this metabolic fuel actually increased in some scenarios), impacts of forced valve sealing on long-term survival (none observed in a second experiment), or loss of contractile function in the adductor muscles (individuals exhibited as many or more valve adduction movements following elevated body temperature compared with controls). We hypothesize that this reduced propensity to seal the valves following thermal extremes represents avoidance of hypoxia-reoxygenation cycles and concomitant oxidative stress. We further conjecture that prolonged valve gaping following episodes of elevated body temperature may have important ecological consequences by affecting species interactions. We then examined survival over a 90 day period following exposure to elevated body temperature and/or emersion, observing ongoing mortality throughout this monitoring period. Survival varied significantly among species (M. trossulus had the lowest survival) and among experimental contexts (survival was lowest after experiencing

  8. Bioavailability of phthalate congeners to earthworms (Eisenia fetida) in artificially contaminated soils.

    PubMed

    Hu, Xiao-yu; Wen, Bei; Zhang, Shuzhen; Shan, Xiao-quan

    2005-09-01

    Bioavailability of phthalate congeners, dimethyl phthalate, diethyl phthalate, di-n-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), and dioctyl phthalate, to earthworms (Eisenia fetida) were studied when earthworms were exposed to two artificially contaminated agricultural and forest soils. Only DBP and DEHP were detected in earthworms. The uptake kinetics of DBP and DEHP in earthworms was fast within the initial 10 days followed by a nearly steady state for the subsequent 20 days. An equilibrium partitioning model could be used to describe the uptake kinetics of DBP and DEHP by earthworm in two types of soils (r = 0.709-0.864). The average biota-to-soil accumulation factors (BSAFs) of DBP and DEHP at 5 mg kg(-1) in soil were 0.27 +/- 0.07 and 0.17 +/- 0.03, respectively, in agricultural soil, while the BSAFs were 0.21 +/- 0.06 and 0.07 +/- 0.02, respectively, in forest soil. The concentrations of phthalates in earthworms increased with increasing concentrations of phthalates in soil. There was a significant correlation between logC(soil) and logC(worm), with r = 0.999-0.993, demonstrating a single linear partitioning of phthalates between soil and earthworms. The bioavailability of DBP and DEHP was assessed by Soxhlet, methanol, and methanol-water (1:1) extraction methods. Our results indicated that the extractable amounts of freshly added DBP and DEHP in soils by these extraction methods were significantly correlated with those in earthworms. It was observed that the extractable DBP and DEHP by the methanol and methanol-water (1:1) extraction methods decreased with their increasing residence time in soil. In contrast, the amount extracted by the Soxhlet extraction method did not show a similar decline. Therefore, Soxhlet extraction was a poor indicator of the bioavailability of DBP and DEHP to earthworms in soil, which could lead to overestimation of the risk of soil-associated DBP and DEHP. The extractable DBP and DEHP by methanol and methanol

  9. Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells.

    PubMed Central

    Migliaccio, A; Di Domenico, M; Castoria, G; de Falco, A; Bontempo, P; Nola, E; Auricchio, F

    1996-01-01

    The mechanism by which estradiol acts on cell multiplication is still unclear. Under conditions of estradiol-dependent growth, estradiol treatment of human mammary cancer MCF-7 cells triggers rapid and transient activation of the mitogen-activated (MAP) kinases, erk-1 and erk-2, increases the active form of p21ras, tyrosine phosphorylation of Shc and p190 protein and induces association of p190 to p21ras-GAP. Both Shc and p190 are substrates of activated src and once phosphorylated, they interact with other proteins and upregulate p21ras. Estradiol activates the tyrosine kinase/p21ras/MAP-kinase pathway in MCF-7 cells with kinetics which are similar to those of peptide mitogens. It is only after introduction of the human wild-type 67 kDa estradiol receptor cDNA that Cos cells become estradiol-responsive in terms of erk-2 activity. This finding, together with the inhibition by the pure anti-estrogen ICI 182 780 of the stimulatory effect of estradiol on each step of the pathway in MCF-7 cells proves that the classic estradiol receptor is responsible for the transduction pathway activation. Transfection experiments of Cos cells with the estradiol receptor cDNA and in vitro experiments with c-src show that the estradiol receptor activates c-src and this activation requires occupancy of the receptor by hormone. Our experiments suggest that c-src is an initial and integral part of the signaling events mediated by the estradiol receptor. Images PMID:8635462

  10. Regulation of energy expenditure by estradiol in premenopausal women.

    PubMed

    Melanson, Edward L; Gavin, Kathleen M; Shea, Karen L; Wolfe, Pamela; Wierman, Margaret E; Schwartz, Robert S; Kohrt, Wendy M

    2015-11-01

    Suppressing sex hormones in women for 1 wk reduces resting energy expenditure (REE). The effects of more chronic suppression on REE and other components of total energy expenditure (TEE), and whether the reduction in REE is specifically due to loss of estradiol (E2), are not known. We compared the effects of 5 mo of sex hormone suppression (gonadotropin releasing hormone agonist therapy, GnRHAG) with placebo (PL) or E2 add-back therapy on REE and the components of TEE. Premenopausal women received GnRHAG (leuprolide acetate 3.75 mg/mo) and were randomized to receive transdermal therapy that was either E2 (0.075 mg/d; n = 24; means ± SD, aged = 37 ± 8 yr, BMI = 27.3 ± 6.2 kg/m(2)) or placebo (n = 21; aged = 34 ± 9 yr, BMI = 26.8 ± 6.2 kg/m(2)). REE was measured by using a metabolic cart, and TEE, sleep EE (SEE), exercise EE (ExEE, 2 × 30 min bench stepping), non-Ex EE (NExEE), and the thermic effect of feeding (TEF) were measured by using whole room indirect calorimetry. REE decreased in GnRHAG+PL [mean (95% CI), -54 (-98, -15) kcal/d], but not GnRHAG+E2 [+6 (-33, +45) kcal/d] (difference in between-group changes, P < 0.05). TEE decreased in GnRHAG+PL [-128 (-214, -41) kcal/d] and GnRHAG+E2 [-96 (-159, -32) kcal/d], with no significant difference in between-group changes (P = 0.55). SEE decreased similarly in both GnRHAG+PL [-0.07 (-0.12, -0.03) kcal/min] and GnRHAG+E2 [-0.07 (-0.12, -0.02) kcal/min]. ExEE decreased in GnRHAG+PL [-0.46 (-0.79, -0.13) kcal/min], but not GnRHAG+E2 [-0.30 (-0.65, +0.06) kcal/min]. There were no changes in TEF or NExEE in either group. In summary, chronic pharmacologic suppression of sex hormones reduced REE and this was prevented by E2 therapy.

  11. 5alpha-Reduced androgens block estradiol-BSA-stimulated release of oxytocin.

    PubMed

    Caldwell, Jack D; Song, Yan; Englöf, Ila; Höfle, Simone; Key, Mary; Morris, Mariana

    2003-06-27

    In this study we test the postulate that estradiol conjugated to bovine serum albumin (E-BSA) acts via receptors for the steroid-binding protein sex hormone binding globulin (SHBG) by attempting to block E-BSA-stimulated release of oxytocin with two antagonists of SHBG receptor actions: the 5alpha-reduced androgens dihydrotestosterone (DHT) and 3alpha-diol. Simultaneous superfusion with either DHT or 3alpha-diol significantly blocked E-BSA-stimulated release of oxytocin. We also found that a wide range of free 17beta-estradiol was unable to stimulate oxytocin release, suggesting that E-BSA stimulates receptors other than those for free estradiol to release oxytocin, perhaps SHBG receptors.

  12. The positive feedback of estradiol on gonadotropin secretion in women with perimenopausal dysfunctional uterine bleeding.

    PubMed

    Cano, A; Gimeno, F; Fuente, T; Parrilla, J J; Abad, L

    1986-09-01

    The functionality of the hypothalamic-pituitary-ovarian axis was explored in 27 women with perimenopausal dysfunctional uterine bleeding. The positive feedback effect of estradiol on LH and FSH was studied by the estrogen challenge test, which was performed by a single i.m. injection of estradiol benzoate. An early decline of both LH and FSH was followed by an increase of LH, mainly due to the cases in which the estrogen test was positive. FSH remained low through the whole period tested. The results were compared with those found in 5 normal menstruating women. The frequency of positive estrogen tests, defined by an acute estradiol-induced discharge of LH, was lower in the perimenopausal patients (P less than 0.025). The results of the tests used in our study showed an impairment of the positive feedback system in the perimenopausal-dysfunctional-bleeding group.

  13. Effects of 17β-estradiol on emissions of greenhouse gases in simulative natural water body.

    PubMed

    Ruan, Aidong; Zhao, Ying; Liu, Chenxiao; Zong, Fengjiao; Yu, Zhongbo

    2015-05-01

    Environmental estrogens are widely spread across the world and are increasingly thought of as serious contaminators. The present study looks at the influence of different concentrations of 17β-estradiol on greenhouse gas emissions (CO2 , CH4 , and N2 O) in simulated systems to explore the relationship between environmental estrogen-pollution and greenhouse gas emissions in natural water bodies. The present study finds that 17β-estradiol pollution in simulated systems has significant promoting effects on the emissions of CH4 and CO2 , although no significant effects on N2 O emissions. The present study indicates that 17β-estradiol has different effects on the different elements cycles; the mechanism of microbial ecology is under review.

  14. OXIDATION OF POLYCHLORINATED BIPHENYLS BY LIVER TISSUE SLICES FROM PHENOBARBITAL-PRETREATED MICE IS CONGENER-SPECIFIC AND ATROPSELECTIVE

    PubMed Central

    Wu, Xianai; Duffel, Michael; Lehmler, Hans-Joachim

    2013-01-01

    Mouse models are powerful tools to study the developmental neurotoxicity of polychlorinated biphenyls (PCBs); however, studies of the oxidation of chiral PCB congeners to potentially neurotoxic hydroxylated metabolites (OH-PCBs) in mice have not been reported. Here we investigate the atropselective oxidation of chiral PCB 91 (2,2',3,4',6-pentachlorobiphenyl), PCB 95 (2,2',3,5',6-pentachlorobiphenyl), PCB 132 (2,2',3,3',4,6'-hexachlorobiphenyl), PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl) and PCB 149 (2,2',3,4',5',6-hexachlorobiphenyl) to OH-PCBs in liver tissue slices prepared from female mice. The metabolite profile of PCB 136 typically followed the rank order 5-OH-PCB > 4-OH-PCB > 4,5-OH-PCB, and metabolite levels increased with PCB concentration and incubation time. A similar OH-PCB profile was observed with the other PCB congeners, with 5-OH-PCB:4-OH-PCB ratios ranging from 2 to 12. More 5-OH-PCB 136 was formed in liver tissue slices obtained from animals pretreated with phenobarbital (P450 2B inducer) or, to a lesser extent, dexamethasone (P450 2B and 3A enzyme inducer) compared to tissue slices prepared from vehicle-pretreated animals. The apparent rate of 5-OH-PCBs formation followed the approximate rank order PCB 149 > PCB 91 > PCB 132 ~ PCB 136 > PCB 95. Atropselective gas chromatography revealed a congener-specific atropisomeric enrichment of major OH-PCB metabolites. Comparison of our results with published OH-PCB patterns and chiral signatures (i.e., the direction and extent of the atropisomeric enrichment) from rat liver microsomal revealed drastic differences between both species, especially following induction of P450 2B enzymes. These species differences in the metabolism of chiral PCBs should be considered in developmental neurotoxicity studies of PCBs. PMID:24107130

  15. CD36-deficient congenic strains show improved glucose tolerance and distinct shifts in metabolic and transcriptomic profiles.

    PubMed

    Šedová, L; Liška, F; Křenová, D; Kazdová, L; Tremblay, J; Krupková, M; Corbeil, G; Hamet, P; Křen, V; Šeda, O

    2012-07-01

    Deficiency of fatty acid translocase Cd36 has been shown to have a major role in the pathogenesis of metabolic syndrome in the spontaneously hypertensive rat (SHR). We have tested the hypothesis that the effects of Cd36 mutation on the features of metabolic syndrome are contextually dependent on genomic background. We have derived two new congenic strains by introgression of limited chromosome 4 regions of SHR origin, both including the defective Cd36 gene, into the genetic background of a highly inbred model of insulin resistance and dyslipidemia, polydactylous (PD) rat strain. We subjected standard diet-fed adult males of PD and the congenic PD.SHR4 strains to metabolic, morphometric and transcriptomic profiling. We observed significantly improved glucose tolerance and lower fasting insulin levels in PD.SHR4 congenics than in PD. One of the PD.SHR4 strains showed lower triglyceride concentrations across major lipoprotein fractions combined with higher levels of low-density lipoprotein cholesterol compared with the PD progenitor. The hepatic transcriptome assessment revealed a network of genes differentially expressed between PD and PD.SHR4 with significant enrichment by members of the circadian rhythmicity pathway (Arntl (Bmal1), Clock, Nfil3, Per2 and Per3). In summary, the introduction of the chromosome 4 region of SHR origin including defective Cd36 into the PD genetic background resulted in disconnected shifts of metabolic profile along with distinct changes in hepatic transcriptome. The synthesis of the current results with those obtained in other Cd36-deficient strains indicates that the eventual metabolic effect of a deleterious mutation such as that of SHR-derived Cd36 is not absolute, but rather a function of complex interactions between environmental and genomic background, upon which it operates.

  16. Oleocanthal Modulates Estradiol-Induced Gene Expression Involving Estrogen Receptor α.

    PubMed

    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. PMID:26166135

  17. Estrogen Receptor Alpha Polymorphisms, Estradiol Level, and Occurrence of Atherosclerosis Risk Factors in Healthy Postmenopausal Women

    PubMed Central

    Bojar, Iwona; Gujski, Mariusz; Raczkiewicz, Dorota; Łyszcz, Robert; Owoc, Jakub; Walecka, Irena

    2015-01-01

    Background The objective of the study was to analyze the relationship between interaction of polymorphisms in the estrogen receptor alpha gene (Erα) and estradiol (E2), and the occurrence of selected atherosclerosis risk factors in postmenopausal women without the diagnosis of a cardiovascular disease. Material/Methods The study covered 210 women, a minimum of 2 years after menopause, with FSH >30 mlU/ml, aged 50–60 years, with no chronic diseases diagnosed. In the women examined, the levels of estradiol, total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides were determined, as well as height, waist circumference (W), hip circumference (R), and arterial hypertension. The BMI and W/H ratio were calculated. Genotyping of the ER-α polymorphism was performed using a polymerase chain reaction and restriction enzymes (PCR-RFLP). The alleles of the XbaI polymorphism were defined as A and G: heterozygote AG, wild type GG and homozygote AA. The alleles of PvuII polymorphism were defined as T and C: heterozygote TC, homozygote TT, and wild type CC. Results The concentration of endogenous estradiol and ERα XbaI and PuvII polymorphisms as independent parameters did not significantly affect the BMI, waist circumference, W/H ratio, levels of CHOL, HDL, LDL, TG, or LDL/HDL, nor the systole and diastole in the postmenopausal women in the study. Conclusions The presented study suggests that ERα XbaI AA polymorphism may intensify the beneficial effect of estradiol on the distribution of fatty tissue after menopause; ERα XbaI GG and PuvII TC genotypes may intensify the beneficial effect of estradiol on HDL level; ERα PuvII TT genotype unfavorably modifies the relation between concentration of estradiol and systolic pressure after menopause. PMID:25836047

  18. Effect of estradiol and bisphenol A on human hepatoblastoma cell viability and telomerase activity

    PubMed Central

    Xu, B.L.; Zhao, Q.Z.; Gao, X.Y.; Hou, G.J.

    2015-01-01

    Sex hormones from environmental and physiological sources might play a major role in the pathogenesis of hepatoblastoma in children. This study investigated the effects of estradiol and bisphenol A on the proliferation and telomerase activity of human hepatoblastoma HepG2 cells. The cells were divided into 6 treatment groups: control, bisphenol A, estradiol, anti-estrogen ICI 182,780 (hereinafter ICI), bisphenol A+ICI, and estradiol+ICI. Cell proliferation was measured based on average absorbance using the Cell Counting-8 assay. The cell cycle distribution and apoptotic index were determined by flow cytometry. Telomerase activity was detected by polymerase chain reaction and a telomeric repeat amplification protocol assay. A higher cell density was observed in bisphenol A (P<0.01) and estradiol (P<0.05) groups compared with the control group. Cell numbers in S and G2/M phases after treatment for 48 h were higher (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h (P<0.05) were higher in these groups than in the control group. The cell density was also higher in bisphenol A+ICI (P<0.01) and estradiol+ICI (P<0.05) groups compared with the ICI group. Furthermore, cell numbers were increased in S and G2/M phases (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h were higher (P<0.05) in these groups than in the ICI group. Therefore, bisphenol A and estradiol promote HepG2 cell proliferation in vitro by inhibition of apoptosis and stimulation of telomerase activity via an estrogen receptor-dependent pathway. PMID:26397976

  19. Estradiol and progesterone strongly inhibit the innate immune response of mononuclear cells in newborns.

    PubMed

    Giannoni, Eric; Guignard, Laurence; Knaup Reymond, Marlies; Perreau, Matthieu; Roth-Kleiner, Matthias; Calandra, Thierry; Roger, Thierry

    2011-07-01

    Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period.

  20. Estradiol modulates medial prefrontal cortex and amygdala activity during fear extinction in women and female rats

    PubMed Central

    Zeidan, Mohamed A.; Igoe, Sarah A.; Linnman, Clas; Vitalo, Antonia; Levine, John B.; Klibanski, Anne; Goldstein, Jill M.; Milad, Mohammed R.

    2011-01-01

    Background Men and women differ in their ability to extinguish fear. Fear extinction requires the activation of brain regions including the ventromedial prefrontal cortex (vmPFC) and amygdala. Could estradiol modulate the activity of these brain regions during fear extinction? Methods All rat experiments were conducted in naturally cycling females. Rats underwent fear conditioning on day 1. On day 2, they underwent extinction training during the metestrus phase of the cycle (low estrogen and progesterone). Extinction recall was assessed on day 3. Systemic injections of estrogen-receptor beta and alpha agonists, and estradiol were administered at different time points to assess their influence on extinction consolidation and c-fos expression in the vmPFC and amygdala. In parallel, healthy naturally cycling women underwent an analogous fear conditioning extinction training while in a 3T fMRI scanner. Measurement of their estradiol levels and skin conductance responses were obtained throughout the experiment. Results In female rats, administration of the estrogen-receptor beta (but not alpha) agonist facilitated extinction recall. Immediate (but not delayed) post-extinction training administration of estradiol facilitated extinction memory consolidation and increased c-fos expression in the vmPFC while reducing it in the amygdala. In parallel, natural variance in estradiol in pre-menopausal cycling women modulated vmPFC and amygdala reactivity and facilitated extinction recall. Conclusion We provide translational evidence that demonstrates the influence of endogenous and exogenous estradiol on the fear extinction network. Our data suggest that women’s endogenous hormonal status should be considered in future neurobiological research related to anxiety and mood disorders. PMID:21762880

  1. Effect of estradiol and bisphenol A on human hepatoblastoma cell viability and telomerase activity.

    PubMed

    Xu, B L; Zhao, Q Z; Gao, X Y; Hou, G J

    2015-11-01

    Sex hormones from environmental and physiological sources might play a major role in the pathogenesis of hepatoblastoma in children. This study investigated the effects of estradiol and bisphenol A on the proliferation and telomerase activity of human hepatoblastoma HepG2 cells. The cells were divided into 6 treatment groups: control, bisphenol A, estradiol, anti-estrogen ICI 182,780 (hereinafter ICI), bisphenol A+ICI, and estradiol+ICI. Cell proliferation was measured based on average absorbance using the Cell Counting-8 assay. The cell cycle distribution and apoptotic index were determined by flow cytometry. Telomerase activity was detected by polymerase chain reaction and a telomeric repeat amplification protocol assay. A higher cell density was observed in bisphenol A (P<0.01) and estradiol (P<0.05) groups compared with the control group. Cell numbers in S and G2/M phases after treatment for 48 h were higher (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h (P<0.05) were higher in these groups than in the control group. The cell density was also higher in bisphenol A+ICI (P<0.01) and estradiol+ICI (P<0.05) groups compared with the ICI group. Furthermore, cell numbers were increased in S and G2/M phases (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h were higher (P<0.05) in these groups than in the ICI group. Therefore, bisphenol A and estradiol promote HepG2 cell proliferation in vitro by inhibition of apoptosis and stimulation of telomerase activity via an estrogen receptor-dependent pathway.

  2. Polymethoxyflavones as agents that prevent formation of cataract: nobiletin congeners show potent growth inhibitory effects in human lens epithelial cells.

    PubMed

    Miyata, Yoshiki; Oshitari, Tetsuta; Okuyama, Yuji; Shimada, Arata; Takahashi, Hideyo; Natsugari, Hideaki; Kosano, Hiroshi

    2013-01-01

    Posterior capsular opacification (PCO) is the most frequent complication and the primary reason for visual decrease after extracapsular cataract surgery. The proliferation and migration of leftover lens epithelial cells (LECs) after surgery may contribute to the development of PCO. To prevent PCO, a rational approach would be to inhibit both the proliferation and the migration of LECs using nontoxic xenobiotics. Nobiletin, one of the most abundant polymethoxyflavones (PMFs) in citrus peel, and its synthetic congeners displayed a potent inhibition of LEC proliferation. Structural features which enhance anti-proliferative activity have also been discussed.

  3. Isolation of a Genomic Region Affecting Most Components of Metabolic Syndrome in a Chromosome-16 Congenic Rat Model

    PubMed Central

    Šedová, Lucie; Pravenec, Michal; Křenová, Drahomíra; Kazdová, Ludmila; Zídek, Václav; Krupková, Michaela; Liška, František; Křen, Vladimír; Šeda, Ondřej

    2016-01-01

    Metabolic syndrome is a highly prevalent human disease with substantial genomic and environmental components. Previous studies indicate the presence of significant genetic determinants of several features of metabolic syndrome on rat chromosome 16 (RNO16) and the syntenic regions of human genome. We derived the SHR.BN16 congenic strain by introgression of a limited RNO16 region from the Brown Norway congenic strain (BN-Lx) into the genomic background of the spontaneously hypertensive rat (SHR) strain. We compared the morphometric, metabolic, and hemodynamic profiles of adult male SHR and SHR.BN16 rats. We also compared in silico the DNA sequences for the differential segment in the BN-Lx and SHR parental strains. SHR.BN16 congenic rats had significantly lower weight, decreased concentrations of total triglycerides and cholesterol, and improved glucose tolerance compared with SHR rats. The concentrations of insulin, free fatty acids, and adiponectin were comparable between the two strains. SHR.BN16 rats had significantly lower systolic (18–28 mmHg difference) and diastolic (10–15 mmHg difference) blood pressure throughout the experiment (repeated-measures ANOVA, P < 0.001). The differential segment spans approximately 22 Mb of the telomeric part of the short arm of RNO16. The in silico analyses revealed over 1200 DNA variants between the BN-Lx and SHR genomes in the SHR.BN16 differential segment, 44 of which lead to missense mutations, and only eight of which (in Asb14, Il17rd, Itih1, Syt15, Ercc6, RGD1564958, Tmem161a, and Gatad2a genes) are predicted to be damaging to the protein product. Furthermore, a number of genes within the RNO16 differential segment associated with metabolic syndrome components in human studies showed polymorphisms between SHR and BN-Lx (including Lpl, Nrg3, Pbx4, Cilp2, and Stab1). Our novel congenic rat model demonstrates that a limited genomic region on RNO16 in the SHR significantly affects many of the features of metabolic syndrome

  4. Isolation of a Genomic Region Affecting Most Components of Metabolic Syndrome in a Chromosome-16 Congenic Rat Model.

    PubMed

    Šedová, Lucie; Pravenec, Michal; Křenová, Drahomíra; Kazdová, Ludmila; Zídek, Václav; Krupková, Michaela; Liška, František; Křen, Vladimír; Šeda, Ondřej

    2016-01-01

    Metabolic syndrome is a highly prevalent human disease with substantial genomic and environmental components. Previous studies indicate the presence of significant genetic determinants of several features of metabolic syndrome on rat chromosome 16 (RNO16) and the syntenic regions of human genome. We derived the SHR.BN16 congenic strain by introgression of a limited RNO16 region from the Brown Norway congenic strain (BN-Lx) into the genomic background of the spontaneously hypertensive rat (SHR) strain. We compared the morphometric, metabolic, and hemodynamic profiles of adult male SHR and SHR.BN16 rats. We also compared in silico the DNA sequences for the differential segment in the BN-Lx and SHR parental strains. SHR.BN16 congenic rats had significantly lower weight, decreased concentrations of total triglycerides and cholesterol, and improved glucose tolerance compared with SHR rats. The concentrations of insulin, free fatty acids, and adiponectin were comparable between the two strains. SHR.BN16 rats had significantly lower systolic (18-28 mmHg difference) and diastolic (10-15 mmHg difference) blood pressure throughout the experiment (repeated-measures ANOVA, P < 0.001). The differential segment spans approximately 22 Mb of the telomeric part of the short arm of RNO16. The in silico analyses revealed over 1200 DNA variants between the BN-Lx and SHR genomes in the SHR.BN16 differential segment, 44 of which lead to missense mutations, and only eight of which (in Asb14, Il17rd, Itih1, Syt15, Ercc6, RGD1564958, Tmem161a, and Gatad2a genes) are predicted to be damaging to the protein product. Furthermore, a number of genes within the RNO16 differential segment associated with metabolic syndrome components in human studies showed polymorphisms between SHR and BN-Lx (including Lpl, Nrg3, Pbx4, Cilp2, and Stab1). Our novel congenic rat model demonstrates that a limited genomic region on RNO16 in the SHR significantly affects many of the features of metabolic syndrome.

  5. Differential accumulation of polychlorinated biphenyl congeners in the terrestrial food web of the Kalamazoo River Superfund site, Michigan.

    PubMed

    Blankenship, Alan L; Zwiernik, Matthew J; Coady, Katherine K; Kay, Denise P; Newsted, John L; Strause, Karl; Park, Cyrus; Bradley, Patrick W; Neigh, Arianne M; Millsap, Stephanie D; Jones, Paul D; Giesy, John P

    2005-08-15

    A series of field studies was conducted to determine the bioaccumulation of polychlorinated biphenyl (PCB) congeners in the terrestrial food web of the Kalamazoo River flood plain. Samples included colocated soils, native plants likely to be consumed by wildlife, several taxa of terrestrial invertebrates, small mammals, passerine bird eggs, nestlings, and adults, and great horned owl plasma and eggs. Mean concentrations of total PCBs in samples from the former Trowbridge impoundment were 6.5 mg/kg dry weight for soils and 0.023, 0.13, 1.3, 1.3, 1.6, and 8.2 mg/kg wet weight for plants, small herbivorous mammals, depurated earthworms, shrews, great horned owl eggs, and house wren eggs, respectively. Historical data from the Kalamazoo River have reported Aroclor-equivalent total PCB concentrations in the terrestrial food web; however, the degree of environmental weathering of the parent PCB mixtures was unknown. In this study, earthworms and composite samples of coleoptera exhibited PCB congener patterns that were similar to patterns in colocated soils. However, in plants, less chlorinated PCBs (e.g., mono-, di-, tri-, and tetrachlorinated biphenyls) were predominant, and in small mammals, there was a notable enrichment of PCBs 153, 180, 138, 118, and 99. In general, concentrations of PCBs were lower in most biota than in soil from the Kalamazoo River Area of Concern (KRAOC) although there was a modest biomagnification of PCBs from lower trophic level biota to highertrophic levels. As a consequence of environmental weathering of PCBs in the terrestrial food web of the KRAOC, the relative potency of the PCBs (expressed as mg TEQs/kg PCBs) decreased from soil to most biota. While there was a general trend, as expected, in which concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) increased with total PCBs, this relationship was rather poor (R2 = 0.13). Taken together, these data suggest that the differential accumulation of PCB congeners in the

  6. Effects of Estradiol and Venlafaxine on Insomnia Symptoms and Sleep Quality in Women with Hot Flashes

    PubMed Central

    Ensrud, Kristine E.; Guthrie, Katherine A.; Hohensee, Chancellor; Caan, Bette; Carpenter, Janet S.; Freeman, Ellen W.; LaCroix, Andrea Z.; Landis, Carol A.; Manson, JoAnn; Newton, Katherine M.; Otte, Julie; Reed, Susan D.; Shifren, Jan L.; Sternfeld, Barbara; Woods, Nancy F.; Joffe, Hadine

    2015-01-01

    Study Objectives: Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes. Design: 3-arm double-blind randomized trial. Participants assigned in a 2:2:3 ratio to 17β estradiol 0.5 mg/day (n = 97), venlafaxine XR 75 mg/day (n = 96), or placebo (n = 146) for 8 weeks. Setting: Academic research centers. Participants: 339 community-dwelling perimenopausal and postmenopausal women with ≥ 2 bothersome hot flashes per day. Measurements and Results: Insomnia symptoms (Insomnia Severity Index [ISI]) and sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at baseline, week 4 and 8; 325 women (96%) provided ISI data and 312 women (92%) provided PSQI data at baseline and follow-up. At baseline, mean (SD) hot flash frequency was 8.1/day (5.3), mean ISI was 11.1 (6.0), and mean PSQI was 7.5 (3.4). Mean (95% CI) change from baseline in ISI at week 8 was −4.1 points (−5.3 to −3.0) with estradiol, −5.0 points (−6.1 to −3.9) with venlafaxine, and −3.0 points (−3.8 to −2.3) with placebo (P overall treatment effect vs. placebo 0.09 for estradiol and 0.007 for venlafaxine). Mean (95% CI) change from baseline in PSQI at week 8 was −2.2 points (−2.8 to −1.6) with estradiol, −2.3 points (−2.9 to −1.6) with venlafaxine, and −1.2 points (−1.7 to −0.8) with placebo (P overall treatment effect vs. placebo 0.04 for estradiol and 0.06 for venlafaxine). Conclusions: Among perimenopausal and postmenopausal women with hot flashes, both low dose oral estradiol and low-dose venlafaxine compared with placebo modestly reduced insomnia symptoms and improved subjective sleep quality. Clinical Trial Registration: NCT01418209 at www.clinicaltrials.gov Citation: Ensrud KE, Guthrie KA, Hohensee C, Caan B, Carpenter JS, Freeman EW, LaCroix AZ, Landis CA, Manson J, Newton KM, Otte J, Reed SD, Shifren JL, Sternfeld B, Woods NF, Joffe H. Effects of estradiol and venlafaxine on insomnia symptoms

  7. Congener profiles of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in sediment, water, and fish at a soil contamination site in Taiwan.

    PubMed

    Chang, Hwang-Jen; Lin, Tsair-Fuh; Whang, Liang-Ming; Wu, Yi-Ju

    2016-01-01

    The relationship of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in sediment, water, and fish was studied for 55 fish farms near a contaminated site in Tainan, Taiwan. Samples were collected from the farms and analyzed for seventeen 2,3,7,8-substituted PCDD/Fs congeners. High correlations were found between PCDD/Fs in water and sediment in regard to both concentration and toxicity (R(2) = 0.933 for concentration and R(2) = 0.832 for toxicity). The congener profiles of the 17 PCDD/Fs in water were similar to those in the sediment. However, the PCDD/Fs congener composition in the fish and fish belly samples were different from those in the sediment and water samples obtained from the same fish farm and were also different among the fish samples. It is thus suggested that the biotic PCDD/Fs distribution is more complex than the abiotic PCDD/Fs distribution. Among the seven factors analyzed, only the lipid percentage presented a relationship with the PCDD/Fs congener composition in the fish and fish bellies. A multiple linear regression of the concentration of each congener in the fish was conducted using the concentration of each congener in the site-matched sediment and the lipid content of the fish as independent variables. The results showed that only seven PCDD/Fs congeners with a lower degree of chlorination, which were 4-6 chlorine substitutes, in the fish presented a significant correlation with the lipid content in the fish and their concentration in sediment (r > 0.65, P < 0.005 for both independent variables). In addition, the octanol-water partition coefficients were not significantly related to this distribution behavior.

  8. Comparison of Gas Chromatography and Mineralization Experiments for Measuring Loss of Selected Polychlorinated Biphenyl Congeners in Cultures of White Rot Fungi

    PubMed Central

    Beaudette, Lee A.; Davies, Stephen; Fedorak, Phillip M.; Ward, Owen P.; Pickard, Michael A.

    1998-01-01

    Two methods were used to compare the biodegradation of six polychlorinated biphenyl (PCB) congeners by 12 white rot fungi. Four fungi were found to be more active than Phanerochaete chrysosporium ATCC 24725. Biodegradation of the following congeners was monitored by gas chromatography: 2,3-dichlorobiphenyl, 4,4′-dichlorobiphenyl, 2,4′,5-trichlorobiphenyl (2,4′,5-TCB), 2,2′,4,4′-tetrachlorobiphenyl, 2,2′,5,5′-tetrachlorobiphenyl, and 2,2′,4,4′,5,5′-hexachlorobiphenyl. The congener tested for mineralization was 2,4′,5-[U-14C]TCB. Culture supernatants were also assayed for lignin peroxidase and manganese peroxidase activities. Of the fungi tested, two strains of Bjerkandera adusta (UAMH 8258 and UAMH 7308), one strain of Pleurotus ostreatus (UAMH 7964), and Trametes versicolor UAMH 8272 gave the highest biodegradation and mineralization. P. chrysosporium ATCC 24725, a strain frequently used in studies of PCB degradation, gave the lowest mineralization and biodegradation activities of the 12 fungi reported here. Low but detectable levels of lignin peroxidase and manganese peroxidase activity were present in culture supernatants, but no correlation was observed among any combination of PCB congener biodegradation, mineralization, and lignin peroxidase or manganese peroxidase activity. With the exception of P. chrysosporium, congener loss ranged from 40 to 96%; however, these values varied due to nonspecific congener binding to fungal biomass and glassware. Mineralization was much lower, ≤11%, because it measures a complete oxidation of at least part of the congener molecule but the results were more consistent and therefore more reliable in assessment of PCB biodegradation. PMID:9603809

  9. Separation of dansylated 17β-estradiol, 17α-estradiol, and estrone on a single HPLC column for simultaneous quantitation by LC-MS/MS.

    PubMed

    Szarka, Szabolcs; Nguyen, Vien; Prokai, Laszlo; Prokai-Tatrai, Katalin

    2013-04-01

    We show here that baseline separation of dansylated estrone, 17β-estradiol, and 17α-estradiol can be done, contrary to previous reports, within a short run time on a single RP-LC analytical column packed with particles bonded with phenyl-hexyl stationary phase. The chromatographic method coupled with isotope dilution tandem MS offers a simple assay enabling the simultaneous analysis of these analytes. The method employs (13)C-labeled estrogens as internal standards to eliminate potential matrix effects arising from the use of deuterated estrogens. The assay also offers adequate accuracy and sensitivity to be useful for biological samples. The practical applicability of the validated method is demonstrated by the quantitative analyses of in vivo samples obtained from rats treated with Premarin®. PMID:23371528

  10. Separation of dansylated 17β-estradiol, 17α-estradiol and estrone on a single HPLC column for simultaneous quantitation by LC-MS/MS

    PubMed Central

    Szarka, Szabolcs; Nguyen, Vien; Prokai, Laszlo; Prokai-Tatrai, Katalin

    2013-01-01

    We show here that baseline separation of dansylated estrone, 17β-estradiol and 17α-estradiol can be done, contrary to previous reports, within a short run time on a single RP-LC analytical column packed with particles bonded with phenyl-hexyl stationary phase. The chromatographic method coupled with isotope-dilution tandem MS offers a simple assay enabling the simultaneous analysis of these analytes. The method employs 13C-labeled estrogens as internal standards to eliminate potential matrix effects arising from the use of deuterated estrogens. The assay also offers adequate accuracy and sensitivity to be useful for biological samples. The practical applicability of the validated method is demonstrated by the quantitative analyses of in vivo samples obtained from rats treated with Premarin®. PMID:23371528

  11. Developmental programming: contribution of prenatal androgen and estrogen to estradiol feedback systems and periovulatory hormonal dynamics in sheep.

    PubMed

    Veiga-Lopez, Almudena; Astapova, Olga I; Aizenberg, Esther F; Lee, James S; Padmanabhan, Vasantha

    2009-04-01

    Prenatal testosterone excess leads to neuroendocrine and periovulatory disruptions in the offspring culminating in progressive loss of cyclicity. It is unknown whether the mediary of these disruptions is androgen or estrogen, because testosterone can be aromatized to estrogen. Taking a reproductive life span approach of studying control, prenatal testosterone, and dihydrotestosterone-treated offspring, this study tested the hypothesis that disruptions in estradiol-negative but not -positive feedback effects are programmed by androgenic actions of testosterone and that these disruptions in turn will have an impact on the periovulatory hormonal dynamics. The approach was to test estradiol-negative and -positive feedback responses of all three groups of ovary-intact females during prepubertal age and then compare the periovulatory dynamics of luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone during the first breeding season. The findings show that estradiol-negative but not estradiol-positive feedback disruptions in prenatal testosterone-treated females are programmed by androgenic actions of prenatal testosterone excess and that follicular phase estradiol and gonadotropins surge disruptions during reproductive life are consistent with estrogenic programming. Additional studies carried out testing estradiol-positive feedback response over time found progressive deterioration of estradiol-positive feedback in prenatal testosterone-treated sheep until the time of puberty. Together, these findings provide insight into the mechanisms by which prenatal testosterone disrupts the reproductive axis. The findings may be of translational relevance since daughters of mothers with hyperandrogenism are at risk of increased exposure to androgens.

  12. Association of circulating concentrations of estradiol during the preovulatory period and expression of steroidogenic enzymes in beef cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cows with greater circulating concentrations of estradiol during the preovulatory period (HighE2) have increased pregnancy success following a fixed-time AI protocol. Furthermore, these animals have an enhanced ability to produce estradiol as indicated by increased expression of CYP19A1 and LHR wit...

  13. Changes in ovarian function associated with circulating concentrations of estradiol before a GnRH-induced ovulation in beef cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    These studies were conducted to evaluate causes for differences in circulating concentrations of estradiol prior to a GnRH-induced ovulation and to determine if exogenous GnRH administration could alter LH secretion and subsequent follicular estradiol production. Beef cows (Experiment 1; n = 32, Ex...

  14. Estradiol acts via estrogen receptors alpha and beta on pathways important for synaptic plasticity in the mouse hippocampal formation

    PubMed Central

    Spencer-Segal, Joanna L.; Tsuda, Mumeko C.; Mattei, Larissa; Waters, Elizabeth M.; Romeo, Russell D.; Milner, Teresa A.; McEwen, Bruce S.; Ogawa, Sonoko

    2012-01-01

    Estradiol affects hippocampal-dependent spatial memory and underlying structural and electrical synaptic plasticity in female mice and rats. Using estrogen receptor (ER) alpha and beta knockout mice and wild-type littermates, we investigated the role of ERs in estradiol effects on multiple pathways important for hippocampal plasticity and learning. Six hours of estradiol administration increased immunoreactivity for phosphorylated Akt throughout the hippocampal formation, while 48 hours of estradiol increased immunoreactivity for phosphorylated TrkB receptor. Estradiol effects on phosphorylated Akt and TrkB immunoreactivities were abolished in ER alpha and ER beta knockout mice. Estradiol also had distinct effects on immunoreactivity for PSD-95 and BDNF mRNA in ER alpha and beta knockout mice. Thus, estradiol acts through both ERs alpha and beta in several subregions of the hippocampal formation. The different effects of estradiol at 6 and 48 hours indicate that several mechanisms of estrogen receptor signaling contribute to this female hormone’s influence on hippocampal synaptic plasticity. By further delineating these mechanisms, we will better understand and predict the effects of endogenous and exogenous ovarian steroids on mood, cognition, and other hippocampal-dependent behaviors. PMID:22133892

  15. Interaction of estradiol, testosterone, and progesterone in the modulation of hormone-dependent aggression in the female rat.

    PubMed

    Albert, D J; Jonik, R H; Walsh, M L

    1992-10-01

    Female rats that had become aggressive as a result of cohabiting with a sterile male were ovariectomized and implanted with Silastic tubes of estradiol, testosterone, and progesterone, estradiol and testosterone alone, or with empty tubes. The implants were designed to model serum concentrations present during the last week of pregnancy (estradiol, 0.06 ng/ml; testosterone, 2.6 ng/ml; progesterone, 70 ng/ml). Following a test of aggression 1 week postoperatively, estradiol and testosterone implants were replaced with ones designed to maintain the lower hormone levels present following parturition (0.02 ng/ml; 0.6 ng/ml, respectively). Progesterone was not replaced. At the first aggression test, females with estradiol and testosterone alone displayed significantly more aggression than females with these hormones plus progesterone. Both groups were more aggressive than females without hormone replacement. Following the exchange of large implants for small ones, females that previously had progesterone increased in aggression while females that previously had only estradiol and testosterone decreased in aggression. Both groups continued to be more aggressive than the group without hormone replacement. High serum progesterone present near the end of pregnancy appears to moderate the expression of aggression supported by estradiol and testosterone. Conversely, progesterone's decline at parturition appears to produce a rebound facilitation of aggression even though serum estradiol and testosterone simultaneously decline.

  16. 76 FR 75886 - Determination That DEMULEN 1/50-28 (Ethinyl Estradiol; Ethynodiol Diacetate) Tablet and Four...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ...-28 (ethinyl Wyeth estradiol; Pharmaceuticals levonorgestrel) , Inc., P.O. Tablet, 0.03 mg, 0.04 Box... (ethinyl Do. estradiol; levonorgestrel) Tablet, 0.03 mg, 0.04 mg, 0.03 mg; 0.05 mg, 0.075 mg, 0.125 mg....

  17. Stimulation of RNA polymerase I and II activities by 17 beta -estradiol receptor on chick liver chromatin.

    PubMed Central

    Dierks-Ventling, C; Bieri-Bonniot, F

    1977-01-01

    The endogenous transcriptional capacity (RNA polymerase I and II activity) of liver chromatin from chicks treated with 17 beta-estradiol for 24 h (E 24) was double that of the controls. E 24 chromatin contained estradiol receptor activity while control chromatin did not. Its presence suggested an implication in the enhanced activities of RNA polymerases of E 24 chromatin. When semi-purified estradiol receptor was added to control chromatin, the endogenous transcriptional capacity of this chromatin was greatly increased. Studies with alpha-amanitin showed that both RNA polymerase I and II were stimulated by the estradiol receptor. This stimulation was observed as long as homology of the system was maintained. Solubilized homologous RNA polymerases were stimulated much less by the hormone complex in the presence of heterologous DNA than with homologous chromatin. Prokaryotic RNA polymerase could not be stimulated by chick liver estradiol receptor in the presence of heterologous DNA. PMID:840645

  18. Cyclic estradiol treatment normalizes body weight and restores physiological patterns of spontaneous feeding and sexual receptivity in ovariectomized rats.

    PubMed

    Asarian, Lori; Geary, Nori

    2002-12-01

    Hypothalamic-pituitary-gonadal axis function strongly influences feeding and body weight in cycling females in many species. To test the sufficiency of cyclic variations in plasma estradiol to reproduce normal patterns of spontaneous feeding, food intake, and body weight, ovariectomized Long-Evans rats were subcutaneously injected every fourth day with 2 microg estradiol benzoate or with the oil vehicle alone. Cyclic estradiol treatment completely normalized the trajectory of body weight gain and total food intake through seven treatment cycles. The hyperphagia of ovariectomized rats was expressed as an increase in spontaneous meal size. Meal frequency decreased, but not enough to compensate for the increase in meal size. Estradiol treatment normalized both parameters. In addition, cyclic estradiol treatment produced a further phasic decrease in meal size (and increase in meal frequency) and a decrease in food intake during the second night after injection. This phasic change is similar to the feeding changes occurring during estrus in intact rats. Sexual receptivity was measured during the eighth estradiol treatment cycle, 4 h after injection of 0.5 mg progesterone. Lordosis scores at the time of the treatment cycle modeling estrus were maximal, and scores at the time modeling diestrus were slightly increased over those of rats that did not receive estradiol. Finally, plasma estradiol levels, measured during the ninth treatment cycle, revealed a near-normal cyclic pattern of plasma estradiol levels. These results provide the first demonstration that the induction of a cyclic, near-physiological pattern of plasma estradiol is sufficient to maintain normal levels of body weight, spontaneous feeding patterns, total food intake, and (together with progesterone) sexual receptivity in ovariectomized rats.

  19. Striatal transcriptome analysis of a congenic mouse line (chromosome 11: 50-60Mb) exhibiting reduced methamphetamine sensitivity.

    PubMed

    Yazdani, Neema; Shen, Ying; Johnson, W Evan; Bryant, Camron D

    2016-06-01

    Addiction to psychostimulants such as Methamphetamine (MA) is a significant public health issue in the United States and currently, there are no FDA approved pharmacological interventions. Previously, using short term-selected mouse lines for high and low MA sensitivity that were derived from an F2 cross between C57BL/6J (B6) and DBA/2J (D2) strains, we identified a quantitative trait locus (QTL) on chromosome (chr) 11 that influenced sensitivity to MA-induced locomotor activity (D2 < B6). Using interval-specific murine congenic lines containing various D2 allelic segments on a B6 background, we fine mapped the QTL to a 206 kb critical interval on chromosome 11. To investigate the neurobiological mechanism by which this QTL decreases MA sensitivity, we conducted transcriptome analysis in a 10 Mb congenic mouse (chromosome 11: 50-60 Mb) on whole-striatum brain tissue punches compared to wild-type B6 littermate controls [1]. The data from this study can be found in the NCBI Gene Expression Omnibus (GSE66366). PMID:27222804

  20. Seasonal variation of polychlorinated biphenyl congeners in surficial sediment, trapped settling material, and suspended particulate material in Lake Michigan, USA.

    PubMed

    Robinson, Sander D; Landrum, Peter F; Van Hoof, Patricia L; Eadie, Brian J

    2008-02-01

    A unique time series of surface sediment, trapped settling material, and suspended particulate material polychlorinated biphenyl (PCB) samples were collected at a 45-m deep site off Grand Haven (MI, USA) over a 14-month period. Both concentrations and congener distributions remained constant for the sediments, although there were seasonal and interannual variability in the other matrices. Trapped settling material and suspended particulate material PCB concentrations were substantially lower (~50%) in 1997 than in the samples from December 1997 through July 1998. The cause could not be determined from the data collected, but there were some very large storms during the winter-spring period of 1998, resulting in major sediment resuspension throughout the southern basin. Observed seasonal variation in PCB concentration and congener distribution on particles likely was due to the changes in particle composition. These include particle size and the source of particles (such as the amount of resuspended sediment in trapped settling material), and the role of diagenesis of the organic matter on particles.

  1. Investigations on the sorption of a toxaphene model congener, the B7-1450, on marine sediments.

    PubMed

    Soubaneh, Youssouf Djibril; Lebeuf, Michel; Gouteux, Bruno; Xie, Huixiang; Nikiforov, Vladimir; Gagné, Jean-Pierre

    2008-04-01

    Sorption is a natural process that takes place in sediments or soils and changes the mobility and availability of hydrophobic organic compounds, such as toxaphene pesticide in the environment. The sorption of the 2-exo,3-endo,5-exo,8,9,10,10-heptachlorobornane (B7-1450), used as a model compound of the toxaphene heptachlorobornane congeners found in sediments, was investigated for the first time through a series of batch sorption experiments. The losses of B7-1450 due to adsorption onto glass walls and to evaporation occurring during analytical treatment steps were corrected. The study showed that these specific losses ranged from 2% to 3.5% for the glass walls adsorption and can be as high as 15% for the evaporation treatment. The sorption coefficients, K(d) and K(oc), of B7-1450 could be overestimated by >30%, particularly for low-concentration samples, if the losses were not corrected. Loss correction equations were established, validated and applied to determine sorption coefficients for the B7-1450 congener. The K(oc) values for B7-1450 determined over a gradient of concentrations ranged from 3.5x10(4) to 6.5x10(4)mlg(-1), revealing a strong affinity of B7-1450 for marine sediments. PMID:18295821

  2. Polychlorinated biphenyls (PCBs) in industrial and municipal effluents: concentrations, congener profiles, and partitioning onto particulates and organic carbon.

    PubMed

    Balasubramani, Aparna; Howell, Nathan L; Rifai, Hanadi S

    2014-03-01

    Wastewater effluent samples were collected in the summer of 2009 from 16 different locations which included municipal and industrial wastewater treatment plants and petrochemical industrial outfalls in the Houston area. The effluent samples were analyzed for all 209 polychlorinated biphenyls (PCBs) congeners using high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS) using the USEPA method 1668A. The total PCBs (∑209) concentration in the dissolved medium ranged from 1.01 to 8.12 ng/L and ranged from 2.03 to 31.2 ng/L in the suspended medium. Lighter PCB congeners exhibited highest concentrations in the dissolved phase whereas, in the suspended phase, heavier PCBs exhibited the highest concentrations. The PCB homolog concentrations were dominated by monochlorobiphenyls through hexachlorobiphenyls, with dichlorobiphenyls exhibiting the highest concentration amongst them at most of the effluent outfalls, in the suspended phase. Both total suspended solids (TSS) and various organic carbon fractions played an important role in the distribution of the suspended fractions of PCBs in the effluents. The log Koc values determined in the effluents suggest that effluent PCB loads might have more risk and impact than what standard partitioning models predict.

  3. Ratio of cord to maternal serum PCB concentrations in relation to their congener-specific physicochemical properties

    PubMed Central

    Lancz, Kinga; Palkovičová, L’ubica; Patayová, Henrieta; Drobná, Beata; Wimmerová, Soňa; Šovčíková, Eva; Kováč, Ján; Farkašová, Dana; Hertz-Picciotto, Irva; Jusko, Todd A.; Trnovec, Tomáš

    2014-01-01

    The aim was to characterize placental transfer of some congeners of polychlorinated biphenyls (PCBs) and to relate human in utero exposure to these pollutants to their physicochemical properties. We included into the study 1134 births during the period 2002–2003 from two highly PCB contaminated districts in eastern Slovakia. Concentrations of 15 PCB congeners (IUPAC No. 28, 52, 101, 123+149, 118, 114, 153, 105, 138+163, 167, 156+171, 157, 180, 170, and 189) in umbilical cord (C) and maternal serum (M) were determined. The C/M ratios were significantly related, either positively or inversely depending on parameter, to the logarithm of partition coefficient octanol-water (KOW), to fusion enthalpy at the melting point, molecular weight, water solubility, total surface area of the molecule, solvent accessible surface area, melting point, molar volume, and molecular electronegativity distance vector. We found an inverse association between log KOW and lipid adjusted log C/M (const= 1.078, b1 = −0.179, p < 0.001, R2 = 0.039). Parameters evaluated were interrelated except fusion enthalpy at the melting point and electron affinity vs. solubility. We discuss the possible role of cholesterol as a transplacental transporter of PCBs. PMID:25277764

  4. Removal efficiencies for 136 tetra- through octa-chlorinated dibenzo-p-dioxins and dibenzofuran congeners with activated carbons.

    PubMed

    Zhou, Xu-Jian; Li, Xiao-Dong; Ni, Ming-Jiang; Cen, Ke-Fa

    2015-11-01

    In this study, the removal efficiency of 136 tetra- to octa-chlorinated dibenzo-p-dioxin (CDD)/furan (F) congeners from a nitrogen + oxygen carrier gas was studied using a laboratory-scale, fixed bed adsorption system. Two kinds of activated carbon with dissimilar pore structures were used as adsorbents. The total concentration of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) in the source gas was 541 ng/Nm(3) and that of the 17 toxic 2,3,7,8-substituted PCDD/Fs 96.35 ng/Nm(3), accounting for 17.8% of the total original weight amount. Their toxic equivalent quantity (TEQ) was 8.31 ng I-TEQ/Nm(3). For both activated carbons, the removal efficiencies of the ten PCDD/F homologue groups rise with chlorine substitution number. The removal efficiencies vary approximately as a power function of vapor pressure (correlation coefficients r(2) = 0.93 and 0.81, respectively). Competitive adsorption and desorption occur as adsorption time went on, causing elution of the lower chlorinated homologues, i.e. tetra-CDD/F and Penta-CDD/F congeners. In addition, there are significantly different concentration distributions for isomers in the same homologue groups. However, their removal efficiencies have weak correlation with their initial concentrations. The correlation coefficients are from -0.47 to 0.32 and from -0.57 to 0.46 respectively for the two kinds of activated carbons.

  5. Efficacy of Marek's disease vaccines in Mhc heterozygous chickens: Mhc congenic x inbred line F1 matings.

    PubMed

    Bacon, L D; Witter, R L

    1995-01-01

    The goal of this study is to demonstrate that Mhc (B) heterozygous chickens differ in efficacy of response to several Marek's disease (MD) vaccines. Four types of B2 heterozygotes, in addition to B2B2 homozygotes, were developed by crossing 15.B congenic males to inbred line 7(1) (B2B2) hens. The five types of F1 chicks were intermingled in isolators and vaccinated with one of four types of MD vaccine before inoculation with the very virulent Md5 strain of MD herpesvirus. The F1 chickens differ in development of protective immunity following MD vaccination from two perspectives. First, chickens of a particular Mhc genotype were protected better by some vaccines than others. Second, individual vaccine preparations protected some Mhc genotypes more effectively. We conclude that some MD vaccines are more appropriate than others for certain B-haplotypes when chickens are heterozygous for the Mhc. The value of using Mhc-congenic x inbred line F1 animals for studies concerning the influence of the Mhc on vaccinal immunity is discussed.

  6. A 25-Year Experience of Gastroenteropancreatic Neuroendocrine Tumors and Somatostatin (Congeners) Analogs: From Symptom Control to Antineoplastic Therapy.

    PubMed

    O'Dorisio, Thomas M; Anthony, Lowell B

    2015-01-01

    Radioimmunoassay technology was utilized in the discovery of somatostatin and was quickly brought into therapeutics; however, it took the development of somatostatin congeners to solve its limitations of a short half-life. Therapeutic medical control of hyperhormonal states such as acromegaly, carcinoid syndrome and VIPoma significantly advanced from a nonspecific approach to one that specifically and effectively targeted the underlying pathophysiology. Clinical care was transformed from nonspecific symptom control to one of a significant improvement in not only quality of life, but also quantity of life. These data submitted to US and European regulatory authorities for approval included many investigative sites with no uniform protocol and multiple investigational new drugs, and have not been previously published. This review includes the original data demonstrating the transformational impact this class of agents had on specific disease subsets resulting in regulatory approval 25 years ago. Autoradiography techniques using somatostatin resulted in identifying, localizing and characterizing its receptor subtypes. Translating in vitro data to in vivo resulted in scintigraphic whole body and SPECT scans with (111)In-pentetreotide and was incorporated into standard clinical care 20 years ago. (68)Ga-octreotide congeners using PET scanning offers a major imaging advance. Peptide receptor radiotherapy has evolved over the last 2 decades and utilizes several therapeutic isotopes, including (90)Y and (177)Lu. PMID:26303712

  7. Fractionation and current time trends of PCB congeners: evolvement of distributions 1950-2010 studied using a global atmosphere-ocean general circulation model

    NASA Astrophysics Data System (ADS)

    Lammel, G.; Stemmler, I.

    2012-08-01

    PCBs are ubiquitous environmental pollutants expected to decline in abiotic environmental media in response to decreasing primary emissions since the 1970s. A coupled atmosphere-ocean general circulation model with embedded dynamic sub-models for atmospheric aerosols and the marine biogeochemistry and air-surface exchange processes with soils, vegetation and the cryosphere is used to study the transport and fate of four PCB congeners covering a range of 3-7 chlorine atoms. The change of the geographic distribution of the PCB mixture reflects the sources and sinks' evolvement over time. Globally, secondary emissions (re-volatilisation from surfaces) are on the long term increasingly gaining importance over primary emissions. Secondary emissions are most important for the congeners with 5-6 chlorine atoms. Correspondingly, the levels of these congeners are predicted to decrease slowest. Changes in congener mixture composition (fractionation) are characterized both geographically and temporally. In high latitudes enrichment of the lighter, less persistent congeners and more delayed decreasing levels in response to decreasing emissions are found. The delivery of the contaminants to high latitudes is predicted to be more efficient than previously suggested. The results suggest furthermore that the effectiveness of emission control measures may significantly vary among substances. The trends of decline of organic contaminant levels in the abiotic environmental media do not only vary with latitude (slow in high latitudes), but do also show longitudinal gradients.

  8. Transcriptional profiling of Chromosome 17 QTL for carbohydrate and total calorie intake in a mouse congenic strain reveals candidate genes and pathways

    PubMed Central

    Kumar, K. Ganesh; Richards, Brenda K. Smith

    2009-01-01

    BACKGROUND/AIMS The genetic basis for ingestive behaviors is virtually unknown. Quantitative trait loci (QTLs) for carbohydrate and energy intake map to mouse chromosome 17 and were previously confirmed by a congenic strain bearing CAST/Ei (CAST) donor segment on the C57BL/6J (B6) background. METHODS We used microarray technology to facilitate gene identification. Gene expression was compared between the B6.CAST-17 (BC-17) congenic and B6 strains in two diets: 1) chow, and 2) carbohydrate/protein vs. fat/protein. RESULTS Within the QTL and unique to macronutrient selection, Agpat1 (acylglycerol-3-phosphate O-acyltransferase 1) was differentially expressed in hypothalamus. Irrespective of diet, the gene with the highest fold difference in congenic mice was trefoil factor 3 (Tff3) in liver. Several genes involved in fat metabolism were decreased in carbohydrate-preferring congenic mice, while genes associated with carbohydrate metabolism were increased. In particular, the glyoxalase pathway was enhanced including Glo1, Glo2, and dLDH. Higher expression of Glo1 mRNA in BC-17 congenic mice corresponded to increased protein expression revealed by Western blot, and to higher GLO1 activity in blood. CONCLUSION These genes represent new candidates for nutrient intake phenotypes. We propose that increased GLO1 in the BC-17 strain supports its need to protect against dietary oxidants resulting from high carbohydrate intake. PMID:19776624

  9. An On-Farm Survey of Spatial and Temporal Stratifications of 17ß-Estradiol Concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol (E2), a natural estrogenic hormone, may cause endocrine disruption in sensitive organisms. It has been reported to dissipate rapidly in soil laboratory studies, but is frequently detected in the environment leading to question about possible sources and processes that explain the mobil...

  10. Microbiological hydroxylation of estradiol: formation of 2- and 4-hydroxyestradiol by Aspergillus alliaceus.

    PubMed Central

    Williamson, J; Van Orden, D; Rosazza, J P

    1985-01-01

    Microorganisms known to hydroxylate alkaloids, amino acids, and aromatic substrates were examined for their potential to hydroxylate 17 beta-estradiol and estrone. Thin-layer chromatography of fermentation extracts revealed a wide range of steroid products. Aspergillus alliaceus (UI 315) was the only culture capable of producing good yields of catechol estrogens with 17 beta-estradiol. The organism also transformed estrone but not to catechol products. Analytical experiments with high-performance liquid chromatography revealed that A. alliaceus formed 4- and 2-hydroxyestradiol with yields of 45 and 16%, respectively. A preparative-scale incubation was conducted in 2 liters of medium containing 1 g of 17 beta-estradiol as substrate. 4-Hydroxyestradiol was isolated and identified by proton nuclear magnetic resonance and high-resolution mass spectrometry. Ascorbic acid was added to microbial reaction mixtures as an antioxidant to prevent the decomposition of unstable catechol estrogen metabolites. The microbial transformation of 17 beta-estradiol by A. alliaceus provides an efficient one-step method for the preparation of catechol estrogens. PMID:3994364

  11. EFFECTS OF ETHINYL ESTRADIOL ON GONDAL DEVELOPMENT AND PATHOLOGY IN CUNNER, TAUTOGOLABRUS ADSPERSUS

    EPA Science Inventory

    The intent of this study was to determine histopathologically the effect of ethinyl estradiol (EE2) on gonadal development, liver and kidney condition in reproductively active cunner, Tautogolabrus adspersus. Reproductively active cunner were treated by implanting EE2 in a slow r...

  12. Estradiol impairs response inhibition in young and middle-aged, but not old rats

    PubMed Central

    Wang, Victor C.; Neese, Steven L.; Korol, Donna L.; Schantz, Susan L.

    2011-01-01

    Estrogens have been shown to have a strong influence on such cognitive domains as spatial memory, response learning, and several tasks of executive function, including both working memory and attention. However, the effects of estrogens on inhibitory control and timing behavior, both important aspects of executive function, have received relatively little attention. We examined the effects of estradiol on inhibitory control and timing using a differential reinforcement of low rates of responding (DRL) task. Ovariectomized young (3 month), middle-aged (12 month), and old (18 month) Long-Evans rats received 5% or 10% 17β-estradiol in cholesterol vehicle or cholesterol vehicle alone via Silastic implants and were tested on a DRL task requiring them to wait 15 seconds between lever presses to receive a food reinforcer. The ratio of reinforced to non-reinforced lever presses did not differ across age in the cholesterol vehicle group. Conversely, 17β-estradiol impaired learning of the DRL task in young and middle-aged rats, but the learning of old rats was not impaired relative to vehicle controls following either 5% or 10% 17β-estradiol treatment. Overall, old rats also made fewer lever presses than both the young and middle-aged rats. These results provide new evidence that estrogens impair inhibitory control, an important aspect of self regulation, and add to existing evidence that estrogens differentially affect cognition at different ages. PMID:21281713

  13. Effects of bromocriptine on (/sup 3/H)estradiol binding in cytosol of anterior pituitary

    SciTech Connect

    De Nicola, A.F.; Weisenberg, L.S.; Arakelian, M.C.; Libertun, C.

    1981-07-01

    The hypothalamus may control hormone receptors in the anterior pituitary either by a direct trophic effect or indirectly by regulation of serum pituitary hormone levels. Rats whose medial basal hypothalamus had been destroyed in order to suppress neural control of the gland showed a reduction in (/sup 3/H)estradiol binding in the anterior pituitary and high serum PRL levels; both changes were reversed by treatment of the lesioned rats with daily injections of bromocriptine, a dopamine agonist. In nonlesioned animals, the same treatment did not modify significantly those parameters. In another hyperprolactinemic model (rats with anterior pituitaries transplanted under the kidney capsule), (/sup 3/H)estradiol binding by the in situ pituitaries of the host rats was similar to that in the nongrafted controls. These results suggest that changes due to median eminence lesion are reversible and that bromocriptine is able to act as a substitutive therapy which restores binding of estradiol in glands whose receptors have been decreased by the effect of the lesion. High PRL levels due to pituitary transplant do not account for the observed changes in the pituitary estradiol binding.

  14. Toxicity of 17 {beta}-estradiol and dibutyl-n-phthalate to Japanese medaka (Oryzias latipes)

    SciTech Connect

    Patvna, P.J.; Cooper, K.R. |

    1995-12-31

    Phthalate esters are ubiquitous environmental contaminants that are hypothesized to cause developmental toxicity in aquatic organisms via an estrogenic mechanism. Japanese medaka embryos and larvae provide an excellent model for the study of toxicant effects on embryonic development. The following groups were examined (N = 10--20): a non-treatment control, a vehicle control, 17 {beta}-estradiol and Dibutyl-n-phthalate, in individual glass vials. The medaka embryos were treated beginning at the blastula stage, for ten days. At day 10, embryos were changed into fresh rearing solution. The embryos were observed daily, until three days post-hatching, for toxic developmental effects. Exposure to 17 {beta}-estradiol caused urinary bladder lesions at the lowest doses tested. At concentrations {le} 3 {micro}M/0.82 ppm, 17 {beta}-estradiol caused inhibition of swim bladder inflation, pericardial edema, and marked cachexia. Dibutyl-n-phthalate caused pronounced enlargement of the urinary bladder. No other gross lesions were observed. Both 17 {beta}-estradiol and Dibutyl-n-phthalate caused effects on the urinary tract which will be characterized at the light microscopic level. The lesions observed in the embryo medaka following Dibutyl-n-phthalate exposure were at or below water solubility and are in agreement with previously reported toxic levels.

  15. Pregnancy rates after ewes were treated with estradiol-17beta and oxytocin.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cervical dilation may improve transcervical sheep embryo-transfer procedures, if the cervical dilation method does not reduce pregnancy rates. This experiment was conducted to determine whether estradiol-17beta-oxytocin treatment, which dilates the cervix in luteal-phase ewes, affects pregnancy rat...

  16. Changes in salivary estradiol predict changes in women's preferences for vocal masculinity.

    PubMed

    Pisanski, Katarzyna; Hahn, Amanda C; Fisher, Claire I; DeBruine, Lisa M; Feinberg, David R; Jones, Benedict C

    2014-08-01

    Although many studies have reported that women's preferences for masculine physical characteristics in men change systematically during the menstrual cycle, the hormonal mechanisms underpinning these changes are currently poorly understood. Previous studies investigating the relationships between measured hormone levels and women's masculinity preferences tested only judgments of men's facial attractiveness. Results of these studies suggested that preferences for masculine characteristics in men's faces were related to either women's estradiol or testosterone levels. To investigate the hormonal correlates of within-woman variation in masculinity preferences further, here we measured 62 women's salivary estradiol, progesterone, and testosterone levels and their preferences for masculine characteristics in men's voices in five weekly test sessions. Multilevel modeling of these data showed that changes in salivary estradiol were the best predictor of changes in women's preferences for vocal masculinity. These results complement other recent research implicating estradiol in women's mate preferences, attention to courtship signals, sexual motivation, and sexual strategies, and are the first to link women's voice preferences directly to measured hormone levels.

  17. Effect of Dietary Fiber Intake on Lipoprotein Cholesterol Levels Independent of Estradiol in Healthy Premenopausal Women

    PubMed Central

    Mumford, Sunni L.; Schisterman, Enrique F.; Siega-Riz, Anna Maria; Gaskins, Audrey J.; Wactawski-Wende, Jean; VanderWeele, Tyler J.

    2011-01-01

    High-fiber diets are associated with improved lipid profiles. However, pre- and postmenopausal women respond differently to fiber intake, suggesting that endogenous estradiol mediates the effect. The authors' objective was to determine the direct effect of fiber intake on lipoprotein cholesterol levels independent of estradiol among premenopausal women. The BioCycle Study, a prospective cohort study conducted at the State University of New York at Buffalo from 2005 to 2007, followed 259 healthy women for up to 2 complete menstrual cycles. Serum lipoprotein and hormone levels were measured at 16 visits timed using fertility monitors. Fiber intake was assessed by 8 24-hour recalls. Marginal structural models with inverse probability weights for both lipoprotein and estradiol levels were used to estimate controlled direct effects of the highest category of fiber intake (≥22 g/day vs. <22 g/day) while accounting for age, body mass index, total energy, vitamin E intake, physical activity, luteinizing hormone, follicle-stimulating hormone, and progesterone. Reductions were observed in total and low density lipoprotein cholesterol in women with higher fiber intakes. Direct effects were greater than total effects. These analyses suggested that estradiol mediates at least part of the association between fiber and cholesterol among premenopausal women. More research is needed to elucidate the biologic mechanisms driving these associations. PMID:21148240

  18. 17ß-Estradiol Is Necessary for Extinction of Cocaine Seeking in Female Rats

    ERIC Educational Resources Information Center

    Twining, Robert C.; Tuscher, Jennifer J.; Doncheck, Elizabeth M.; Frick, Karyn M.; Mueller, Devin

    2013-01-01

    Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17ß-estradiol (E[subscript 2]) affects expression and extinction of cocaine seeking in female rats. Using a…

  19. Determination of 17 β-Estradiol in Rabbit Plasma by Gas Chromatography with Flame Ionization Detection

    PubMed Central

    Yilmaz, B; Kadioglu, Y.

    2012-01-01

    This article describes gas chromatography-flame ionization detection method for determination of 17 β-estradiol in rabbit plasma. 17 β-estradiol and internal standard progesterone were extracted from plasma using liquid–liquid extraction method. Linearity was found between 0.25 and 20 μg/ml (r2=0.994) for plasma samples. Intra-day and inter-day precision, expressed as the relative standard deviation were less than 5.5%, and accuracy (relative error) was less than 3.5%. The mean recovery of 17 β-estradiol samples was 94.4%. The limits of detection and quantification of method for plasma samples were 0.10 μg/ml and 0.15 μg/ml, respectively. Also, clinically used other 10 drugs were investigated to check for potential interferences and the method was successfully applied to the determination of 17 β-estradiol in New Zealand white rabbits. PMID:23439655

  20. Prepartal concentration of estradiol-17beta in heifers with stillborn calves.

    PubMed

    Sorge, U S; Kelton, D F; Staufenbiel, R

    2008-04-01

    This study was conducted to investigate hormonal imbalances preceding stillbirths and dystocia in primiparous heifers. The study was conducted between 2003 and 2004 on a German dairy farm, including 433 heifers. Starting 3 wk before calving, a weekly blood sample was collected. At calving, another blood sample was obtained, and the calving ease (grade 0 = unassisted to grade 2 = heavy pull with mechanical calf puller), sex, birth weight, as well as vitality status (stillborn, alive) of the calf were recorded. The blood serum was analyzed for estradiol-17beta and progesterone concentration. At parturition, the measured estradiol-17beta concentration was greater in heifers delivering bulls than in those with female calves and was increasing with greater birth weight of the calf and increasing calving difficulty score. Already 2 wk before calving, the serum estradiol-17beta concentration was significantly smaller in heifers with stillborn than live calves. On the other hand, the progesterone concentration was greater 2 wk before calving in heifers with stillborn calves, but it was unaffected by the birth weight or sex of the calf or the calving difficulty score. Stillborn and live calves did not differ in birth weight or pregnancy duration. The smaller estradiol-17beta concentrations of the heifers with stillborn calves could indicate an abnormality of the placenta or an abnormality of hormonal signals from the calf to the placenta in the weeks before the calving.

  1. Sexual Function in Women on Estradiol or Venlafaxine for Hot Flushes: A Randomized Controlled Trial

    PubMed Central

    Reed, Susan D.; Mitchell, Caroline M.; Joffe, Hadine; Cohen, Lee; Shifren, Jan L.; Newton, Katherine M.; Freeman, Ellen W.; Larson, Joseph C.; Manson, JoAnn E.; LaCroix, Andrea Z.; Guthrie, Katherine A.

    2014-01-01

    Objective To evaluate sexual function in midlife women taking low-dose oral estradiol or venlafaxine for hot flushes. Methods In an 8-week randomized controlled trial among women aged 40-62 years, sexual function was compared between oral estradiol 0.5 mg/day or venlafaxine 75 mg/day (both compared with placebo). Measures included composite and 6 domain scores from the Female Sexual Function Index (FSFI) and sexually related personal distress. Results Participants were aged 54.6 (standard deviation [SD] 3.8) years, 59% Caucasian, with 8.1 (SD 5.3) daily hot flushes. Median composite baseline FSFI score was 16.3 (SD 11.9, n=256) for all women and 21.7 (SD 9.3, n=198) among sexually active women. Composite mean FSFI change from baseline to week-8 was 1.4 (95% Confidence Interval [CI] -0.4, 3.2) for estradiol, 1.1 (95% CI -0.5, 2.7) for venlafaxine and -0.3 (95% CI -1.6, 1.0) for placebo. Composite FSFI and sexually-related distress change from baseline did not differ between estradiol and placebo (p= 0.38, p=0.30) or venlafaxine and placebo (p=0.79, p=0.48). Among sexually active women, FSFI domain score change from baseline differences (active compared with placebo) in desire was 0.3 (95% CI 0.0, 0.6) for estradiol; -0.6 (95% CI -1.2, 0.0) in orgasm for venlafaxine, and 0.9 (95% CI 0.2, 1.6) in penetration pain for venlafaxine. No women reported adverse events related to sexual dysfunction. Conclusions Overall sexual function among nondepressed midlife women experiencing hot flushes did not change over 8-weeks with low-dose oral estradiol or venlafaxine (compared with placebo), although subtle increase in desire (estradiol), and decreases in orgasm and pain (venlafaxine) may exist. PMID:25004335

  2. Diethylstilbestrol can effectively accelerate estradiol-17-O-glucuronidation, while potently inhibiting estradiol-3-O-glucuronidation

    SciTech Connect

    Zhu, Liangliang; Xiao, Ling; Xia, Yangliu; Zhou, Kun; Wang, Huili; Huang, Minyi; Ge, Guangbo; Wu, Yan; Wu, Ganlin; Yang, Ling

    2015-03-01

    This in vitro study investigates the effects of diethylstilbestrol (DES), a widely used toxic synthetic estrogen, on estradiol-3- and 17-O- (E2-3/17-O) glucuronidation, via culturing human liver microsomes (HLMs) or recombinant UDP-glucuronosyltransferases (UGTs) with DES and E2. DES can potently inhibit E2-3-O-glucuronidation in HLM, a probe reaction for UGT1A1. Kinetic assays indicate that the inhibition follows a competitive inhibition mechanism, with the Ki value of 2.1 ± 0.3 μM, which is less than the possible in vivo level. In contrast to the inhibition on E2-3-O-glucuronidation, the acceleration is observed on E2-17-O-glucuronidation in HLM, in which cholestatic E2-17-O-glucuronide is generated. In the presence of DES (0–6.25 μM), K{sub m} values for E2-17-O-glucuronidation are located in the range of 7.2–7.4 μM, while V{sub max} values range from 0.38 to 1.54 nmol/min/mg. The mechanism behind the activation in HLM is further demonstrated by the fact that DES can efficiently elevate the activity of UGT1A4 in catalyzing E2-17-O-glucuronidation. The presence of DES (2 μM) can elevate V{sub max} from 0.016 to 0.81 nmol/min/mg, while lifting K{sub m} in a much lesser extent from 4.4 to 11 μM. Activation of E2-17-O-glucuronidation is well described by a two binding site model, with K{sub A}, α, and β values of 0.077 ± 0.18 μM, 3.3 ± 1.1 and 104 ± 56, respectively. However, diverse effects of DES towards E2-3/17-O-glucuronidation are not observed in liver microsomes from several common experimental animals. In summary, this study issues new potential toxic mechanisms for DES: potently inhibiting the activity of UGT1A1 and powerfully accelerating the formation of cholestatic E2-17-O-glucuronide by UGT1A4. - Highlights: • E2-3-O-glucuronidation in HLM is inhibited when co-incubated with DES. • E2-17-O-glucuronidation in HLM is stimulated when co-incubated with DES. • Acceleration of E2-17-O-glucuronidationin in HLM by DES is via activating the

  3. Naturally-occurring estradiol-17{beta}-fatty acid esters, but not estradiol-17{beta}, preferentially induce mammary tumorigenesis in female rats: Implications for an important role in human breast cancer

    SciTech Connect

    Mills, Laura H.; Yu Jina; Xu Xiaomeng; Lee, Anthony J.; Zhu Baoting

    2008-06-15

    Because mammary glands are surrounded by adipose tissues, we hypothesize that the ultra-lipophilic endogenous estrogen-17{beta}-fatty acid esters may have preferential hormonal and carcinogenic effects in mammary tissues compared to other target organs (such as the uterus and pituitary). This hypothesis is tested in the present study. We found that all 46 rats implanted with an estradiol-17{beta} pellet developed large pituitary tumors (average weight = 251 {+-}103 mg) and had to be terminated early, but only 48% of them developed mammary tumors. In addition, approximately one-fourth of them developed a huge uterus. In the 26 animals implanted with a mixture containing estradiol-17{beta}-stearate and estradiol-17{beta}-palmitate (two representative estradiol-17{beta}-fatty acid esters) or in the 29 animals implanted with estradiol-17{beta}-stearate alone (in the same molar dose as estradiol-17{beta}), 73% and 79%, respectively, of them developed mammary tumors, whereas only 3 or 2 animals, respectively, had to be terminated early due to the presence of a large pituitary tumor. Both tumorous and normal mammary tissues contained much higher levels of estrogen esterase than other tissues, which catalyzes the releases of bioactive estrogens from their fatty acid esters. In conclusion, while estradiol-17{beta} is much stronger in inducing pituitary tumor (100% incidence) than mammary tumor, estradiol-17{beta}-fatty acid esters have a higher efficacy than estradiol-17{beta} in inducing mammary tumor and yet it only has little ability to induce uterine out-growth and pituitary tumorigenesis. This study establishes the endogenous estrogen-17{beta}-fatty acid esters as preferential inducers of mammary tumorigenesis.

  4. Effects of estradiol and IGF-1 on the sodium calcium exchanger in rat cultured cortical neurons.

    PubMed

    Sánchez, Julio C; López-Zapata, Diego F; Francis, Liliana; De Los Reyes, Lina

    2011-05-01

    The Na(+)/Ca(2+) exchanger (NCX) is an important bidirectional transporter of calcium in neurons and has been shown to be involved in neuroprotection. Calcium can activate a number of cascades that can result in apoptosis and cell death, and NCX is a key factor in regulating the cytoplasmic concentration of this ion. 17-β-estradiol and insulin-like growth factor 1 (IGF-1) are known neuroprotective hormones with interacting mechanisms and effects on intracellular calcium; however, their relationship with the NCX has not been explored. In this article, the effects of these two hormones on neuronal NCX were tested using the whole-cell patch clamp technique on rat primary culture neurons. Both 17-β-estradiol and IGF-1 produced an increase in the NCX-mediated inward current and a decrease in the NCX-mediated outward current. However, the IGF-1 effect was lower than that of 17-β-estradiol, and the effect of both agents together was greater than the sum of each agent alone. Neither of the agents affected the pattern of regulation by extracellular or intrapipette calcium. Inhibitors of the IGF-1 and 17-β-estradiol receptors and inhibitors of the main signaling pathways failed to change the observed effects, indicating that these actions were not mediated by the classical receptors of these hormones. These effects on the NCX could be a mechanism explaining the neuroprotective actions of 17-β-estradiol and IGF-1, and these findings could help researchers to understand the role of the NCX in neuroprotection.

  5. Estradiol-induced synaptic remodeling of tyrosine hydroxylase immunopositive neurons in the rat arcuate nucleus.

    PubMed

    Csakvari, Eszter; Kurunczi, Anita; Hoyk, Zsofia; Gyenes, Andrea; Naftolin, Frederick; Parducz, Arpad

    2008-08-01

    Gonadal steroids induce synaptic plasticity in several areas of the adult nervous system. In the arcuate nucleus of adult female rats, 17beta-estradiol triggers synaptic remodeling, resulting in a decrease in the number of inhibitory synaptic inputs, an increase in the number of excitatory synapses, and an enhancement of the frequency of neuronal firing. In the present paper, we studied the specificity of hormonal effects by determining the changes in synaptic connectivity of tyrosine hydroxylase (TH) immunoreactive (IR) neurons in the arcuate nucleus. We combined pre-embedding TH and post-embedding gamma-aminobutyric acid (GABA) immunostaining, and performed unbiased stereological measurements in gonadectomized and 17beta-estradiol-treated rats. We conclude that the synaptic connectivity of the TH-IR neurons is different from the other, nonlabeled population, and the response to estradiol is not uniform. TH-IR (dopaminergic) arcuate neurons of both male and female rats have more GABAergic (inhibitory) axosomatic inputs than the nondopaminergic population. Our study shows that the effect of 17beta-estradiol is sex and cell specific in the sense that not all arcuate neurons are affected by the structural synaptic remodeling. In ovariectomized females hormone treatment decreased the numerical density of GABAergic axosomatic synapses on TH-IR, but not on nondopaminergic, neurons, whereas in orchidectomized males, 17beta-estradiol treatment increased inhibitory synapses onto nondopaminergic neurons but did not affect the number of inhibitory terminals onto TH-IR neurons. The hormone-induced plastic changes in synaptic connectivity of TH-IR neurons may serve as the morphological basis for the cyclical regulation of the anterior pituitary.

  6. Analyzing the influence of BDNF heterozygosity on spatial memory response to 17β-estradiol.

    PubMed

    Wu, Y W C; Du, X; van den Buuse, M; Hill, R A

    2015-01-20

    The recent use of estrogen-based therapies as adjunctive treatments for the cognitive impairments of schizophrenia has produced promising results; however the mechanism behind estrogen-based cognitive enhancement is relatively unknown. Brain-derived neurotrophic factor (BDNF) regulates learning and memory and its expression is highly responsive to estradiol. We recently found that estradiol modulates the expression of hippocampal parvalbumin-positive GABAergic interneurons, known to regulate neuronal synchrony and cognitive function. What is unknown is whether disruptions to the aforementioned estradiol-parvalbumin pathway alter learning and memory, and whether BDNF may mediate these events. Wild-type (WT) and BDNF heterozygous (+/-) mice were ovariectomized (OVX) at 5 weeks of age and simultaneously received empty, estradiol- or progesterone-filled implants for 7 weeks. At young adulthood, mice were tested for spatial and recognition memory in the Y-maze and novel-object recognition test, respectively. Hippocampal protein expression of BDNF and GABAergic interneuron markers, including parvalbumin, were assessed. WT OVX mice show impaired performance on Y-maze and novel-object recognition test. Estradiol replacement in OVX mice prevented the Y-maze impairment, a Behavioral abnormality of dorsal hippocampal origin. BDNF and parvalbumin protein expression in the dorsal hippocampus and parvalbumin-positive cell number in the dorsal CA1 were significantly reduced by OVX in WT mice, while E2 replacement prevented these deficits. In contrast, BDNF(+/-) mice showed either no response or an opposite response to hormone manipulation in both behavioral and molecular indices. Our data suggest that BDNF status is an important biomarker for predicting responsiveness to estrogenic compounds which have emerged as promising adjunctive therapeutics for schizophrenia patients.

  7. Estradiol-induced promotion of hepatocarcinogenesis in medaka: Relationship of foci of cellular alteration to neoplasia

    SciTech Connect

    Cooke, J.B.; Hinton, D.E.

    1995-12-31

    In some laboratory and field studies, female fish have higher prevalences of liver tumors than do males. The authors hypothesize gender and site-specific differences in prevalence are due to variable exposures of previously initiated fish to tumor modulating compounds. Estradiol, a growth promoter, increases incidences of hepatic tumors in carcinogen-treated rainbow trout and medaka (Oryzias latipes). Estradiol also increases incidences of hepatic foci of cellular alteration (FCA) in medaka. FCA are found in subadults of tumor-bearing feral populations. Lack of knowledge about the relationship of various phenotypes of FCA to eventual tumors, however, has prevented use of FCA as a biomarker. The authors examined fate and growth of liver FCA using a 2-step, initiation-promotion protocol. Three week old medaka were exposed to 200 ppm diethylnitrosamine (DEN) for 24 hr. and then fed 0.1 ppm 17-{beta}-estradiol (E2) continuously through sampling at weeks 4--26. Percent volume of FCA and morphometric characteristics of normal and focal hepatocytes, including numerical density and average hepatocyte volume were quantified using computer-assisted stereology. E2 increased percentage of liver occupied by DEN-initiated amphophilic, basophilic and eosinophilic FCA in both sexes. Focal parameters of young, DEN-initiated and estradiol-treated medaka were not reached until much later in fish given only DEN. Non-focal hepatocytes in estradiol-treated medaka were smaller and more numerous than in DEN-only counterparts. Morphometric analysis is quantitatively tracking the fate of specific phenotypes of FCA to determine their role in progression to cancer.

  8. Localization of neuropeptide-Y immunoreactivity in estradiol-concentrating cells in the hypothalamus

    SciTech Connect

    Sar, M.; Sahu, A.; Crowley, W.R.; Kalra, S.P. )

    1990-12-01

    Considerable evidence shows that gonadal steroids exert a facilitatory influence on levels and release of neuropeptide-Y (NPY) from the hypothalamus. However, it is not known whether gonadal steroids act directly on NPY-producing cells in the arcuate nucleus (ARC) of the hypothalamus to produce these facilitatory effects on NPY or whether they act on other cells that have a modulatory influence via synapses on ARC NPY cells. We applied the combined method of steroid autoradiography and immunocytochemistry to assess the localization of (3H)estradiol in relation to NPY-producing cells in the hypothalamus. Rats (n = 6) were bilaterally ovariectomized and injected intracerebroventricularly with colchicine. Twenty-four hours later each rat received an iv injection of 17 beta-(2,4,6,7,16,17(-3)H)estradiol (SA, 166 Ci/mmol) at a dose of 5.0 micrograms/kg BW. One hour after the injection of (3H)estradiol, the rats were perfused with 4% paraformaldehyde; brains were removed, frozen in isopentane precooled in liquid nitrogen (-190 C), sectioned, and processed for autoradiography. The autoradiograms were then incubated with specific antibodies for NPY immunostaining by the avidin-biotin-peroxidase method. The results revealed NPY-immunopositive cells in the ARC, striatum, hippocampus, amygdala, and cerebral cortex and a few cells in the median eminence. NPY-immunoreactive fibers were also detected in the internal layer of the median eminence. The largest number of neurons showing NPY immunoreactivity in the cytoplasm was detected in the ARC, and only in this nucleus did we observed colocalization of (3H)estradiol and NPY immunoreactivity in neurons. A population of NPY-immunopositive cells in the ARC (10-20%) exhibited nuclear (3H)estradiol; the majority of these cells were located in the lateral and ventral portions of the ARC.

  9. Rapid Estradiol Modulation of Neuronal Connectivity and Its Implications for Disease

    PubMed Central

    Srivastava, Deepak P.; Penzes, Peter

    2011-01-01

    Estrogens have multiple actions in the brain including modulating synaptic plasticity, connectivity, and cognitive behaviors. While the classical view of estrogens are as endocrine signals, whose effects manifest via the regulation of gene transcription, mounting evidence has been presented demonstrating that estrogens have rapid effects within specific areas of the brain. The emergence that 17 β-estradiol can be produced locally in the brain which can elicit rapid (within minutes) cellular responses has led to its classification as a neurosteroid. Moreover, recent studies have also begun to detail the molecular and cellular underpinnings of how 17 β-estradiol can rapidly modulate spiny synapses (dendritic spines). Remodeling of dendritic spines is a key step in the rewiring of neuronal circuitry thought to underlie the processing and storage of information in the forebrain. Conversely, abnormal remodeling of dendritic spines is thought to contribute to a number of psychiatric and neurodevelopmental disorders. Here we review recent molecular and cellular work that offers a potential mechanism of how 17 β-estradiol may modulate synapse structure and function of cortical neurons. This mechanism allows cortical neurons to respond to activity-dependent stimuli with greater efficacy. In turn this form of plasticity may provide an insight into how 17 β-estradiol can modulate the rewiring of neuronal circuits, underlying its ability to influencing cortically based behaviors. We will then go on to discuss the potential role of 17 β-estradiol modulation of neural circuits and its potential relevance for the treatment of psychiatric and neurodevelopmental disorders. PMID:22654827

  10. Analysis of 19 PCB congeners in catfish tissue using a modified QuEChERS method with GC-MS/MS.

    PubMed

    Chamkasem, Narong; Lee, Sookwang; Harmon, Tiffany

    2016-02-01

    A simple approach to determine 19 PCB congeners in catfish tissue was presented. A modified QuEChERS method employing high solvent to sample ratio 10:1 was used to improve the extraction recovery of 19 PCB congeners. After salting out by shaking with anhydrous magnesium sulfate and sodium chloride, 1 mL of acetonitrile extract was pipetted into a 2-mL centrifuge tube containing anhydrous magnesium sulfate, primary secondary amine sorbent, and C-18 sorbent. The tube was then shaken and centrifuged to absorb fat and fatty acid residue present in the acetonitrile extract. The acetonitrile extract was analyzed by GC-MS/MS. The excellent sensitivity of GC-MS/MS allows for the direct injection of the samples to detect the low level of the PCB congeners. The method therefore is high throughput, uses fewer consumable lab supplies, and provides excellent sensitivity with an LOQ below 1 ng/g. PMID:26304427

  11. Speciation and quantitation of Aroclors based on PCB congener data: Application to California mussels and white croaker. [Mytilus californianus; Genyonemus lineatus

    SciTech Connect

    Draper, W.M. ); Koszdin, S. )

    1991-08-01

    A procedure for speciation and quantitation of Aroclors in capillary gas-liquid chromatography electron capture detector (GC-ECD) chromatograms is described. Four pentachlorobiphenyls (IUPAC no. PCB-87, -110, -118, and -105) and three heptachlorobiphenyls (PCB-183, -180, and -170) are used as markers of Aroclor 1254 and Aroclor 1260, respectively. The Aroclor content of samples is estimated by comparing the cogener composition with USEPA Aroclor reference materials. In this study, the selected congener approach to Aroclor determination is applied to both California marine mussels (Mytilus californianus and M. Edulis) and white croaker (Genyonemus lineatus) muscle. Both Aroclor 1254 and Aroclor 1260 were present in these species, and the congener patterns matched the Aroclor reference materials closely. In cases where reporting Aroclors is not appropriate, e.g., highly weathered samples, the method also provides PCB congener data.

  12. Congener-specific carbon isotopic analysis of technical PCB and PCN mixtures using two-dimensional gas chromatography-isotope ratio mass spectrometry.

    PubMed

    Horii, Yuichi; Kannan, Kurunthachalam; Petrick, Gert; Gamo, Toshitaka; Falandysz, Jerzy; Yamashita, Nobuyoshi

    2005-06-01

    Analysis of stable carbon isotope fractionation is a useful method to study the sources and fate of anthropogenic organic contaminants such as polychlorinated biphenyls (PCBs) in the environment. To evaluate the utility of carbon isotopes, determination of isotopic ratios of 13C/12C in source materials, for example, technical PCB preparations, is needed. In this study, we determined delta13C values of 31 chlorobiphenyl (CB) congeners in 18 technical PCB preparations and 15 chloronaphthalene (CN) congeners in 6 polychlorinated naphthalene preparations using two-dimensional gas chromatography-combustion furnace-isotope ratio mass spectrometry (2DGC-C-IRMS). Development of 2DGC-IRMS enabled improved resolution and sensitivity of compound-specific carbon isotope analysis (CSIA) of CB or CN congeners. Delta13C values of PCB congeners ranged from -34.4 (Delors) to -22.0/1000 (Sovol). Analogous PCB preparations with similar chlorine content, but different geographical origin, had different delta13C values. PCB preparations from Eastern European countries--Delors, Sovol, Trichlorodiphenyl, and Chlorofen--had distinct delta13C values. PCB mixtures showed increased 13C depletion with increasing chlorine content. Delta13C values for individual CB congeners varied depending on the degree of chlorination in technical mixtures. Delta13C values of CN congeners in Halowaxes ranged from -26.3 to -21.7/1000 and these values are within the ranges observed for PCBs. This study establishes the range of delta13C values in technical PCB and PCN preparations, which may prove to be useful in the determination of sources of these compounds in the environment. This is the first study to employ 2DGC-IRMS analysis of delta13C values in technical PCB and PCN preparations.

  13. Preparation of 17β-estradiol-imprinted material by surface-initiated atom transfer radical polymerization and its application.

    PubMed

    Gong, Yanru; Niu, Yuling; Gong, Xiaohan; Ma, Meihua; Ren, Xiaowei; Zhu, Weihua; Luo, Ruiming; Gong, Bolin

    2015-04-01

    A novel 17β-estradiol molecularly imprinted polymer was grafted onto the surface of initiator-immobilized silica by surface-initiated atom transfer radical polymerization. The resulting molecularly imprinted polymer was characterized by elemental analysis and thermogravimetric analysis. The binding property of molecularly imprinted polymer for 17β-estradiol was also studied with both static and dynamic methods. The results showed that the molecularly imprinted polymer possessed excellent recognition capacity for 17β-estradiol (180.65 mg/g at 298 K), and also exhibited outstanding selectivity for 17β-estradiol over the other competitive compounds (such as testosterone and progesterone). Then, the determination of trace 17β-estradiol in beef samples was successfully developed by using molecularly imprinted polymer solid-phase extraction coupled with high-performance liquid chromatography. The limit of detection was 0.25 ng/mL, and the amount of 17β-estradiol in beef samples was detected at 2.83 ng/g. This work proposed a sensitive, rapid, reliable, and convenient approach for the determination of trace 17β-estradiol in complicated beef samples. PMID:25619938

  14. Di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate inhibit growth and reduce estradiol levels of antral follicles in vitro

    SciTech Connect

    Gupta, Rupesh K.; Singh, Jeffery M.; Leslie, Tracie C.; Meachum, Sharon; Flaws, Jodi A.; Yao, Humphrey H-C

    2010-01-15

    Any insult that affects survival of ovarian antral follicles can cause abnormal estradiol production and fertility problems. Phthalate esters (PEs) are plasticizers used in a wide range of consumer and industrial products. Exposure to these chemicals has been linked to reduced fertility in humans and animal models. Di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) decrease serum estradiol levels and aromatase (Arom) expression, prolong estrous cycles, and cause anovulation in animal and culture models. These observations suggest PEs directly target antral follicles. We therefore tested the hypothesis that DEHP (1-100 mug/ml) and MEHP (0.1-10 mug/ml) directly inhibit antral follicular growth and estradiol production. Antral follicles from adult mice were cultured with DEHP or MEHP, and/or estradiol for 96 h. During culture, follicle size was measured every 24 h as a measurement of follicle growth. After culture, media were collected for measurement of estradiol levels and follicles were subjected to measurement of cylin-D-2 (Ccnd2), cyclin-dependant-kinase-4 (Cdk4), and Arom. We found that DEHP and MEHP inhibited growth of follicles and decreased estradiol production compared to controls at the highest doses. DEHP and MEHP also decreased mRNA expression of Ccnd2, Cdk4, and Arom at the highest dose. Addition of estradiol to the culture medium prevented the follicles from DEHP- and MEHP-induced inhibition of growth, reduction in estradiol levels, and decreased Ccnd2 and Cdk4 expression. Collectively, our results indicate that DEHP and MEHP may directly inhibit antral follicle growth via a mechanism that partially includes reduction in levels of estradiol production and decreased expression of cell cycle regulators.

  15. Estradiol promotes pentose phosphate pathway addiction and cell survival via reactivation of Akt in mTORC1 hyperactive cells.

    PubMed

    Sun, Y; Gu, X; Zhang, E; Park, M-A; Pereira, A M; Wang, S; Morrison, T; Li, C; Blenis, J; Gerbaudo, V H; Henske, E P; Yu, J J

    2014-05-15

    Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease that can lead to respiratory failure. LAM cells typically have inactivating TSC2 mutations, leading to mTORC1 activation. The gender specificity of LAM suggests that estradiol contributes to disease development, yet the underlying pathogenic mechanisms are not completely understood. Using metabolomic profiling, we identified an estradiol-enhanced pentose phosphate pathway signature in Tsc2-deficient cells. Estradiol increased levels of cellular NADPH, decreased levels of reactive oxygen species, and enhanced cell survival under oxidative stress. Mechanistically, estradiol reactivated Akt in TSC2-deficient cells in vitro and in vivo, induced membrane translocation of glucose transporters (GLUT1 or GLUT4), and increased glucose uptake in an Akt-dependent manner. (18)F-FDG-PET imaging demonstrated enhanced glucose uptake in xenograft tumors of Tsc2-deficient cells from estradiol-treated mice. Expression array study identified estradiol-enhanced transcript levels of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway. Consistent with this, G6PD was abundant in xenograft tumors and lung metastatic lesions of Tsc2-deficient cells from estradiol-treated mice. Molecular depletion of G6PD attenuated estradiol-enhanced survival in vitro, and treatment with 6-aminonicotinamide, a competitive inhibitor of G6PD, reduced lung colonization of Tsc2-deficient cells. Collectively, these data indicate that estradiol promotes glucose metabolism in mTORC1 hyperactive cells through the pentose phosphate pathway via Akt reactivation and G6PD upregulation, thereby enhancing cell survival under oxidative stress. Interestingly, a strong correlation between estrogen exposure and G6PD was also found in breast cancer cells. Targeting the pentose phosphate pathway may have therapeutic benefit for LAM and possibly other hormonally dependent neoplasms.

  16. Effects of estradiol on food intake and meal patterns for diets that differ in flavor and fat content.

    PubMed

    Butera, Peter C; Wojcik, Danielle M; Clough, Shannon J

    2010-01-12

    Apart from the well known inhibitory effects of estradiol on food intake, meal size, and body weight in female rats that have been documented over the past thirty years, a more recent report presents the opposite finding; that a large dose of estradiol can increase food intake and weight gain in gonadally intact female rats presented with a palatable diet. The purpose of the present experiment was to further examine this hypothesis by evaluating the ability of estradiol to influence feeding behavior in ovariectomized rats presented with diets that differ in flavor and fat content. Female rats were given a cyclic regimen of estradiol benzoate treatment (5.0 or 20.0 microg) or the oil vehicle and were presented with the standard chow diet or a diet with a higher fat content and chocolate flavor. Food intake, meal size, and meal number were monitored three days after the first injection of estradiol or oil. Compared to the chow diet, food intake increased when animals had access to the chocolate/fat diet during the vehicle treatment condition. Both doses of estradiol significantly decreased food intake, meal size, and body weight gain when animals were presented with either the standard chow diet or the chocolate/fat diet. These findings indicate that estradiol does not stimulate the intake of a palatable diet in ovariectomized rats, and suggest that previous results showing that estradiol enhanced eating and weight gain stemmed from a disruption of the hypothalamic-pituitary-gonadal axis when intact females received a large dose of exogenous estradiol.

  17. Serum estradiol concentration required to maintain body weight, attractivity, proceptivity, and receptivity in the ovariectomized female rat.

    PubMed

    Albert, D J; Jonik, R H; Gorzalka, B B; Newlove, T; Webb, B; Walsh, M L

    1991-02-01

    Female hooded rats (230 to 260 g) were ovariectomized and given a subcutaneous implant of an estradiol-filled Silastic tube. The length of the tube was varied in order to produce a variety of serum estradiol levels. In the first experiment, animals were weighed over a 6-week period following surgery and then tested for sexual responsiveness to a male. The results demonstrated that ovariectomized females with an implant maintaining a serum estradiol concentration at about 15 pg/ml maintained body weight at the same level as that of intact females. A smaller implant gave rise to a higher weight gain and a larger implant to a lower weight gain. All implants resulted in a continuous state of receptivity. In a second experiment, ovariectomized females were implanted with smaller estradiol-filled implants in order to determine the threshold for maintaining proceptivity and receptivity. The results indicated that with a serum estradiol concentration below 15 pg/ml, the frequency of lordosis and of ear wiggling and darting decreased. Progesterone injections facilitated both proceptive and receptive behavior. In addition, following progesterone injections, the time required for a male to mount a female 10 times was decreased in females with low or no estradiol replacement. These results indicate that a constant concentration of estradiol at about the mean level present throughout the estrous cycle will result in normal body weight regulation and will maintain sexual behaviors that normally occur only during estrus. These results emphasize that Silastic implants of estradiol do not mimic normal endocrine function since, even at low levels, estradiol implants produce continuous receptivity.

  18. Transfer rates and pattern of PCB isomers and congeners and p,p'-DDE from mother to egg in Adelie penguin (Pygoscelis adeliae)

    SciTech Connect

    Tanabe, S.; Surbramanian, A.; Hidaka, H.; Tatsukawa, R.

    1986-03-01

    Mother to egg transfer of PCB isomers and congeners and p,p'-DDE was examined in Adelie Penguin (Pygoscelis adeliae) from Antarctica. Transfer rate to a clutch of two eggs was estimated to be small, accounting to about 4.0% for both PCBs and p,p-DDE to the burden in mother. No significant difference was found in the concentration ratios of individual PCB isomers and congeners between mother and egg, which apparently differed from those between mother and fetus of striped dolphin previously reported.

  19. Diabetes Prevalence in Relation to Serum Concentrations of Polychlorinated Biphenyl (PCB) Congener Groups and Three Chlorinated Pesticides in a Native American Population

    PubMed Central

    Aminov, Zafar; Haase, Richard; Rej, Robert; Schymura, Maria J.; Santiago-Rivera, Azara; Morse, Gayle; DeCaprio, Anthony; Carpenter, David O.

    2016-01-01

    Background: Exposure to persistent organic pollutants (POPs) is known to increase risk of diabetes. Objective: To determine which POPs are most associated with prevalence of diabetes in 601 Akwesasne Native Americans. Methods: Multiple logistic regression analysis was used to assess associations between quartiles of concentrations of 101 polychlorinated biphenyl (PCBs) congeners, congener groups and three chlorinated pesticides [dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB) and mirex] with diabetes. In Model 1, the relationship between quartiles of exposure and diabetes were adjusted only for sex, age, body mass index (BMI), and total serum lipids. Model 2 included additional adjustment for either total PCBs or total pesticides. Results: Total serum PCB and pesticide concentrations were each significantly associated with prevalence of diabetes when adjusted only for covariates (Model 1), but neither showed a significant OR for highest to lowest quartiles after additional adjustment for the other (Model 2). When applying Model 2 to PCB congener groups and individual pesticides, there were significant omnibus differences between the four quartiles (all ps < 0.042) for most groups, with the exception of penta- and hexachlorobiphenyls, DDE and mirex. However, when comparing highest to lowest quartiles only non- and mono-ortho PCBs [OR = 4.55 (95% CI: 1.48, 13.95)], tri- and tetrachloro PCBs [OR = 3.66 (95% CI: 1.37, –9.78)] and HCB [OR = 2.64 (95% CI: 1.05, 6.61)] showed significant associations with diabetes. Among the non- and mono-ortho congeners, highest to lowest quartile of dioxin TEQs was not significant [OR = 1.82 (95% CI: 0.61, 5.40)] but the OR for the non-dioxin-like congeners was [OR = 5.01 (95% CI: 1.76, 14.24)]. Conclusion: The associations with diabetes after adjustment for other POPs were strongest with the more volatile, non-dioxin-like, low-chlorinated PCB congeners and HCB. Because low-chlorinated congeners are more volatile

  20. Exposure to estradiol before but not during acquisition of LiCl-induced conditioned taste avoidance accelerates extinction.

    PubMed

    Chambers, Kathleen C; Hayes, Unja L

    2002-05-01

    Estradiol accelerates extinction of LiCl-induced conditioned taste avoidance when it is present continuously before and during acquisition. We have suggested that the effect of estradiol on extinction is due to its illness-associated, rather than learning-associated, properties. If this were the case, then one would expect estradiol to act before but not during acquisition. This expectation is based on previous work showing attenuation of learned taste avoidance when rats are given distal preexposure (greater than 24 h before conditioning) or proximal preexposure (less than 24 h before conditioning) to the illness-inducing agent LiCl before acquisition of a LiCl-induced conditioned taste avoidance. In three separate experiments, estradiol was administered during three different time periods via subcutaneous implantation of a 10-mm estradiol-filled capsule. In each experiment, the extinction of estradiol-treated females was compared to that of females implanted with empty capsules. In the first experiment, female rats were given distal exposure to estradiol before acquisition. Capsules were implanted 11 days before acquisition and were removed 2 days before acquisition. In the second experiment, female rats were given proximal exposure to estradiol before acquisition. Capsules were implanted 2.5 h before LiCl was paired with a sucrose solution and were removed 16.5 h later. In the third experiment, female rats were given exposure to estradiol during acquisition. Capsules were implanted at the same time as LiCl administration and were removed 18 h later. The only estradiol-treated females to show accelerated extinction were those given distal preexposure to estradiol in Experiment 1. These data do not support a learning-associated hypothesis and only partially support an illness-associated hypothesis. The failure to find accelerated extinction following proximal preexposure may reflect an inappropriate choice of the parameters used in the experiment or a difference

  1. Estradiol suppression and recovery during leuprolide acetate treatment in women as determined weekly by an ultrasensitive recombinant cell bioassay.

    PubMed

    Larmore, K A; Klein, K O

    2000-12-01

    We studied the time frame of suppression and recovery of estradiol after injection with leuprolide acetate utilizing an ultrasensitive recombinant cell bioassay for estradiol in eight normal premenopausal women. Previous studies have shown suppression of gonadotropins and estradiol at 4 weeks after the depot injection, but no studies have shown the weekly time course of estradiol suppression or recovery. Four women received one 3.75 mg i.m. injection of leuprolide acetate and four received two 3.75 mg doses of leuprolide acetate 4 weeks apart. Estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured weekly for 8 to 12 weeks. Estradiol was significantly suppressed to 26.6 +/- 19.3% of baseline values by week 3 after the initial dose of leuprolide acetate and suppressed to 2.7 +/- 3.1% of baseline values by week 4 (p < 0.01 versus baseline). The actual values were less than 14.7 pmol/l (4 pg/ml) in all women by week 4. Estradiol remained suppressed for 8 weeks after one dose of leuprolide acetate and remained suppressed for 6 weeks after a second dose administered 4 weeks later. LH and FSH followed a similar pattern, but only remained suppressed for 7 weeks after one dose of leuprolide acetate and for 6 weeks after two doses. Estradiol levels at baseline were significantly correlated with body mass index (BMI). We also studied one postmenopausal woman. Her baseline estradiol levels were 10.3 pmol/l (2.8 pg/ml) and were suppressed to 3.9 pmol/l (1.1 pg/ml) by 2 weeks after leuprolide acetate. In conclusion, estradiol was suppressed to postmenopausal levels by the end of the first month of treatment with leuprolide acetate, as determined by an ultrasensitive bioassay. Higher doses would need to be tested to determine whether greater suppression can be achieved. The hypothalamic-pituitary-gonadal axis begins to recover 7 weeks after one dose and 6 weeks after a second dose of leuprolide acetate. This confirms the adequacy of 4-week

  2. Hepatic expression of heme oxygenase-1 and antioxidant response element-mediated genes following administration of ethinyl estradiol to rats

    SciTech Connect

    Morio, Lisa A.; Leone, Angelique; Sawant, Sharmilee P.; Nie, Alex Y.; Brandon Parker, J.; Taggart, Peter; Barron, Alfred M.; McMillian, Michael K. . E-mail: mmcmilli@prdus.jnj.com; Lord, Peter

    2006-11-01

    Heme oxygenase-1 (HO-1) is one of several enzymes induced by hepatotoxicants, and is thought to have an important protective role against cellular stress during liver inflammation and injury. The objective of the present study was to evaluate the role of HO-1 in estradiol-induced liver injury. A single dose of ethinyl estradiol (500 mg/kg, po) resulted in mild liver injury. Repeated administration of ethinyl estradiol (500 mg/kg/day for 4 days, po) resulted in no detectable liver injury or dysfunction. Using RT-PCR analysis, we demonstrate that HO-1 gene expression in whole liver tissue is elevated (> 20-fold) after the single dose of ethinyl estradiol. The number and intensity of HO-1 immunoreactive macrophages were increased after the single dose of ethinyl estradiol. HO-1 expression was undetectable in hepatic parenchymal cells from rats receiving Methocel control or a single dose of ethinyl estradiol, however cytosolic HO-1 immunoreactivity in these cells after repeated dosing of ethinyl estradiol was pronounced. The increases in HO-1 mRNA and HO-1 immunoreactivity following administration of a single dose of ethinyl estradiol suggested that this enzyme might be responsible for the observed protection of the liver during repeated dosing. To investigate the effect of HO-1 expression on ethinyl estradiol-induced hepatotoxicity, rats were pretreated with hemin (50 {mu}mol/kg, ip, a substrate and inducer of HO-1), with tin protoporphyrin IX (60 {mu}mol/kg, ip, an HO-1 inhibitor), or with gadolinium chloride (10 mg/kg, iv, an inhibitor/toxin of Kupffer cells) 24 h before ethinyl estradiol treatment. Pretreatment with modulators of HO-1 expression and activity had generally minimal effects on ethinyl estradiol-induced liver injury. These data suggest that HO-1 plays a limited role in antioxidant defense against ethinyl estradiol-induced oxidative stress and hepatotoxicity, and suggests that other coordinately induced enzymes are responsible for protection observed

  3. Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats.

    PubMed

    Beitnere, Ulrika; Dzirkale, Zane; Isajevs, Sergejs; Rumaks, Juris; Svirskis, Simons; Klusa, Vija

    2014-12-15

    The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) expression by stress. Haloperidol decrease by a third hippocampal BDNF and acetylcholine esterase (but not GAD67) expression, which was normalized by mildronate; it also reversed the haloperidol-induced memory impairment in Barnes test. The results suggest the usefulness of mildronate as protector against neuronal disturbances caused by stress or haloperidol.

  4. Sixteen polymorphic microsatellite markers for a federally threatened species, Hexastylis naniflora (Aristolochiaceae), and co-occurring congeners1

    PubMed Central

    Hamstead, Jacqueline W.; Snider, Brandon L.; Oaks, Robyn; Fitzgerald, Evan; Woodward, Jason; Teat, Alyssa; Hay, Nikolai M.; Estep, Matt C.; Murrell, Zack E.

    2015-01-01

    Premise of the study: Twenty microsatellite loci were developed for the federally threatened species Hexastylis naniflora (Aristolochiaceae) to examine genetic diversity and to distinguish this species from co-occurring congeners, H. heterophylla and H. minor. Methods and Results: Next-generation sequencing approaches were used to identify microsatellite loci and design primers. One hundred fifty-two primer pairs were screened for repeatability, and 20 of these were further characterized for polymorphism. In H. naniflora, the number of alleles identified for polymorphic loci ranged from two to 23 (mean ∼8.8), with a mean heterozygosity of 0.39. Conclusions: These 16 polymorphic primers for H. naniflora will be useful tools in species identification and quantifying genetic diversity within the genus. PMID:26191466

  5. Congenic Strains Confirm the Pleiotropic Effect of Chromosome 4 QTL on Mouse Femoral Geometry and Biomechanical Performance

    PubMed Central

    Kristianto, Jasmin; Litscher, Suzanne J.; Johnson, Michael G.; Patel, Forum; Patel, Mital; Fisher, Jacqueline; Zastrow, Ryley K.; Radcliff, Abigail B.; Blank, Robert D.

    2016-01-01

    A pleiotropic quantitative trait locus (QTL) for bone geometry and mechanical performance in mice was mapped to distal chromosome 4 via an intercross of recombinant congenic mice HcB-8 and HcB-23. To study the QTL in isolation, we have generated C3H.B10-(rs6355453-rs13478087) (C.B.4.3) and C3H.B10-(rs6369860-D4Mit170) (C.B.4.2) congenic strains that harbor ~20 Mb and ~3 Mb, respectively, of chromosome 4 overlapping segments from C57BL/10ScSnA (B10) within the locus on a C3H/DiSnA (C3H) background. Using 3-point bend testing and standard beam equations, we phenotyped these mice for femoral mid-diaphyseal geometry and biomechanical performance. We analyzed the results via 2-way ANOVA, using sex and genotype as factors. In the C.B.4.3 strain, we found that homozygous B10/B10 male mice had smaller cross sectional area (CSA) and reduced total displacement than homozygous C3H/C3H mice. Sex by genotype interaction was also observed for maximum load and stiffness for C3H/C3H and B10/B10 mice, respectively. In C.B.4.2 strain, we found that homozygous B10/B10 mice had lower total displacement, post-yield displacement (PYD), stiffness, yield load and maximum load than mice harboring C3H allele. Sex by genotype interaction was observed in B10/B10 mice for perimeter, outer minor axis (OMA) and CSA. There were no significant differences in tissue level mechanical performance, which suggest that the QTL acts primarily on circumferential bone size. These data confirm the prior QTL mapping data and support other work demonstrating the importance of chromosome 4 QTL on bone modeling and bone responses to mechanical loading. PMID:26849124

  6. (+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist

    SciTech Connect

    Burris, K.D.; Breeding, M.; Sanders-Bush, E. )

    1991-09-01

    Activation of central serotonin 5HT2 receptors is believed to be the primary mechanism whereby lysergic acid diethylamide (LSD) and other hallucinogens induce psychoactive effects. This hypothesis is based on extensive radioligand binding and electrophysiological and behavioral studies in laboratory animals. However, the pharmacological profiles of 5HT2 and 5HT1C receptors are similar, making it difficult to distinguish between effects due to activation of one or the other receptor. For this reason, it was of interest to investigate the interaction of LSD with 5HT1C receptors. Agonist-stimulated phosphoinositide hydrolysis in rat choroid plexus was used as a direct measure of 5HT1C receptor activation. (+)LSD potently stimulated phosphoinositide hydrolysis in intact choroid plexus and in cultures of choroid plexus epithelial cells, with EC50 values of 9 and 26 nM, respectively. The effect of (+)LSD in both systems was blocked by 5HT receptor antagonists with an order of activity consistent with interaction at 5HT1C receptors. Neither (+)-2-bromo-LSD nor lisuride, two nonhallucinogenic congeners of LSD, were able to stimulate 5HT1C receptors in cultured cells or intact choroid plexus. In contrast, lisuride, like (+)LSD, is a partial agonist at 5HT2 receptors in cerebral cortex slices and in NIH 3T3 cells transfected with 5HT2 receptor cDNA. The present finding that (+)LSD, but not its nonhallucinogenic congeners, is a 5HT1C receptor agonist suggests a possible role for these receptors in mediating the psychoactive effects of LSD.

  7. Removal efficiencies for 136 tetra- through octa-chlorinated dibenzo-p-dioxins and dibenzofuran congeners with activated carbons.

    PubMed

    Zhou, Xu-Jian; Li, Xiao-Dong; Ni, Ming-Jiang; Cen, Ke-Fa

    2015-11-01

    In this study, the removal efficiency of 136 tetra- to octa-chlorinated dibenzo-p-dioxin (CDD)/furan (F) congeners from a nitrogen + oxygen carrier gas was studied using a laboratory-scale, fixed bed adsorption system. Two kinds of activated carbon with dissimilar pore structures were used as adsorbents. The total concentration of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) in the source gas was 541 ng/Nm(3) and that of the 17 toxic 2,3,7,8-substituted PCDD/Fs 96.35 ng/Nm(3), accounting for 17.8% of the total original weight amount. Their toxic equivalent quantity (TEQ) was 8.31 ng I-TEQ/Nm(3). For both activated carbons, the removal efficiencies of the ten PCDD/F homologue groups rise with chlorine substitution number. The removal efficiencies vary approximately as a power function of vapor pressure (correlation coefficients r(2) = 0.93 and 0.81, respectively). Competitive adsorption and desorption occur as adsorption time went on, causing elution of the lower chlorinated homologues, i.e. tetra-CDD/F and Penta-CDD/F congeners. In addition, there are significantly different concentration distributions for isomers in the same homologue groups. However, their removal efficiencies have weak correlation with their initial concentrations. The correlation coefficients are from -0.47 to 0.32 and from -0.57 to 0.46 respectively for the two kinds of activated carbons. PMID:26154037

  8. Organochlorine pesticides and polychlorinated biphenyl congeners in wild terrestrial mammals from Croatia: Interspecies comparison of residue levels and compositions.

    PubMed

    Herceg Romanić, Snježana; Klinčić, Darija; Kljaković-Gašpić, Zorana; Kusak, Josip; Reljić, Slaven; Huber, Đuro

    2015-10-01

    In this pilot study, we investigated levels of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in the adipose tissues of two free-ranging terrestrial carnivores from Croatia sampled in 2010 and 2011: the brown bear (Ursus arctos; N=32) and the grey wolf (Canis lupus; N=29). Concentrations of ∑OCPs and ΣPCBs ranged from 0.45 to 4.09 ng g(-1) lipid mass (lm) and from 0.93 to 8.52 ng g(-1) lm in brown bear, and from 1.18 to 5.67 ng g(-1) lm and 2.68 to 48.9 ng g(-1) lm in grey wolf adipose tissues, respectively. PCBs were dominant accounting for over 72% of total analyzed persistent organic pollutants (POPs). The sum of six indicator non-dioxin-like PCBs (Σ6IndNDL PCBs) made up 60-93% and 58-85% of the total congener concentrations in brown bears and wolves, respectively. Although the levels of the measured parameters were significantly higher in grey wolves than in bears, the contaminant profiles of the two species were similar, with γ-HCH, HCB, β-HCH and DDE as major OCP contaminants, and PCB-153>PCB-180≈PCB-170>PCB-138 as the dominant congeners. The sum of hexachlorocyclohexanes (ΣHCHs) and 8 toxicologically relevant dioxin-like PCBs (Σ8ToxDL PCBs) was higher in the males than in the females of the brown bear. Concentrations of ΣDDTs, HCB, ΣOCP, ΣPCBs, Σ6IndNDL PCBs, and toxicologically relevant non-dioxin-like PCBs (ΣToxNDL PCBs) were significantly positively correlated with lipid content in the grey wolf. Concentrations of OCPs and PCBs in brown bears and wolves from Croatia were low and normal for large terrestrial mammals.

  9. BALB/c-congenic ANP32B-deficient mice reveal a modifying locus that determines viability

    PubMed Central

    Leo, Vonny I.; Bunte, Ralph M.; Reilly, Patrick T.

    2015-01-01

    We previously found that deletion of the multifunctional factor ANP32B (a.k.a. SSP29, APRIL, PAL31, PHAPI2) resulted in a severe but strain-specific defect resulting in perinatal lethality. The difficulty in generating an adult cohort of ANP32B-deficient animals limited our ability to examine adult phenotypes, particularly cancer-related phenotypes. We bred the Anp32b-null allele into the BALB/c and FVB/N genetic background. The BALB/c, but not the FVB/N, background provided sufficient frequency of adult Anp32b-null (Anp32b−/−) animals. From these, we found no apparent oncogenic role for this protein in mammary tumorigenesis contrary to what was predicted based on human data. We also found runtism, pathologies in various organ systems, and an unusual clinical chemistry signature in the adult Anp32b−/− mice. Intriguingly, genome-wide single-nucleotide polymorphism analysis suggested that our colony retained an unlinked C57BL/6J locus at high frequency. Breeding this locus to homozygosity demonstrated that it had a strong effect on Anp32b−/− viability indicating that this locus contains a modifier gene of Anp32b with respect to development. This suggests a functionally important genetic interaction with one of a limited number of candidate genes, foremost among them being the variant histone gene H2afv. Using congenic breeding strategies, we have generated a viable ANP32B-deficient animal in a mostly pure background. We have used this animal to reliably exclude mouse ANP32B as an important oncogene in mammary tumorigenesis. Our further phenotyping strengthens the evidence that ANP32B is a widespread regulator of gene expression. These studies may also impact the choice of subsequent groups with respect to congenic breeding versus de novo zygote targeting strategies for background analyses in mouse genetics. PMID:26558540

  10. The SOD1 transgene expressed in erythroid cells alleviates fatal phenotype in congenic NZB/NZW-F1 mice.

    PubMed

    Otsuki, Noriyuki; Konno, Tasuku; Kurahashi, Toshihiro; Suzuki, Saori; Lee, Jaeyong; Okada, Futoshi; Iuchi, Yoshihito; Homma, Takujiro; Fujii, Junichi

    2016-07-01

    Oxidative stress due to a superoxide dismutase 1 (SOD1) deficiency causes anemia and autoimmune responses, which are phenotypically similar to autoimmune hemolytic anemia (AIHA) and systemic lupus erythematosus (SLE) in C57BL/6 mice and aggravates AIHA pathogenesis in New Zealand black (NZB) mice. We report herein on an evaluation of the role of reactive oxygen species (ROS) in a model mouse with inherited SLE, that is, F1 mice of the NZB × New Zealand white (NZW) strain. The ROS levels within red blood cells (RBCs) of the F1 mice were similar to the NZW mice but lower compared to the NZB mice throughout adult period. Regarding SLE pathogenesis, we examined the effects of an SOD1 deficiency or the overexpression of human SOD1 in erythroid cells by establishing corresponding congenic F1 mice. A SOD1 deficiency caused an elevation in ROS production, methemoglobin content, and hyperoxidation of peroxiredoxin in RBC of the F1 mice, which were all consistent with elevated oxidative stress. However, while the overexpression of human SOD1 in erythroid cells extended the life span of the congenic F1 mice, the SOD1 deficiency had no effect on life span compared to wild-type F1 mice. It is generally recognized that NZW mice possess a larval defect in the immune system and that NZB mice trigger an autoimmune reaction in the F1 mice. Our results suggest that the oxidative insult originated from the NZB mouse background has a functional role in triggering an aberrant immune reaction, leading to fatal responses in F1 mice. PMID:27080108

  11. Different Responses of an Invasive Clonal Plant Wedelia trilobata and its Native Congener to Gibberellin: Implications for Biological Invasion.

    PubMed

    Dai, Zhi-Cong; Fu, Wei; Qi, Shan-Shan; Zhai, De-Li; Chen, Si-Chong; Wan, Ling-Yun; Huang, Ping; Du, Dao-Lin

    2016-02-01

    The invasive clonal plant Wedelia trilobata contains higher levels of ent-kaurane diterpenes, which are precursors of gibberellins (GAs), and higher rates of clonal growth than its native congener W. chinensis in invaded habitats. We hypothesized that the higher levels of endogenous GAs facilitate greater ramet growth in W. trilobata compared with W. chinensis. We quantified endogenous levels of GA1+3 in the two species and compared their growth responses to the changes of endogenous and exogenous GA3 by using short-term and long-term hydroponics experiments. After a period of homogeneous cultivation, levels of endogenous GA1+3 were higher in W. trilobata than in W. chinensis. The reduction of endogenous GAs repressed the emergence of adventitious roots and the growth of W. trilobata in the initial cultivation stage, and inhibited its shoot elongation and biomass. Levels of endogenous GA1+3 were positively correlated with the length of shoots and adventitious roots of W. trilobata. Adventitious roots of W. trilobata also emerged earlier and grew faster when treated with exogenous GA3. In contrast, exogenous GA3 treatment inhibited the length of adventitious roots in W. chinensis, and levels of endogenous GA1+3 did not correlate with shoot or adventitious root length. Our study suggests that GAs accelerate the rapid clonal growth of W. trilobata, more than that of its native congener W. chinensis, illustrating the relationship between plant hormones and the clonal growth of invasive plants. These findings are important for understanding the mechanisms associated with the invasiveness of clonal plants and their potential management. PMID:26879680

  12. Strain and sex differences in repeated ethanol treatment-induced motor activity in quasi-congenic mice.

    PubMed

    Sershen, H; Hashim, A; Vadasz, C

    2002-08-01

    The B6.C quasi-congenic Recombinant QTL Introgression (RQI) strains of the b4i5 series have similar genetic background, but differ in about 5% of their genome from the C57BL/6ByJ (B6) background strain because they carry short chromosome segments introgressed from the BALB/cJ (C) donor strain. These RQI strains were derived from mouse lines selectively bred for high activity of mesencephalic tyrosine hydroxylase (TH/MES), therefore genetic variation in dopamine system-related behaviours, such as ethanol-induced motor activity, can be expected. Males and females of 17 RQI and two progenitor strains were tested for initial motor activity for 15 min after a habituating injection of saline, which was followed by an i.p. injection of saline or ethanol (2 g/kg) and an additional test of motor activity for 30 min. This procedure was repeated during 4 subsequent days. In all strains, the first-day ethanol treatment showed an inhibitory effect. With repetition of the treatment the inhibitory effect decreased, and a stimulatory effect could be observed with significant strain- and sex-dependent variation. Females exhibited higher activity in the saline group than males, and reached an equilibrium of inhibition and stimulation sooner than males with repetition of the ethanol treatment. The highest (> 25-fold) difference in activity after repeated ethanol treatment was detected between females of the two strains B6.Cb4i5-Alpha4/Vad and B6.Cb4i5-Beta13/Vad. These results firstly suggest that females are more sensitive to repeated ethanol exposure than males, secondly they support the observations that ethanol has both inhibitory and stimulatory effects on motor activity, which are affected by sex, genotype, and repetition of treatment, and thirdly offer new quasi-congenic animal models with highly different responses to ethanol allowing one to more quickly move to gene detection.

  13. Different Responses of an Invasive Clonal Plant Wedelia trilobata and its Native Congener to Gibberellin: Implications for Biological Invasion.

    PubMed

    Dai, Zhi-Cong; Fu, Wei; Qi, Shan-Shan; Zhai, De-Li; Chen, Si-Chong; Wan, Ling-Yun; Huang, Ping; Du, Dao-Lin

    2016-02-01

    The invasive clonal plant Wedelia trilobata contains higher levels of ent-kaurane diterpenes, which are precursors of gibberellins (GAs), and higher rates of clonal growth than its native congener W. chinensis in invaded habitats. We hypothesized that the higher levels of endogenous GAs facilitate greater ramet growth in W. trilobata compared with W. chinensis. We quantified endogenous levels of GA1+3 in the two species and compared their growth responses to the changes of endogenous and exogenous GA3 by using short-term and long-term hydroponics experiments. After a period of homogeneous cultivation, levels of endogenous GA1+3 were higher in W. trilobata than in W. chinensis. The reduction of endogenous GAs repressed the emergence of adventitious roots and the growth of W. trilobata in the initial cultivation stage, and inhibited its shoot elongation and biomass. Levels of endogenous GA1+3 were positively correlated with the length of shoots and adventitious roots of W. trilobata. Adventitious roots of W. trilobata also emerged earlier and grew faster when treated with exogenous GA3. In contrast, exogenous GA3 treatment inhibited the length of adventitious roots in W. chinensis, and levels of endogenous GA1+3 did not correlate with shoot or adventitious root length. Our study suggests that GAs accelerate the rapid clonal growth of W. trilobata, more than that of its native congener W. chinensis, illustrating the relationship between plant hormones and the clonal growth of invasive plants. These findings are important for understanding the mechanisms associated with the invasiveness of clonal plants and their potential management.

  14. COMPARISON OF THE ESTROGENIC POTENCIES OF ESTRADIOL, ETHYNYLESTRADIOL, DIETHYLSTILBESTROL, NONYLPHENOL AND METHOXYCHLOR IN VIVO AND IN VITRO

    EPA Science Inventory

    Five natural, pharmaceutical, or xenobiotic chemicals (17b-estradiol, ethynylestradiol, diethystilbestrol, nonylphenol, methoxychlor) were tested in two in vitro (MCF-7 breast tumor cell proliferation [E-screen], yeast estrogen system [YES]), and one in vivo (male sheepshead min...

  15. Neuropeptidase activity is down-regulated by estradiol in steroid-sensitive regions of the hypothalamus in female mice.

    PubMed

    Bruce, Lisa A; Cyr, Nicole E; Qiao, Jana W; Defries, Christa C; Tetel, Marc J; Wolfson, Adele J

    2012-08-01

    Thimet oligopeptidase (TOP) and prolyl endopeptidase (PEP) are neuropeptidases involved in the hydrolysis of gonadotropin-releasing hormone, a key component of the hypothalamic-pituitary-gonadal axis. GnRH is regulated in part by feedback from steroid hormones such as estradiol. Previously, we demonstrated that TOP levels are down-regulated by estradiol in reproductively-relevant regions of the female rodent brain. The present study supports these findings by showing that TOP enzyme activity, as well as protein levels, in the ventromedial hypothalamic nucleus of female mice is controlled by estradiol. We further demonstrate that PEP levels in this same brain region are down-regulated by estradiol in parallel with those of TOP. These findings provide evidence that these neuropeptidases are part of the fine control of hormone levels in the HPG axis.

  16. Congener-specific organic carbon-normalized soil and sediment-water partitioning coefficients for the C1 through C8 perfluoroalkyl carboxylic and sulfonic acids.

    PubMed

    Rayne, Sierra; Forest, Kaya

    2009-11-01

    Organic carbon-normalized soil and sediment-water partitioning coefficients (K(oc)) were estimated for all C(1) through C(8) perfluoroalkyl carboxylic (PFCA) and sulfonic (PFSA) acid congeners. The limited experimental K(oc) data set for the straight chain C(7) through C(10) PFCAs and C(8) and C(10) PFSAs was correlated to SPARC and ALOGPS computationally estimated octanol-water partitioning/distribution constants and used to predict K(oc) values for both branched and linear C(1) through C(8) isomers. Branched and linear congeners in this homologue range are generally expected to have K(oc) values > 1, leading to their accumulation in organic matter on sediments and soils, retardation during ground and pore water flow, and the preferential association with dissolved organic matter in aquatic systems. Both increasing perfluoroalkyl chain length and linearity increase K(oc) values with substantial intra- and inter-homologue variation and interhomologue mixing. Variability in K(oc) values among the PFCA and PFSA congeners will likely lead to an enrichment of more linear and longer-chain isomers in organic matter fractions, resulting in aqueous phases fractionated towards shorter-chain branched congeners. The expected magnitude of fractionation will require inclusion in source apportionment models and risk assessments. A comparison of representative established quantitative structure property relationships for estimating K(oc) values from octanol-water partitioning constants suggests that these equilibrium partitioning frameworks may be applicable towards modeling PFCA and PFSA environmental fate processes. PMID:20183495

  17. Tissue Distribution of Polychlorinated Biphenyls and Organochlorine Pesticides and Potential Toxicity to Alaskan Northern Fur Seals Assessed Using PCBs Congener Specific Mode of Action Schemes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concentrations of 145 polychlorinated biphenyl (PCB) congeners were measured using gas chromatography-ion trap mass spectrometry in 8 different tissues (blubber, brain, heart, kidney, liver, lung, muscle, and reproductive tissues) of 10 Alaskan northern fur seals. The mean concentrations of bot...

  18. Fractionation and current time trends of PCB congeners: evolvement of distributions 1950-2010 studied using a global atmosphere-ocean general circulation model

    NASA Astrophysics Data System (ADS)

    Lammel, G.; Stemmler, I.

    2012-05-01

    PCBs are ubiquitous environmental pollutants expected to decline in abiotic environmental media in response to decreasing primary emissions since the 1970s. A coupled atmosphere-ocean general circulation model with embedded dynamic sub-models for atmospheric aerosols and the marine biogeochemistry and air-surface exchange processes with soils, vegetation and the cryosphere is used to study the transport and fate of four PCB congeners covering a range of 3-7 chlorine atoms. The change of the geographic distribution of the PCB mixture reflects the sources and sinks' evolvement over time. Globally, secondary emissions (re-volatilisation from surfaces) are on the long term increasingly gaining importance over primary emissions. They are most important for congeners of medium hydrophobicity (5-6 chlorine atoms). Their levels are predicted to decrease slowest. Congeners' fractionation is characterized both geographically and temporally. It causes enrichment of the lighter, less persistent congeners and more delayed decreasing levels in high latitudes in response to decreasing emissions. Delivery of contaminants to high latitudes is predicted to be more efficient than previously suggested. The results suggest furthermore that the effectiveness of emission control measures may significantly vary among substances: trends of decline in abiotic environmental media do not only vary with latitude (slow in high latitudes), but do also show longitudinal gradients

  19. Coexposure of dioxin-like polychlorinated biphenyls and polychlorinated dibenzo-p-dioxins and dibenzofurans in free-range hens and implications derived from congener profile analysis.

    PubMed

    Lin, Chingju; Hsu, Jing-Fang; Liao, Pao-Chi

    2012-02-29

    The consumption of free-range eggs is becoming more popular worldwide. We analyzed the levels of 12 dioxin-like polychlorinated biphenyls (dl-PCBs) and their congener profiles from 6 free-range and 12 caged egg samples. The mean levels of dl-PCBs in the free-range samples were 5.4 times higher than those in caged eggs. All egg samples exhibited at least two characteristic dl-PCB congener patterns, which reflected distinctive contamination sources. Additionally, for the first time, we demonstrated that the dl-PCB levels in the free-range eggs were highly correlated with elevated levels of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) (r = 0.986; p < 0.001), indicating a coexposure scenario in free-range hens. Cluster analysis of congener patterns implied that this coexposure scenario could be attributed to distinct dl-PCB and PCDD/F sources. This congener profile information provides insights from a different perspective for further identifying potential dl-PCB and PCDD/F sources in the polluted free-range eggs.

  20. USING BASE-SPECIFIC SALMONELLA TESTER STRAINS TO CHARACTERIZE THE TYPES OF MUTATION INDUCED BY BENZIDINE AND BENZIDINE CONGENERS AFTER REDUCTIVE METABOLISM

    EPA Science Inventory

    Abstract
    Benzidine, 4-aminobiphenyl, 3,3'-dichlorobenzidine HCl, 3,3'-dimethylbenzidine, 3,3'- dimethoxybenzidine and benzidine congener-based dye trypan blue were mutagenic in Salmonella typhimurium TAl 00 only with metabolic activation. It was found that a hamster liver 89 ...

  1. Evaluation of Comprehensive 2-D Gas Chromatography-Time-Of-Flight Mass Spectrometry for 209 Chlorinated Biphenyl Congeners in Two Chromatographic Runs

    EPA Science Inventory

    This research evaluates a recently developed comprehensive 2-D GC coupled with a time-of-flight (TOF) mass spectrometer for the potential separation of 209 PCB congeners, using a sequence of 1-D and 2-D chromatographic modes. In two consecutive chromatographic runs, using a 40 m,...

  2. Experimental and theoretical studies into the formation of C4-C6 products in partially chlorinated hydrocarbon pyrolysis systems: a probabilistic approach to congener-specific yield predictions.

    PubMed

    McIntosh, Grant J; Russell, Douglas K

    2014-09-25

    This work presents a study of the pyrolytic formation of vinylacetylene and benzene congeners formed from chlorinated hydrocarbon precursors, a complex, multipath polymerization system formed in a monomer-rich environment. (Co-)pyrolyses of dichloro- and trichloroethylene yield a rich array of products, and assuming a single dominant underlying growth mechanism, this (on comparing expected and observed products) allows a number of potentially competing channels to C4 and C6 products to be ruled out. Poor congener/isomer descriptions rule out even-carbon radical routes, and the absence of C3 and C5 products rule out odd-carbon processes. Vinylidenes appear unable to describe the increased reactivity of acetylenes with chlorination noted in our experiments, leaving molecular acetylene dimerization processes and, in C6 systems, the closely related Diels-Alder cyclization as the likely reaction mechanism. The feasibility of these routes is further supported by ab initio calculations. However, some of the most persuasive evidence is provided by congener-specific yield predictions enabled by the construction of a probability tree analogue of kinetic modeling. This approach is relatively quick to construct, provides surprisingly accurate predictions, and may be a very useful tool in screening for important reaction channels in poorly understood congener- or isomer-rich reaction systems.

  3. Phenomenological and Spectroscopic Analysis on the Effects of Sediment Ageing and Organic Carbon on the Fate of a PCB Congener Spiked to Sediment

    EPA Science Inventory

    This study assesses the full cycle transport and fate of a polychlorinated biphenyl (PCB) congener spiked to sediment to empirically and spectroscopically investigate the effects of sediment ageing and organic carbon on the adsorption, desorption, and reaction of the PCB. Caesar ...

  4. Reproductive Characteristics Differed in a Series of B-Congenic Lines of White Leghorns Evidently Indicating Significant Influence of Major Histocompatibility Complex in Chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reproductive characteristics were compared between a series of seven B-congenic lines of White Leghorns retrospectively using eight year’s reproduction records.The records encompass a total of 33,010 fertile eggs set to hatch under controlled conditions, which were collected accumulatively from 2,1...

  5. A congener-specific PCDD/F emissions inventory for the UK: do current estimates account for the measured atmospheric burden?

    PubMed

    Alcock, R E; Sweetman, A J; Jones, K C

    2001-04-01

    Considerable effort has been expended in the UK and elsewhere to quantify and rank PCDD/F primary sources and emissions to the environment, principally the atmosphere, so that cost-effective source reduction measures can be taken. Here, we predict a congener-specific emissions inventory for primary and secondary nondioxin-regulated sources to the UK atmosphere, estimated to have ranged from 3 to 22 kg in 1996. The inventory profile is dominated by OCDD (approximately 30-40%), 1,2,3,4,6,7,8-HpCDD (approximately 15-19%) and 1,2,3,4,6,7,8-HpCDF (approximately 14-19%). Congeners 2,3,4,7,8-PeCDF and 1,2,3,7,8-PeCDD dominate the sigmaTEQ composition. Mass balance modelling suggests that the predicted congener pattern in UK air (based on the emission inventory) is similar to observed measurements, with absolute concentrations being estimated within a factor of 2 for most congeners. Calculations taking into account atmospheric weathering processes and long range (advective) transport suggest that PCDD/F sources to ambient air are primarily ongoing and that atmospheric mixing will mask individual emission source profiles/identities. This supports measured evidence for the consistency of PCDD/F air profiles observed around the UK throughout the year.

  6. Increased egg estradiol concentration feminizes digit ratios of male pheasants (Phasianus colchicus)

    NASA Astrophysics Data System (ADS)

    Saino, N.; Rubolini, D.; Romano, M.; Boncoraglio, G.

    2007-03-01

    The length ratio between individual digits differs between males and females in humans, other mammals, lizards, and one bird species. Sexual dimorphism in digit ratios and variation among individuals of the same sex may depend on differential exposure to androgens and estrogens during embryonic life. Organizational effects of sex hormones could cause the observed correlations between digit ratios and diverse phenotypic traits in humans. However, no study has investigated experimentally the effect of prenatal estrogens on digit ratios. We analyzed the effect of estradiol injection in ring-necked pheasant (Phasianus colchicus) eggs on digit ratios. Males from control eggs had higher ratios between the second or third and the fourth digit of the right foot compared to females. Estradiol-treated eggs produced males with lower (feminized) right foot second to fourth digit ratio. Thus, we provided the first experimental evidence that prenatal exposure to physiologically high estrogen levels affects bird digit ratios.

  7. Matching plasmon resonances to the C=C and C-H bonds in estradiol

    NASA Astrophysics Data System (ADS)

    Mbomson, Ifeoma G.; McMeekin, Scott; De La Rue, Richard; Johnson, Nigel P.

    2015-03-01

    We tune nanoantennas to resonate within mid-infrared wavelengths to match the vibrational resonances of C=C and C-H of the hormone estradiol. Modelling and fabrication of the nanoantennas produce plasmon resonances between 2 μm to 7 μm. The hormone estradiol was dissolved in ethanol and evaporated, leaving thickness of a few hundreds of nanometres on top of gold asymmetric split H-like shaped on a fused silica substrate. The reflectance was measured and a red-shift is recorded from the resonators plasmonic peaks. Fourier transform infrared spectroscopy is use to observe enhanced spectra of the stretching modes for the analyte which belongs to alkenyl biochemical group.

  8. Effects of ionizing irradiation on the estradiol and progesterone receptors in rat mammary tumors

    SciTech Connect

    Janssens, J.P.; Wittevrongel, C.; Van Dam, J.; Goddeeris, P.; Lauwerijns, J.M.; De Loecker, W.

    1981-02-01

    The determination of estradiol and progesterone receptor concentrations in mammary tumors is useful in predicting the hormone responsiveness. As this assay is carried out on tumor tissue which may have been subjected to radiotherapy, the possibility of an ionizing irradiation affecting the steroid receptor levels in neoplastic tissue should be taken into account. The steroid receptor concentrations are examined in dimethylbenz(a)anthracene-induced tumors os Sprague-Dawley rats. The estradiol and the progesterone receptor titers become reduced significantly after treatment with 20 Gray while an application with 7 Gray does not affect the titer values. After treatment of the tumor with 20 Gray, the steroid receptor concentrations decrease progressively, reaching a maximal reduction 20 to 30 days after exposure. As radiation treatment affects the receptor concentrations, this should be kept in mind when interpreting the steroid receptor concentrations.

  9. Modulatory role of 17β-estradiol in the tumor microenvironment of thyroid cancer.

    PubMed

    Hima, Sithul; Sreeja, Sreeharshan

    2016-02-01

    Thyroid cancer (TC) is an endocrine related cancer and is well coupled with the female reproductive hormone, 17β-estradiol (estrogen). Plenty of articles have discussed the role of tumor microenvironment (TME) with different types of tumors in a broad-spectrum but the role of female reproductive hormone, that is, involvement of estrogen in TME of TC have not been reviewed elsewhere. The aim of this review is to analyze how 17β-estradiol affects the TME of TC and also that subsequently leads to progression of cancer. This review is given a new insight on: 1) the estrogen's involvement in TME of TC; 2) how it interferes with the complex cross talk of signaling pathways established between cancer cells, host cells, and their surrounding extracellular matrix; and 3) the important factors of microenvironment comprising inflammation, hypoxia, angiogenesis, metastasis, various growth factors and fibroblasts in stromal cells. PMID:26707588

  10. Gene expression responses of European flounder (Platichthys flesus) to 17-beta estradiol.

    PubMed

    Williams, Tim D; Diab, Amer M; George, Stephen G; Sabine, Victoria; Chipman, James K

    2007-02-01

    Male European flounder (Platichthys flesus) were intraperitoneally injected with 10mg/kg 17-beta estradiol and tissues taken from individuals over a timecourse of 16 days. The GENIPOL P. flesus cDNA microarray was employed to detect hepatic gene expression differences between fish treated with estradiol and saline controls. Known biomarkers of estrogen exposure, choriogenin L and vitellogenins, showed sustained induction over the time-course. Among 175 identified clones showing sustained statistically significant induction or repression, those associated with the Gene Ontology terms mitochondria, amino acid synthesis, ubiquitination and apoptosis were included amongst those induced while those associated with immune function, electron transport, cell signalling and protein phosphorylation were repressed. Thus, we show the gene expression response of an environmentally relevant fish species to a high dose of an estrogenic endocrine disruptor and also report the sequencing of a further 2121 flounder ESTs.

  11. Randomized Controlled Trial of Low-Dose Estradiol and the SNRI Venlafaxine for Vasomotor Symptoms

    PubMed Central

    Joffe, Hadine; Guthrie, Katherine A.; LaCroix, Andrea Z.; Reed, Susan D.; Ensrud, Kristine E.; Manson, JoAnn E.; Newton, Katherine M.; Freeman, Ellen W.; Anderson, Garnet L.; Larson, Joseph C.; Hunt, Julie; Shifren, Jan; Rexrode, Kathryn M.; Caan, Bette; Sternfeld, Barbara; Carpenter, Janet S.; Cohen, Lee

    2014-01-01

    Importance Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine is used widely as a non-hormonal treatment. While clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen, these medications have not been simultaneously evaluated in one clinical trial. Objective To determine the efficacy and tolerability of low-dose oral 17-beta-estradiol and low-dose venlafaxine XR in alleviating vasomotor symptoms. Design and Participants 339 peri- and postmenopausal women with ≥2 bothersome vasomotor symptoms per day (mean 8.1, SD 5.3/day) were recruited from the community to MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) clinical network sites November 2011—October 2012. Interventions Participants were randomized to double-blinded treatment with low-dose oral 17-beta-estradiol 0.5-mg/day (n=97), low-dose venlafaxine XR 75-mg/day (n=96), or placebo (n=146) for 8 weeks. Main Outcomes Primary outcome was the mean daily frequency of vasomotor symptoms after 8 weeks of treatment. Secondary outcomes were vasomotor symptom severity, bother and interference. Intent-to-treat analyses compared change in vasomotor symptom frequency between each active intervention and placebo and between the two active treatments. Results Compared to baseline, mean vasomotor symptom frequency at week 8 decreased by 53% with estradiol, 48% with venlafaxine, and 29% with placebo. Estradiol reduced the frequency of symptoms by 2.3 (95% CI 1.3–3.4) more per day than placebo (p<0.001), and venlafaxine by 1.8 (95% CI 0.8–2.7) more per day than placebo (p=0.005). Results were consistent for VMS severity, bother and interference. Low-dose estradiol reduced symptom frequency by 0.6 more per day than venlafaxine (95% CI, 1.8 more per day to 0.6 fewer per day than

  12. Simultaneous Degradation of Estrone, 17β-Estradiol and 17α-Ethinyl Estradiol in an Aqueous UV/H2O2 System

    PubMed Central

    Ma, Xiaoyan; Zhang, Chao; Deng, Jing; Song, Yali; Li, Qingsong; Guo, Yaping; Li, Cong

    2015-01-01

    UV/H2O2, which is an advanced treatment technology used to reduce multiple contaminants, is effective in potable water treatment. Simultaneous degradation effects and kinetics of three types of coexisting micropollutant estrogens (steroid estrogens, SEs), including estrone (E1), 17β-estradiol (E2) and 17α-ethinyl estradiol (EE2), in deionized water were studied. Experiments were carried out with ultraviolet-C (UVC) radiation, together with hydrogen peroxide (H2O2), in a cylinder photoreactor. The results demonstrated that the degradation processes of all of the estrogens strongly fit first-order kinetics. Single solutions of E1, E2 and EE2 showed higher degradation rates and removal efficiencies under the same reaction conditions compared with those under mixed conditions. Coexisting combinations of estrogens were put into the UV/H2O2 system to estimate their possible competitive influences on each other by examining their removal efficiencies and reaction rate constant, k, values. E1 is predominantly reduced rapidly during the competition, while the presence of other estrogens has negligible impacts on E1; however, the degradation of E2 and EE2 is affected by the competitive background, not in relation to the types but to the existing amounts. In the UV/H2O2 system, photocatalysis of the estrogens can stably produce an intermediate X, with the highest quantity coming from E1, while considerably lower quantities are obtained from E2 and EE2. PMID:26404330

  13. Effects of oral exposure to naturally-occurring and synthetic deoxynivalenol congeners on proinflammatory cytokine and chemokine mRNA expression in the mouse

    SciTech Connect

    Wu, Wenda; He, Kaiyu; Zhou, Hui-Ren; Berthiller, Franz; Adam, Gerhard; Sugita-Konishi, Yoshiko; Watanabe, Maiko; Krantis, Anthony; Durst, Tony; Zhang, Haibin; Pestka, James J.

    2014-07-15

    The foodborne mycotoxin deoxynivalenol (DON) induces a ribotoxic stress response in mononuclear phagocytes that mediate aberrant multi-organ upregulation of TNF-α, interleukins and chemokines in experimental animals. While other DON congeners also exist as food contaminants or pharmacologically-active derivatives, it is not known how these compounds affect expression of these cytokine genes in vivo. To address this gap, we compared in mice the acute effects of oral DON exposure to that of seven relevant congeners on splenic expression of representative cytokine mRNAs after 2 and 6 h. Congeners included the 8-ketotrichothecenes 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), nivalenol (NIV), the plant metabolite DON-3-glucoside (D3G) and two synthetic DON derivatives with novel satiety-inducing properties (EN139528 and EN139544). DON markedly induced transient upregulation of TNF-α IL-1β, IL-6, CXCL-2, CCL-2 and CCL-7 mRNA expressions. The two ADONs also evoked mRNA expression of these genes but to a relatively lesser extent. FX induced more persistent responses than the other DON congeners and, compared to DON, was: 1) more potent in inducing IL-1β mRNA, 2) approximately equipotent in the induction of TNF-α and CCL-2 mRNAs, and 3) less potent at upregulating IL-6, CXCL-2, and CCL-2 mRNAs. EN139528's effects were similar to NIV, the least potent 8-ketotrichothecene, while D3G and EN139544 were largely incapable of eliciting cytokine or chemokine mRNA responses. Taken together, the results presented herein provide important new insights into the potential of naturally-occurring and synthetic DON congeners to elicit aberrant mRNA upregulation of cytokines associated with acute and chronic trichothecene toxicity. - Highlights: • We compared effects of DON congeners on biomarker proinflammatory genes in mice. • Oral DON induced splenic IL-1β, IL-6, TNF-α,CXCL-2, CCL-2 and CCL-7 mRNAs. • 8-Ketotrichothecene ranking for

  14. Polybrominated diphenyl ether congeners in the young-of-the-year bluefish, Pomatomus saltatrix, from several nursery habitats along the US Atlantic coastline.

    PubMed

    Deshpande, Ashok D; Dockum, Bruce W

    2013-12-15

    Spatial trends of polybrominated diphenyl ether (PBDE) congeners were examined by using high resolution gas chromatography-low resolution electron impact mass spectrometry (GC-EIMS) in 414 samples of young-of-the-year (YOY) bluefish (Pomatomus saltatrix) collected from a total of 29 nursery habitats along the US Atlantic coastline from Massachusetts to Florida. Of the 26 target PBDE congeners, BDE-47 (4 Br), BDE-100 (5 Br), BDE-49 (4 Br), BDE-99 (5 Br), and BDE-154 (6 Br) were the five most frequently detected congeners in the order of decreasing importance. The sum of the concentrations of five major PBDE congeners, referred to as ΣPBDEs, varied between estuaries and also among samples from a given estuary. ΣPBDEs were lowest in YOY bluefish from Vineyard Sound, Nantucket Sound, Great Bay, Delaware Bay, Lynnhaven Bay, Cape Lookout, and Crescent Beach, with maximum ΣPBDE concentrations below 10 ng/g wet weight. ΣPBDEs in three bluefish samples from Stamford Harbor were detected at relatively high to unusually high concentrations of 69.1, 205, and 561 ng/g wet weight. ΣPBDE values for other Stamford Harbor bluefish were generally low. Highest PBDE concentrations were detected in the vicinity of industrial and urban locations within the New York-New Jersey metropolitan complex. Among them, bluefish from Newark Bay were generally the most contaminated with an average ΣPBDE value of 56.6 ± 30.8 ng/g wet weight. ΣPBDEs in bluefish from Newark Bay were numerically greater than ΣPBDEs in bluefish from all locations, however these differences were not statistically significant. Modest to good correlations between ΣPBDEs and lipids were observed for YOY bluefish from Buzzards Bay, Upper New Bedford Harbor, Lower New Bedford Harbor, Outer New Bedford Harbor, Providence Harbor, Housatonic River, Norwalk Harbor, Little Neck Bay, Newark Bay, Sandy Hook Bay, Great Bay, Delaware Bay, Patuxent River and Crescent Beach. Poor correlations between ΣPBDE and lipids were

  15. Estradiol accelerates extinction of lithium chloride-induced conditioned taste aversions through its illness-associated properties.

    PubMed

    Yuan, D L; Chambers, K C

    1999-12-01

    Estradiol accelerates extinction of LiCl-induced conditioned taste aversions when it is present during a period that starts 2-3 days after acquisition and extends throughout extinction (before and during extinction). It has been suggested that estradiol acts before, not during, extinction and that its effect on extinction is associated with its illness-inducing properties. This hypothesis is based on previous work which shows an attenuation of conditioned taste aversion learning when rats are exposed to illness-inducing agents during a period that starts 2 days after acquisition and ends 2 days before extinction trials are initiated. Four experiments were designed to test elements of this hypothesis. The first two experiments demonstrated that if an estradiol-filled Silastic capsule is implanted before extinction of a LiCl-induced aversion, when the conditioned taste is not present, it accelerates extinction, but if it is implanted during extinction, when the conditioned taste is present, it prolongs extinction. The third experiment showed that the same dose of estradiol that accelerates extinction of a LiCl-induced aversion was effective in producing a conditioned taste aversion when it was present for 18 h after consumption of a novel sucrose solution. The fourth experiment indicated that serum levels of estradiol were elevated during the 18 h. These results are consistent with the hypothesis that the acceleration of extinction by estradiol is associated with its illness-inducing properties. It is suggested that estradiol acts on neural areas that mediate illness information and that one of these areas, the area postrema is necessary for estradiol to accelerate extinction of a LiCl-induced aversion.

  16. Polychlorinated biphenyl concentrations, congener profiles, and ratios in the fat tissue, eggs, and plasma of snapping turtles (Chelydra s. serpentina) from the Ohio Basin of Lake Erie, USA.

    PubMed

    Dabrowska, H; Fisher, S W; Estenik, J; Kidekhel, R; Stromberg, P

    2006-08-01

    Concentrations and profiles of polychlorinated biphenyls (PCBs) were determined in three tissues of adult snapping turtles (Chelydra serpentina serpentina) from six locations in the Ohio Basin of Lake Erie to characterize tissue variation and geographic trends. The locations included the Ohio Areas of Concern, i.e., the Ashtabula, Black, and Maumee Rivers; the Ottawa River near Toledo; and two reference sites. Mean total PCBs were greatest in turtles from the Ottawa River followed by the Maumee, Ashtabula, and Black Rivers. All three types of samples-fat tissue (FT), eggs, and plasma-showed the same geographic trend in PCB levels. On a wet-weight basis, mean concentrations ranged from 2,148 to 18,669 ng/g in FT, from 183 to 3,683 ng/g in eggs, and from 18 to 201 ng/g in plasma. Across all sites, total PCB concentrations between the tissues were significantly correlated (0.001 < p < 0.005; Pearson correlation coefficient (r ( P )) was between 0.720 and 0.954). Two distinctly different profiles with respect to relative congener and homologue concentrations were found among the sites. One that included four of the six sites examined was characterized by hexa-chlorobiphenyl (hexa-CB) dominance followed by hepta-CBs, with PCBs no. 138 + 163, 153 + 132 + 105, and 180 being the most abundant congeners. The second profile, specific for turtles from the Ottawa River, was different from the first in that tetra-CBs were the most abundant congeners followed by hexa-CBs. Analysis of variance (ANOVA) indicated significant intertissue differences in the PCB homologue profiles, i.e., FT had a higher percentage of hepta-, octa-, and nona-CBs compared with eggs and plasma, whereas eggs showed a higher percentage of hexa-CBs. At any listed location, FT, eggs, and plasma had the same congener profile. An intertissue distribution of lipid-normalized individual congener concentrations examined by regression analyses revealed significant egg-FT, egg-plasma, and FT-plasma relations for

  17. Testosterone and Progesterone, But Not Estradiol, Stimulate Muscle Protein Synthesis in Postmenopausal Women

    PubMed Central

    Smith, Gordon I.; Yoshino, Jun; Reeds, Dominic N.; Bradley, David; Burrows, Rachel E.; Heisey, Henry D.; Moseley, Anna C.

    2014-01-01

    Context: The effect of the female sex steroids, estradiol and progesterone, on muscle protein turnover is unclear. Therefore, it is unknown whether the changes in the hormonal milieu throughout the life span in women contribute to the changes in muscle protein turnover and muscle mass (eg, age associated muscle loss). Objective: The objective of this study was to provide a comprehensive evaluation of the effect of sex hormones on muscle protein synthesis and gene expression of growth-regulatory factors [ie, myogenic differentiation 1 (MYOD1), myostatin (MSTN), follistatin (FST), and forkhead box O3 (FOXO3)]. Subjects and Design: We measured the basal rate of muscle protein synthesis and the expression of muscle growth-regulatory genes in 12 premenopausal women and four groups of postmenopausal women (n = 24 total) who were studied before and after treatment with T, estradiol, or progesterone or no intervention (control group). All women were healthy, and pre- and postmenopausal women were carefully matched on body mass, body composition, and insulin sensitivity. Results: The muscle protein fractional synthesis rate was approximately 20% faster, and MYOD1, FST, and FOXO3 mRNA expressions were approximately 40%–90% greater (all P < .05) in postmenopausal than premenopausal women. In postmenopausal women, both T and progesterone treatment increased the muscle protein fractional synthesis rate by approximately 50% (both P < .01), whereas it was not affected by estradiol treatment and was unchanged in the control group. Progesterone treatment increased MYOD1 mRNA expression (P < .05) but had no effect on MSTN, FST, and FOXO3 mRNA expression. T and estradiol treatment had no effect on skeletal muscle MYOD1, MSTN, FST, and FOXO3 mRNA expression. Conclusion: Muscle protein turnover is faster in older, postmenopausal women compared with younger, premenopausal women, but these age-related differences do not appear to be explained by the age- and menopause-related changes

  18. Estradiol and brain serotonin reuptake transporter in long-term ovariectomized parkinsonian monkeys.

    PubMed

    Sánchez, Maria Gabriela; Morissette, Marc; Di Paolo, Thérèse

    2013-08-01

    This study evaluated the effect of a one month 17β-estradiol treatment on brain serotonin (5-HT) reuptake transporter (SERT) in long-term ovariectomized (OVX) female monkeys (Macaca fascicularis) bearing a unilateral lesion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injected directly into the left substantia nigra modeling Parkinson disease (PD). Ovariectomy and MPTP lesion were performed four years before the estrogen treatment to model postmenopausal PD patients. SERT was measured by autoradiography using the radioligand [(3)H]Citalopram. Specific binding to SERT decreased in anterior cerebral cortex, nucleus accumbens, caudate nucleus and putamen on the lesioned side of 17β-estradiol and vehicle-treated monkeys compared to the intact side. In caudate nucleus and putamen the lesioned-induced decrease of [(3)H]Citalopram specific binding was more extensive in anterior and middle than posterior parts. [(3)H]Citalopram specific binding was increased in the cortex anterior cingulate gyrus of monkeys treated with 17β-estradiol in both brain hemispheres and was unchanged in the other brain regions investigated including the raphe nucleus. Positive correlations between [(3)H]Citalopram specific binding and 5-HT as well as 5-HIAA concentrations (reported previously) were obtained in the caudate nucleus and putamen and a negative correlation between SERT binding and 5-HIAA/5-HT concentration ratio suggesting MPTP lesion-induced 5-HT neuronal loss and lower 5-HT neurotransmission controlling and decreasing SERT for homeostasis. 17β-estradiol treatment initiated four years after ovariectomy of monkeys modeling hormonal conditions of post-menopause shows that SERT still displays some responsiveness to estrogens as observed in the anterior cingulate cortex. These results support a role of estrogens in 5-HT activity in PD. PMID:23719069

  19. Modulation of ovine fetal adrenocorticotropin secretion by androstenedione and 17beta-estradiol.

    PubMed

    Saoud, C J; Wood, C E

    1997-04-01

    Parturition in sheep is initiated by increases in activity of the fetal hypothalamic-pituitary-adrenal axis. We have previously reported that cortisol negative feedback efficacy is decreased at the end of gestation. The present study was designed to test the hypothesis that increasing plasma estrogen and/or androgen concentrations in the fetus might increase plasma adrenocorticotropic hormone (ACTH) concentration, either by stimulating ACTH secretion or by altering the negative feedback effect of cortisol on ACTH. Fetal sheep were chronically catheterized and treated with no steroid (control), 17beta-estradiol, or androstenedione (each approximately 0.24 mg/day). After catheterization and implantation of steroid pellet, fetuses were subjected to two short (10 min) periods of sodium nitroprusside-induced hypotension with or without pretreatment with intravenous infusion of hydrocortisone sodium succinate (0.5 microg/min) to test fetal ACTH responsiveness to stress and cortisol negative feedback efficacy. Estradiol treatment significantly increased basal plasma ACTH and cortisol concentrations relative to control fetuses but did not interfere with the inhibition of ACTH secretion by cortisol. Fetal plasma ACTH responses to hypotension were significantly suppressed approximately 60% in both control and estradiol-treated groups. Androstenedione treatment significantly increased basal fetal plasma ACTH and decreased basal fetal plasma cortisol concentration. Androstenedione did not alter stimulated levels of fetal ACTH but did block the inhibition of stimulated ACTH by cortisol. We conclude that increased fetal cortisol and ACTH secretion at the end of gestation may be due to the combined effects of the gonadal steroids in that estradiol increases basal plasma ACTH secretion while androstenedione reduces cortisol negative feedback efficacy.

  20. Non-invasive methods for estradiol recovery from infant fecal samples.

    PubMed

    Thompson, Amanda L; Whitten, Patricia L; Johnson, Michael L; Lampl, Michelle

    2010-01-01

    While the activation of the infant hypothalamic-pituitary-gonadal axis and the existence of a postnatal gonadotropin surge were first documented in the early 1970s, study of the longitudinal development of gonadal hormones in infancy, and the potential physiological and behavioral correlates of this development, have been hampered by reliance on infrequent serum sampling. The present study reports the validation of a non-invasive method for repeated assessment of steroid hormones in infant fecal samples. Fecal samples were collected in and excised from cotton diaper liners and extracted using methanol. Extracts were analyzed for estradiol using a diluted assay modification. Method validity was supported by a steroid recovery rate of at least 80%, a sensitivity of 0.35 pg/ml, and inter- and intra-assay coefficients of variations of less than 10 and 20%, respectively. Variation in estradiol concentration was assessed across (1) sample type (scraped vs. cut from diaper liner), (2) time of day (morning vs. afternoon/evening samples), (3) time interval between samples, and (4) time-to-assay (1 day vs. 489 days after collection). Of these characteristics, only the time interval between samples within an individual was significantly associated with estradiol concentration. This is the first report of human infant fecal estradiol levels. The results support fecal recovery as a novel and powerful non-invasive tool for longitudinal studies of human infants, expanding research opportunities for investigating development of sex-specific behaviors in infancy, and the potential effects of endocrine disruptors on development.

  1. Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.

    PubMed

    Al Abed, Alice Shaam; Sellami, Azza; Brayda-Bruno, Laurent; Lamothe, Valérie; Noguès, Xavier; Potier, Mylène; Bennetau-Pelissero, Catherine; Marighetto, Aline

    2016-07-01

    Because estrogens have mostly been studied in gonadectomized females, effects of chronic exposure to environmental estrogens in the general population are underestimated. Estrogens can enhance hippocampus-dependent memory through the modulation of information storage. However, declarative memory, the hippocampus-dependent memory of facts and events, demands more than abilities to retain information. Specifically, memory of repetitive events of everyday life such as "where I parked" requires abilities to organize/update memories to prevent proactive interference from similar memories of previous "parking events". Whether such organizational processes are estrogen-sensitive is unknown. We here studied, in intact young and aged adult mice, drinking-water (1μM) estradiol effects on both retention and organizational components of hippocampus-dependent memory, using a radial-maze task of everyday-like memory. Demand on retention vs organization was manipulated by varying the time-interval separating repetitions of similar events. Estradiol increased performance in young and aged mice under minimized organizational demand, but failed to improve the age-associated memory impairment and diminished performance in young mice under high organizational demand. In fact, estradiol prolonged mnemonic retention of successive events without improving organization abilities, hence resulted in more proactive interference from irrelevant memories. c-Fos imaging of testing-induced brain activations showed that the deterioration of young memory was associated with dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our findings support the view that estradiol is promnesic but also reveal that such property can paradoxically impair memory. These findings have important outcomes regarding health issues relative to the impact of environmental estrogens in the general population.

  2. Association Between Serum Levels of Testosterone and Estradiol With Meibomian Gland Assessments in Postmenopausal Women

    PubMed Central

    Ablamowicz, Anna F.; Nichols, Jason J.; Nichols, Kelly K.

    2016-01-01

    Purpose The aims of this analysis were to determine if there is an association between serum levels of testosterone and estradiol with meibomian gland (MG) morphology and lipid layer thickness. Methods The data used for this analysis were collected from postmenopausal women with and without dry eye disease. Meibography was used to assess MG dropout on the central two-thirds of the eyelid and biomicroscopy was used for assessing MG expressibility and meibum quality. Venous blood samples were drawn for serum hormone level analysis. The Kruskal-Wallis test and Spearman correlations were used for statistical analysis. Results One hundred ninety-eight postmenopausal women with an average age of 61.2 (±9.1) years were included in this analysis. Testosterone levels showed significant differences between MG dropout grades 1 and 4 (P = 0.002) and grades 2 and 4 (P = 0.01), whereas estradiol levels were different based on MG dropout (P = 0.53). No significant correlations were found between testosterone (r = 0.10, P = 0.17) or estradiol (r = 0.05, P = 0.45) and lipid layer thickness. Conclusions Testosterone levels were increased with MG dropout, which was significant between the mild and severe dropout groups, whereas no significant differences were found with estradiol and any MG assessment. Although the literature suggests an association of serum hormone levels and pathogenesis of dry eye disease in postmenopausal women, analysis of active sex steroid precursors and local tissue hormone levels may prove more useful. PMID:26830366

  3. Estradiol-induced hypophagia is associated with the differential mRNA expression of hypothalamic neuropeptides.

    PubMed

    Silva, L E C M; Castro, M; Amaral, F C; Antunes-Rodrigues, J; Elias, L L K

    2010-08-01

    Estradiol participates in the control of energy homeostasis, as demonstrated by an increase in food intake and in body weight gain after ovariectomy in rats. In the present study, female Wistar rats (200-230 g, N = 5-15 per group), with free access to chow, were individually housed in metabolic cages. We investigated food intake, body weight, plasma leptin levels, measured by specific radioimmunoassay, and the hypothalamic mRNA expression of orexigenic and anorexigenic neuropeptides, determined by real-time PCR, in ovariectomized rats with (OVX+E) and without (OVX) estradiol cypionate treatment (10 microg/kg body weight, sc, for 8 days). Hormonal and mRNA expression were determined at pre-feeding and 4 h after food intake. OVX+E rats showed lower food intake, less body weight gain and lower plasma leptin levels. In the OVX+E group, we also observed a reduction of neuropeptide Y (NPY), agouti-related protein (AgRP) and cocaine- and amphetamine-regulated transcript (CART) mRNA expression in the arcuate nucleus and a decrease in orexin A in the lateral hypothalamic area (LHA). There was an increase in leptin receptor (LepRb), melanocortin-4 receptor (MC4-R), CART, and mainly corticotropin-releasing hormone (CRH) mRNA in the paraventricular nucleus and LepRb and CART mRNA in the LHA. These data show that hypophagia induced by estradiol treatment is associated with reduced hypothalamic expression of orexigenic peptides such as NPY, AgRP and orexin A, and increased expression of the anorexigenic mediators MC4-R, LepRb and CRH. In conclusion, estradiol decreases food intake, and this effect seems to be mediated by peripheral factors such as leptin and the differential mRNA expression of neuropeptides in the hypothalamus.

  4. 17β-estradiol differentially regulates stress circuitry activity in healthy and depressed women.

    PubMed

    Jacobs, Emily G; Holsen, Laura M; Lancaster, Katie; Makris, Nikos; Whitfield-Gabrieli, Sue; Remington, Anne; Weiss, Blair; Buka, Stephen; Klibanski, Anne; Goldstein, Jill M

    2015-02-01

    Many regions within stress neurocircuitry, including the anterior hypothalamus, amygdala, hippocampus, and medial prefrontal cortex, are densely populated with sex steroid receptors. Substantial evidence from animal studies indicates that the gonadal hormone 17β-estradiol (E₂) impacts the structure and function of these regions, but human studies are limited. Characterizing estradiol's role in stress circuitry in vivo in humans may have important clinical implications given the comorbidity between major depressive disorder (MDD), stress circuitry dysfunction and endocrine dysregulation. In this study, we determined estradiol's role in modulating activity within cortical and subcortical stress circuitry regions in healthy and MDD women. Subjects were part of a population-based birth cohort, the New England Family Study. Capitalizing on the endogenous fluctuation in E₂ during the menstrual cycle, we conducted a within-person repeated-measures functional neuroimaging study in which 15 women with recurrent MDD, in remission, and 15 healthy control women underwent hormonal evaluations, behavioral testing, and fMRI scanning on two occasions, under low and high E₂ conditions. Subjects completed an fMRI scan while undergoing a mild visual stress challenge that reliably activated stress neural circuitry. Results demonstrate that E₂ modulates activity across key stress circuitry regions, including bilateral amygdala, hippocampus, and hypothalamus. In healthy women, robust task-evoked BOLD signal changes observed under low E₂ conditions were attenuated under high E₂ conditions. This hormonal capacity to regulate activity in stress circuitry was not observed in MDD women, despite their remitted status, suggesting that dysregulation of gonadal hormone function may be a characteristic trait of the disease. These findings serve to deepen our understanding of estradiol's actions in the healthy brain and the neurobiological mechanisms that may underlie the pronounced

  5. Effects of estradiol on cocaine self-administration and cocaine discrimination by female rhesus monkeys.

    PubMed

    Mello, Nancy K; Negus, S Stevens; Knudson, Inge M; Kelly, Maureen; Mendelson, Jack H

    2008-03-01

    The ovarian steroid hormone, estradiol, enhances the reinforcing and locomotor activating effects of cocaine in rodents under some conditions. The present study evaluated the acute effects of estradiol benzoate (E(2)beta) on cocaine self-administration and cocaine discrimination in female rhesus monkeys. Cocaine self-administration (0.10 mg/kg/inj., i.v.) was maintained on a fixed-ratio (FR) 30 schedule of reinforcement, and monkeys had access to cocaine during one 2-h session each day. E(2)beta in a cyclodextrin vehicle (0.00001-0.01 mg/kg, i.m.) was administered 30 min before test sessions conducted twice each week. Cocaine doses were administered in an irregular order during each dose-effect curve determination (0.001-0.3 mg/kg/inj.). Blood samples were collected after test sessions to determine 17beta-estradiol levels. Banana-flavored food pellets were available on an FR 30 schedule in three 1-h sessions each day. Five monkeys were trained to discriminate cocaine (0.18 mg/kg, i.m.) from saline in a two-key food-reinforced procedure, and the effects of pretreatment with E(2)beta in cyclodextrin and in sesame oil were studied. Acute administration of E(2)beta did not consistently alter the cocaine self-administration or drug discrimination dose-effect curves in comparison to saline control treatment. Females also did not self-administer E(2)beta (0.00001-0.10 mg/kg, i.v.) above saline levels. Finally, E(2)beta (0.0001-0.01 mg/kg, i.m.) did not substitute for cocaine in monkeys trained to discriminate cocaine from saline. Taken together, these data suggest that over the dose range studied, estradiol administration does not consistently alter the abuse-related effects of cocaine in female rhesus monkeys. PMID:17507915

  6. Cognitive Functions, Concentration of Endogenous Estradiol, Estrogen Receptor α (ERα) Polymorphism in Postmenopausal Women

    PubMed Central

    Bojar, Iwona; Pinkas, Jarosław; Wierzbińska-Stępniak, Anna; Raczkiewicz, Dorota; Owoc, Alfred; Gujski, Mariusz

    2016-01-01

    Background The goal of this study was to investigate the relationship between cognitive functions and the level of endogenous estradiol in postmenopausal women, according to which estrogen receptor α (ERα) polymorphism the woman carries. Material/Methods The study group consisted of 210 women. The inclusion criteria were: minimum 2 years after the last menstruation, FSH concentration 30 U/ml, and no dementia signs on Montreal Cognitive Assessment (MoCA). A computerized battery of Central Nervous System Vital Signs (CNS VS) test was used to diagnose cognitive functions. Genotyping of the ERα polymorphism was performed using a polymerase chain reaction and restriction enzymes (PCR-RFLP). Blood plasma was tested for FSH and estradiol (E2). Statistical analysis was performed using STATISTICA software. Results A relationship was confirmed between standard scores for 3 cognitive functions: general memory, verbal memory, and processing speed, and the XbaI polymorphism in the women in the study. In the group of women with genotype TT PvuII, significant positive relationships were observed between the concentration of E2 and the standard scores of 3 cognitive functions: general memory, verbal memory, and processing speed. In the group of women with genotype TC PvuII, significant negative correlations were found between the concentration of E2 and the standard scores of 4 cognitive functions: NCI, general memory, verbal memory, and processing speed. Conclusions ERα polymorphism exerted an effect on the interaction between the concentration of estradiol and the results for cognitive functions. The concentration of estradiol did not depend on Xba1 and PvuII polymorphisms. The results for cognitive functions depended on which Xba1 polymorphism the woman carried. PMID:27680398

  7. Sex differences in creatine kinase after acute heavy resistance exercise on circulating granulocyte estradiol receptors.

    PubMed

    Wolf, Megan R; Fragala, Maren S; Volek, Jeff S; Denegar, Craig R; Anderson, Jeffrey M; Comstock, Brett A; Dunn-Lewis, Courtenay; Hooper, David R; Szivak, Tunde K; Luk, Hui-Ying; Maresh, Carl M; Häkkinen, Keijo; Kraemer, William J

    2012-09-01

    Previous research has shown reduced tissue disruption and inflammatory responses in women as compared to men following acute strenuous exercise. While the mechanism of this action is not known, estrogen may reduce the inflammatory response through its interaction with granulocytes. The purpose of this study was to determine if estrogen receptor β expression on granulocytes is related to sex differences in tissue disruption in response to an acute heavy resistance exercise protocol. Seven healthy, resistance-trained, eumenorrheic women (23 ± 3 years, 169 ± 9.1 cm, 66.4 ± 10.5 kg) and 8 healthy, resistance-trained men (25 ± 5 years, 178 ± 6.7 cm, 82.3 ± 9.33 kg) volunteered to participate in the study. Subjects performed an acute resistance exercise test consisting of six sets of five squats at 90% of the subject's one repetition maximum. Blood samples were obtained pre-, mid-, post-, and 1-, 6-, and 24-h postexercise. Blood samples were analyzed for 17-β-estradiol by ELISA, creatine kinase by colorimetric enzyme immunoassay, and estradiol receptors on circulating granulocytes through flow cytometry. Men had higher CK concentrations than women at baseline/control. Men had significantly higher CK concentrations at 24-h postexercise than women. No significant changes in estradiol β receptors were expressed on granulocytes after exercise or between sexes. While sex differences occur in CK activity in response to strenuous eccentric exercise, they may not be related to estradiol receptor β expression on granulocytes. Thus, although there are sex differences in CK expression following acute resistance exercise, the differences may not be attributable to estrogen receptor β expression on granulocytes.

  8. Progesterone and estradiol-17β as a potential method for pregnancy diagnosis in the collared peccary (Pecari tajacu).

    PubMed

    Mayor, Pedro; Guimarães, Diva Anelie; López-Béjar, Manel

    2012-12-01

    In this study, the period of pregnancy of nine collared peccary females has been monitored through the analysis of serum progesterone and estradiol-17β profiles. Serum concentrations of progesterone increased by Day 4 after conception, reaching concentrations of 33.4±5.6 ng/mL on Day 10. Between Days 10 and 130 progesterone values were maintained between 20 and 60 ng/mL. In the collared peccary, embryonic estradiol synthesis is first observed in the systemic circulation by Day 15 of pregnancy. Between Days 0 and 50 of pregnancy, average estradiol-17β concentrations were between 0 and 30 pg/mL. From Day 75 of pregnancy onwards, estradiol concentrations were constantly increasing, reaching maximum concentrations (131.4±40.8 pg/mL) on the day of parturition. The combined study of serum progesterone and estradiol-17β concentrations as a potential method for early pregnancy diagnosis presented the best overall accuracy (73%) when the threshold was established at 20 ng/mL serum progesterone and 20 pg/mL serum estradiol. Nevertheless, the accuracy for diagnosing pregnancy of females at mid and late pregnancy was 78% and 95%, respectively. The analysis of the sexual hormones during pregnancy could be a useful tool as a potential pregnancy diagnosis and an efficient predictor of the day of parturition in the captive collared peccary.

  9. Preventive Role of Estradiol on Kidney Injury Induced by Renal Ischemia-Reperfusion in Male and Female Rats

    PubMed Central

    Iran-Nejad, Akram; Nematbakhsh, Mehdi; Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir

    2015-01-01

    Background: Renal ischemia-reperfusion (RIR) is the main cause of renal failure. The incidence of RIR injury seems to be gender-related due to female sex hormone; estrogen. This study was designed to investigate the protective role of estrogen against RIR injury in male and ovariectomized female rats. Methods: Thirty-nine Wistar rats were used in this study as male and ovariectomized female rats in the sham-operated, RIR, and estradiol-treated plus RIR groups. The RIR was induced by clamping the renal vessels for 45 min and then 24 h of reperfusion. All animals finally were sacrificed for the measurements. Results: The serum levels of creatinine and blood urea nitrogen and kidney tissue damage score significantly increased in both male and female RIR rats (P < 0.05). Estradiol however significantly attenuated theses parameters (P < 0.05) toward normal levels in female (P < 0.05), but not in male rats. Kidney weight increased in both genders and estradiol intensified it in the male rats (P < 0.05). Uterus weight was increased by estradiol in female rats (P < 0.05) and testis weight did not alter in male rats. Conclusions: Estradiol demonstrated a protective role against RIR injury in female rats; however, estradiol as an antioxidant could not protect the male kidney from RIR injury. PMID:25830011

  10. Estradiol levels in women predict skin conductance response but not valence and expectancy ratings in conditioned fear extinction.

    PubMed

    White, Emily C; Graham, Bronwyn M

    2016-10-01

    Anxiety disorders are more prevalent in women than men. One contributing factor may be the sex hormone estradiol, which is known to impact the long term recall of conditioned fear extinction, a laboratory procedure that forms the basis of exposure therapy for anxiety disorders. To date, the literature examining estradiol and fear extinction in humans has focused primarily on physiological measures of fear, such as skin conductance response (SCR) and fear potentiated startle. This is surprising, given that models of anxiety identify at least three important components: physiological symptoms, cognitive beliefs, and avoidance behavior. To help address this gap, we exposed women with naturally high (n=20) or low estradiol (n=19), women using hormonal contraceptives (n=16), and a male control group (n=18) to a fear extinction task, and measured SCR, US expectancy and CS valence ratings. During extinction recall, low estradiol was associated with greater recovery of SCR, but was not related to US expectancy or CS evaluation. Importantly, women using hormonal contraceptives showed a dissociation between SCR and cognitive beliefs: they exhibited a greater recovery of SCR during extinction recall, yet reported similar US expectancy and CS valence ratings to the other female groups. This divergence underscores the importance of assessing multiple measures of fear when examining the role of estradiol in human fear extinction, especially when considering the potential of estradiol as an enhancement for psychological treatments for anxiety disorders. PMID:27544848

  11. Estradiol induces endothelial cell migration and proliferation through estrogen receptor-enhanced RhoA/ROCK pathway.

    PubMed

    Oviedo, Pilar J; Sobrino, Agua; Laguna-Fernandez, Andrés; Novella, Susana; Tarín, Juan J; García-Pérez, Miguel-Angel; Sanchís, Juan; Cano, Antonio; Hermenegildo, Carlos

    2011-03-30

    Migration and proliferation of endothelial cells are involved in re-endothelialization and angiogenesis, two important cardiovascular processes that are increased in response to estrogens. RhoA, a small GTPase which controls multiple cellular processes, is involved in the control of cell migration and proliferation. Our aim was to study the role of RhoA on estradiol-induced migration and proliferation and its dependence on estrogen receptors activity. Human umbilical vein endothelial cells were stimulated with estradiol, in the presence or absence of ICI 182780 (estrogen receptors antagonist) and Y-27632 (Rho kinase inhibitor). Estradiol increased Rho GEF-1 gene expression and RhoA (gene and protein expression and activity) in an estrogen receptor-dependent manner. Cell migration, stress fiber formation and cell proliferation were increased in response to estradiol and were also dependent on the estrogen receptors and RhoA activation. Estradiol decreased p27 levels, and significantly raised the expression of cyclins and CDK. These effects were counteracted by the use of either ICI 182780 or Y-27632. In conclusion, estradiol enhances the RhoA/ROCK pathway and increases cell cycle-related protein expression by acting through estrogen receptors. This results in an enhanced migration and proliferation of endothelial cells.

  12. Estradiol induces gene proximity and MLL-MLLT3 fusion in an activation-induced cytidine deaminase-mediated pathway.

    PubMed

    Wright, Rebecca L; Slemmons, Katherine K; Vaughan, Andrew T M

    2015-05-01

    Epidemiological data have linked birth control formulations to an increased risk of infant acute leukemia involving MLL rearrangements. Reverse transcription polymerase chain reaction (RT-PCR) studies showed that 10 nM estradiol enhanced MLL transcription in addition to its common translocation partners, MLLT2 (AF4) and MLLT3 (AF9). The same concentration of estradiol triggered MLL and MLLT3 co-localization without affecting the interaction of genes located on the same chromosomes. Estradiol also stimulated the generation of MLL-MLLT3 fusion transcripts as seen by RT-PCR. RNAi knockdown of activation-induced cytidine deaminase (AICDA) suppressed the induction of MLL-MLLT3 fusion transcript formation observed with estradiol. Additionally, chromatin immunoprecipitation (ChIP) analysis showed estradiol dependent localization of AICDA in MLL intron 11, upstream of a hotspot for both DNA cleavage and rearrangement, but not downstream within intron 12. Combined, these studies show that levels of estradiol consistent with that observed during pregnancy have the potential to initiate MLL fusions through an AICDA-mediated mechanism.

  13. Estradiol levels in women predict skin conductance response but not valence and expectancy ratings in conditioned fear extinction.

    PubMed

    White, Emily C; Graham, Bronwyn M

    2016-10-01

    Anxiety disorders are more prevalent in women than men. One contributing factor may be the sex hormone estradiol, which is known to impact the long term recall of conditioned fear extinction, a laboratory procedure that forms the basis of exposure therapy for anxiety disorders. To date, the literature examining estradiol and fear extinction in humans has focused primarily on physiological measures of fear, such as skin conductance response (SCR) and fear potentiated startle. This is surprising, given that models of anxiety identify at least three important components: physiological symptoms, cognitive beliefs, and avoidance behavior. To help address this gap, we exposed women with naturally high (n=20) or low estradiol (n=19), women using hormonal contraceptives (n=16), and a male control group (n=18) to a fear extinction task, and measured SCR, US expectancy and CS valence ratings. During extinction recall, low estradiol was associated with greater recovery of SCR, but was not related to US expectancy or CS evaluation. Importantly, women using hormonal contraceptives showed a dissociation between SCR and cognitive beliefs: they exhibited a greater recovery of SCR during extinction recall, yet reported similar US expectancy and CS valence ratings to the other female groups. This divergence underscores the importance of assessing multiple measures of fear when examining the role of estradiol in human fear extinction, especially when considering the potential of estradiol as an enhancement for psychological treatments for anxiety disorders.

  14. Hormone replacement with 17β-estradiol plus dihydrotestosterone restores male sexual behavior in rats treated neonatally with clomipramine.

    PubMed

    Limón-Morales, Ofelia; Soria-Fregozo, Cesar; Arteaga-Silva, Marcela; González, Marisela Hernández; Vázquez-Palacios, Gonzalo; Bonilla-Jaime, Herlinda

    2014-11-01

    Male sexual behavior (MSB) in rodents, in both its consummatory and motivational components, is regulated by hormones such as testosterone, 17β-estradiol and 5-α-dihydrotestosterone. In experiments, neonatal treatment with clomipramine (CMI; a serotonin reuptake inhibitor) reproduces some of the signs of depression in adult age, including reduced sexual behavior manifested in a lower percentage of subjects that mount, intromit and ejaculate, although their testosterone levels were not altered. However, the effect of this treatment on estrogen levels and the consequences of hormone substitution using 17β-estradiol and 5-α-dihydrotestosterone on the expression of male sexual behavior are still unknown. Therefore, the objective of the present study was to analyze the effect of neonatal treatment with CMI on plasma testosterone and 17β-estradiol levels, and the role of testosterone, 17β-estradiol and 5-α-dihydrotestosterone in altering the consummatory and motivational components of sexual behavior in male rats. To this end, it analyzed the copulatory parameters and sexual incentive motivation (SIM) of rats treated with CMI under two conditions: basal and post-hormone replacements. Neonatal treatment with CMI did not affect plasma testosterone or 17β-estradiol concentrations, but did decrease both the consummatory component and sexual motivation according to the results of the SIM test. These aspects were recovered after administering 17β-estradiol +5-α-dihydrotestosterone, but not testosterone.

  15. Doxorubicin loaded 17β-estradiol based SWNT dispersions for target specific killing of cancer cells.

    PubMed

    Ghosh, Moumita; Das, Prasanta Kumar

    2016-06-01

    The present work reports the synthesis of a 17β-estradiol based amphiphiles comprising of polyethylene glycol (PEG) moiety linked through succinic acid that non-covalently dispersed (76%) the single walled carbon nanotubes (SWNTs) in water. The superior exfoliation of carbon nanotubes was characterized by microscopic and spectroscopic studies. Significant stability of these SWNT dispersions was observed in the presence of protein in cell culture media and the nanohybrids were highly biocompatible toward mammalian cells. Anticancer drug doxorubicin loaded on these nanohybrids was selectively delivered within estrogen receptor rich cancer cells, MCF7 (breast cancer cell) and A549 (lung cancer cell). Microscopic studies showed the localization of doxorubicin within the cancer cell nucleus whereas no such localization was observed in ER negative cells. Both these ER positive cancer cells were killed by ∼3 fold higher efficiency than that of ER negative MDA-MB-231 (advanced breast cancer cell) and HeLa cells that are deprived of estrogen receptors. Thus, judiciously designed estradiol based nanohybrids proved to be excellent tool for SWNT dispersion and also for selectively killing of ER positive cancer cells. To the best of our knowledge, for the first time non-covalently modified SWNTs by estradiol based amphiphilic dispersing agent have been used for selective killing of ER positive cancer cells by doxorubicin loaded on dispersed SWNTs. It holds immense promise to be exploited as a cancer therapeutic agent. PMID:26970825

  16. Trait anxiety moderates the association between estradiol and dominance in women.

    PubMed

    Ziomkiewicz, Anna; Wichary, Szymon; Gomula, Aleksandra; Pawlowski, Boguslaw

    2015-05-01

    The aim of the study was to investigate the relationship between self-assessed social dominance trait and levels of free basal sex steroids: estradiol and testosterone, in reproductive age women. Polish urban women aged 24-35 (N = 72) filled in Trait Dominance-Submissiveness Scale (TDS) and State and Trait Anxiety Inventory (STAI). They also gave a single blood sample during the follicular phase of the following menstrual cycle. The blood sample was analyzed for concentration of free testosterone (T), estradiol (E2) and cortisol (C). We found that self-assessed social dominance was negatively associated with free E2 and E2 to T ratio. This general relationship was moderated by Trait Anxiety. Higher social dominance was associated with lower E2 and lower E2 to T ratio in moderate and highly anxious women. No such relationship was found in low anxious women. Results of this study evidence important contribution of estradiol and question the independent role of testosterone in shaping dominance in women. They might also suggest important biological and psychological cost of maintaining high social dominance in reproductive age women.

  17. Treatment of postmenopausal vaginal atrophy with 10-μg estradiol vaginal tablets.

    PubMed

    Panay, Nick; Maamari, Ricardo

    2012-03-01

    Postmenopausal estrogen deficiency can lead to symptoms of urogenital atrophy. Individuals with urogenital atrophy have symptoms that include vaginal dryness, vaginal and vulval irritation, vaginal soreness, pain and burning during urination (dysuria), increased vaginal discharge, vaginal odour, vaginal infections, recurrent urinary tract infections, pain associated with sexual activity (dyspareunia) and vaginal bleeding associated with sexual activity. Despite the frequency and effects of vaginal atrophy symptoms, they are often under-reported and, consequently, under-treated. Therefore, care of a menopausal woman should include a physical assessment of vaginal atrophy and a dialogue between the physician and the patient that explores existing symptoms and their effect on vulvovaginal health, sexuality and quality-of-life issues. The development of the ultra-low-dose 10-µg estradiol vaginal tablets is in line with the requirements of regulatory agencies and women's health societies regarding the use of the lowest effective hormonal dose. Because of its effectiveness and safety profiles, in addition to its minimal systemic absorption, the 10-µg estradiol vaginal tablet can offer greater reassurance to health-care providers and postmenopausal women with an annual estradiol administration of only 1.14 mg.

  18. The effects of estradiol on gonadotropin-releasing hormone neurons in the developing mouse brain.

    PubMed

    Grober, M S; Winterstein, G M; Ghazanfar, A A; Eroschenko, V P

    1998-12-01

    The hypothalamic-pituitary-gonadal (HPG) axis plays a critical role in the control of reproduction. Two key hormonal components of the HPG axis are gonadal steroids and gonadotropin-releasing hormone (GnRH). Gonadal steroids are known to organize the development of neural substrates which control adult reproductive behavior; GnRH is required for normal reproductive structure and function. The possibility that gonadal steroids may produce organizational changes in the pattern of GnRH staining observed in the brain is investigated through the use of injections of estradiol to neonatal mice and subsequent GnRH immunocytochemistry at 2 months of age. Our results indicate that the number of GnRH-immunoreactive (GnRH-ir) cells is normally lower in females than males. Estradiol did not affect the number of GnRH-ir cells in females, but significantly increased the number of GnRH-ir cells in males, suggesting that early exposure to estradiol results in masculinization of the GnRH axis of males.

  19. Changes in the uptake of tritiated estradiol in the hypothalamus and adenohypophysis of old female rats.

    PubMed

    Peng, M T; Peng, Y M

    1973-07-01

    The dysfunction of the hypothalamic-pituitary axis of 32 old female rats was elucidated. Old rats were over 20 months of age; young rats were only several months old. Rats were divided into 3 groups according to vaginal smears and ovarian and uterine findings during laparotomy: 1) prolonged vaginal cornification with polyfollicular ovaries (PVC), 2) anestrus with atropic ovaries and uterus (ANE), and 3) prolonged diestrus with hyperluteinized ovaries and hypertropic uterus (pseudopregnancy, PSP). Even 1 week after ovariectomy the uteri of old rats with PVC (11) or PSP (5) were heavier than the uteri of young adults oq old rats with ANE (20). The pituitaries of young rats (32) were lighter than those of old rats (32). In vitro tritiated estradiol uptakes of anterior hypothalamus, adenohypophysis and uterus of old rats with PVC; anterior and posterior hypothalamus, adenohypophysisand uterus of old rats with ANE (10) and adenohypophysis of old rats with PSP were each significantly lower than the corresponding uptakes in the young rats. Further investigation using young rats with induced PSP, indicated that the decreased tritiated estradiol uptake in the adenohypophysis of old PSP rats was due to old age and unrelated to PSP. In vivo tritiated estradiol uptakes of anterior hypothalamus and adenohypophysis of old rats with PVC or ANE and of uterus of old rats with PVC were significantly lower than the corresponding uptakes in the young rats.

  20. Methamphetamine-induced conditioned place preference is facilitated by estradiol pretreatment in female mice.

    PubMed

    Chen, H H; Yang, Y K; Yeh, T L; Cherng, C F G; Hsu, H C; Hsiao, S Y; Yu, L

    2003-12-31

    Ovarian hormones were well documented to modulate the dopamine release in the central dopaminergic systems. The dopamine-releasing effects in the nucleus accumbens, a major target of the mesolimbicortical dopaminergic system, were closely associated with the reinforcing effects of two psychomotor stimulants, cocaine and methamphetamine. This study aimed to examine the sex differences in the cocaine- and methamphetamine-reinforcing behavior, conditioned place preference. In addition, the modulating effects of estradiol and progesterone on methamphetamine-induced conditioned place preference were investigated in both sexes of adult gonadectomized mice. There was no sex difference in the sensitivity to the cocaine (5 mg/kg)-induced conditioned place preference. However, female mice exhibited a more potent methamphetamine (1 mg/kg)-induced conditioned place preference than did male mice. Moreover, pretreatment with estradiol for two consecutive days before the beginning of the conditioning and throughout the four daily conditionings (0.47 microg/day for totally six days) effectively facilitated methamphetamine-induced conditioned place preference in gonadectomized female mice, but not in gonadectomized male mice. Progesterone, under a similar treatment regimen (0.47 microg/day for six consecutive days), did not alter the methamphetamine-induced conditioned place preference in either sex of gonadectomized mice. Taken together, we conclude that the facilitating effects of estradiol on methamphetamine-induced conditioned place preference could be sex-dependent with an eminent sensitivity associated with the adult female mice.

  1. Estradiol-Treated Female Mice as Surrogate Hosts for Neisseria gonorrhoeae Genital Tract Infections.

    PubMed

    Jerse, Ann E; Wu, Hong; Packiam, Mathanraj; Vonck, Rachel A; Begum, Afrin A; Garvin, Lotisha E

    2011-01-01

    Historically, animal modeling of gonorrhea has been hampered by the exclusive adaptation of Neisseria gonorrhoeae to humans. Genital tract infection can be established in female mice that are treated with 17β-estradiol, however, and many features of experimental murine infection mimic human infection. Here we review the colonization kinetics and host response to experimental murine gonococcal infection, including mouse strain differences and evidence that IL-17 responses, toll-like receptor 4, and T regulatory cells play a role in infection. We also discuss the strengths and limitations of the mouse system and the potential of transgenic mice to circumvent host restrictions. Additionally, we review studies with genetically defined mutants that demonstrated a role for sialyltransferase and the MtrC-MtrD-MtrE active efflux pump in evading innate defenses in vivo, but not for factors hypothesized to protect against the phagocytic respiratory burst and H(2)O(2)-producing lactobacilli. Studies using estradiol-treated mice have also revealed the existence of non-host-restricted iron sources in the female genital tract and the influence of hormonal factors on colonization kinetics and selection for opacity (Opa) protein expression. Recent work by others with estradiol-treated mice that are transgenic for human carcinoembryonic adhesion molecules (CEACAMs) supports a role for Opa proteins in enhancing cellular attachment and thus reduced shedding of N. gonorrhoeae. Finally we discuss the use of the mouse model in product testing and a recently developed gonorrhea chlamydia coinfection model.

  2. Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection

    NASA Astrophysics Data System (ADS)

    Xu, Yun; Zhang, Wenri; Klaus, Judith; Young, Jennifer; Koerner, Ines; Sheldahl, Laird C.; Hurn, Patricia D.; Martínez-Murillo, Francisco; Alkayed, Nabil J.

    2006-09-01

    Estrogen reduces brain injury after experimental cerebral ischemia in part through a genomic mechanism of action. Using DNA microarrays, we analyzed the genomic response of the brain to estradiol, and we identified a transcript, cocaine- and amphetamine-regulated transcript (CART), that is highly induced in the cerebral cortex by estradiol under ischemic conditions. Using in vitro and in vivo models of neural injury, we confirmed and characterized CART mRNA and protein up-regulation by estradiol in surviving neurons, and we demonstrated that i.v. administration of a rat CART peptide is protective against ischemic brain injury in vivo. We further demonstrated binding of cAMP response element (CRE)-binding protein to a CART promoter CRE site in ischemic brain and rapid activation by CART of ERK in primary cultured cortical neurons. The findings suggest that CART is an important player in estrogen-mediated neuroprotection and a potential therapeutic agent for stroke and other neurodegenerative diseases. ischemia | stroke | estrogen

  3. Relationship between estradiol 16 alpha-hydroxylation and human papillomavirus infection in cervical cell transformation.

    PubMed

    Salazar, E L; Mercado, E; Sojo, I; Salcedo, M

    2001-10-01

    The ovarian steroid hormone estradiol and its metabolite estrone were examined in 45 normal women and 127 premenopausal women with precancerous cervical lesions. Interviews, colposcopy and cervical scrapings were performed. The mean +/- SD values for estradiol and estrone were 0.07 +/- 0.08 ng/ml and 0.06 +/- 0.02 ng/ml, respectively in normal subjects. Corresponding data in patients with cervical intraepithelial neoplasia alone or in association with human papillomavirus (HPV) infection were 0.074 +/- 0.03 ng/ml and 0.076 +/- 0.03 ng/ml or 0.080 +/- 0.03 ng/ml and 0.148 +/- 0.02 ng/ml, respectively, which revealed a significantly greater extent of estrogenic action in the latter population (p < 0.05). We considered that the presence of HPV infection probably increased 16 alpha-hydroxylation of estradiol, providing a possible link between the viral and hormonal elements, possibly having a bearing on the etiology of the disease.

  4. Localization of /sup 3/H-estradiol in the reproductive organs of male and female baboons

    SciTech Connect

    Weaker, F.J.; Sheridan, P.J.

    1982-05-01

    The uptake and retention of radiolabeled estradiol by both the male and female reproductive organs were examined in the baboon. Two male and two female baboons were injected intracardially with 1 microgram/kg body weight of /sup 3/H-estradiol and two animals, one male and one female, were injected with both labeled and 100 micrograms/kg body weight of unlabeled estradiol. One and a half hours after the injections, the animals were sacrificed and the uterus, cervix, vagina, oviduct, seminal vesicles, and prostate gland were removed and processed for autoradiography. The stratified squamous epithelia of the cervix and vagina demonstrated a light uptake of the label in the germinative, but not in the superficial cell layers. The columnar cells lining the oviduct and uterine glands were labeled, whereas the luminal epithelium of the uterus and the glandular epithelia of the seminal vesicles and prostate gland did not sequester the tritiated steroid. The interstitial cells of all the organs studied demonstrated a moderate to heavy uptake of the radioactivity, whereas the smooth muscle cells were lightly labeled except in the vagina, in which these cells displayed a moderate number of silver grains.

  5. Lack of support for relation between woman's masculinity preference, estradiol level and mating context.

    PubMed

    Marcinkowska, Urszula M; Ellison, Peter T; Galbarczyk, Andrzej; Milkowska, Karolina; Pawlowski, Boguslaw; Thune, Inger; Jasienska, Grazyna

    2016-02-01

    It has been proposed that women's preferences for male facial sexual dimorphism are positively correlated with conception probability and differ between short- and long-term mating contexts. In this study, we tested this assumption by analyzing relationships between estradiol levels to the women's preferences of male faces that were manipulated to vary in masculinity. Estradiol was measured in daily saliva samples throughout the entire menstrual cycle collected by Polish women with regular menstrual cycles. In our analyses, we included the three most commonly used definitions of the fertile window in the literature. After computing the overall masculinity preference of each participant and measuring hormone levels, we found that i) the timing of ovulation varied greatly among women (between -11 and -17days from the onset of the next menses, counting backwards), ii) there was no relationship between daily, measured during the day of the test (N=83) or average for the cycle (N=115) estradiol levels and masculinity preferences, iii) there were no differences in masculinity preferences between women in low- and high-conception probability phases of the cycle, and iv) there were no differences in masculinity preferences between short- and long-term mating contexts. Our results do not support the idea that women's preferences for a potential sexual partner's facial masculinity fluctuate throughout the cycle.

  6. Estradiol modulates recovery of REM sleep in a time-of-day-dependent manner.

    PubMed

    Schwartz, Michael D; Mong, Jessica A

    2013-08-01

    Ovarian hormones are thought to modulate sleep and fluctuations in the hormonal milieu are coincident with sleep complaints in women. In female rats, estradiol increases waking and suppresses sleep. In this study, we asked whether this effect is mediated via circadian or homeostatic regulatory mechanisms. Ovariectomized female rats received daily injections of estradiol benzoate (EB) or sesame oil that mimicked the rapid increase and subsequent decline of circulating estradiol at proestrus. In one experiment, animals were sleep deprived for 6 h starting at lights-on, so that recovery began in the mid-light phase; in the second experiment, animals were sleep deprived starting in the mid-light phase, so that recovery began at lights-off. EB suppressed baseline rapid eye movement (REM) and non-REM (NREM) sleep and increased waking in the dark phase. In both experiments, EB enhanced REM recovery in the light phase while suppressing it in the dark compared with oil; this effect was most pronounced in the first 6 h of recovery. By contrast, NREM recovery was largely unaffected by EB. In summary, EB enhanced waking and suppressed sleep, particularly REM sleep, in the dark under baseline and recovery conditions. These strong temporally dependent effects suggest that EB consolidates circadian sleep-wake rhythms in female rats.

  7. Age-specific reference values for serum FSH and estradiol levels throughout the reproductive period.

    PubMed

    Grisendi, Valentina; Spada, Elena; Argento, Cindy; Plebani, Maddalena; Milani, Silvano; Seracchioli, Renato; Volpe, Annibale; La Marca, Antonio

    2014-06-01

    High serum day 3 FSH levels are associated with poor ovarian reserve and reduced fertility, but the interpretation of FSH values according to age is still not univocal. The purpose of this study was to determine age-dependent reference values in women with regular menstrual cycles and FSH as a guide for specialists. The study was performed at the Department of Mother-Infant of a University-based tertiary care centre. One-hundred ninety-two healthy normal menstruating women were recruited for the study. All patients attended the department on menstrual cycle day 3 for a blood sample for FSH and estradiol determination. A linear relationship between FSH or estradiol serum levels and age was observed. The FSH level increased by 0.11 IU for every year of age (1 IU for every 9 years of age). The values of FSH and estradiol corresponding to the 5th, 25th, 50th, 75th, 95th centiles for any specific age have been calculated. Serum FSH levels need to be interpreted according to age-dependent reference values. Serum FSH levels on 95th centile for any age may represent a warning sign for reduced ovarian reserve.

  8. Relation among cytochrome P450, AH-active PCB congeners and dioxin equivalents in pipping black-crowned night-heron embryos

    USGS Publications Warehouse

    Rattner, B.A.; Hatfield, J.S.; Melancon, M.J.; Custer, T.W.; Tillitt, D.E.

    1994-01-01

    Pipping black-crowned night-heron (Nycticorax nycticorax) embryos were collected from a relatively uncontaminated site (next to Chincoteague National Wildlife Refuge, VA) and three polluted sites (Cat Island, Green Bay, Lake Michigan, WI; Bair Island, San Francisco Bay, CA; West Marin Island, San Francisco Bay, CA). Hepatic cytochrome P-450-associated monooxygenases and cytochrome P-450 proteins, induced up to 85-fold relative to the reference site, were associated with concentrations of total polychlorinated biphenyls (PCBs) and 11 PCB congeners that are presumed to express toxicity through the arylhydrocarbon (Ah) receptor. Multiple regression revealed that up to 86% of the variation of cytochrome P450 measurements was accounted for by variation in the concentration of these PCB congeners. Toxic equivalents (TEQs) of sample extracts, predicted mathematically (summed product of PCB congener concentrations and toxic equivalency factors), and dioxin equivalents (TCDD-EQs), derived by bioassay (ethoxyresorufin-O-dealkylase activity of treated H4IIE rat hepatoma cells), were greatest in Cat Island samples. Cytochrome P450-associated monooxygenases and cytochrome P450 proteins were related to TEQs and TCDD-EQs; adjusted r-2 often exceeded 0.5 for the relation among mathematically predicted TEQs and cytochrome P450 measurements. These data extend previous observations in heron embryos of an association between P450 and total PCB burdens to include Ah-active PCB congeners, and presumably other compounds, which interact similarly with the Ah receptor. Benzyloxyresorufin O-dealkylase, ethoxyresorufin O-dealkylase, and cytochrome P450 1A appear to be the most reliable measures of exposure to Ah-active PCB congeners in black-crowned night-heron embryos. These findings provide further evidence that cytochrome P450-associated parameters have considerable value as a biomarker for assessing environmental contamination of wetlands.

  9. Relation among cytochrome P450, Ah-active PCB congeners and dioxin equivalents in pipping black-crowned night-heron embryos

    SciTech Connect

    Rattner, B.A.; Hatfield, J.S.; Melancon, M.J.; Custer, T.W. . Patuxent Environmental Science Center); Tillitt, D.E. . Midwest Science Center)

    1994-11-01

    Pipping black-crowned night-heron (Nycticorax nycticorax) embryos were collected from a relatively uncontaminated site (next to Chincoteague National Wildlife Refuge, VA) and three polluted sites (Cat Island, Green Bay, Lake Michigan, WI; Bair Island, San Francisco Bay, CA; West Marin Island, San Francisco Bay, CA). Hepatic cytochrome P450-associated mono-oxygenates and cytochrome P450 proteins, induced up to 85-fold relative to the reference site, were associated with concentrations of total polychlorinated biphenyls (PCBs) and 11 PCB congeners that are presumed to express toxicity through the arylhydrocarbon (Ah) receptor. Multiple regression revealed that up to 86% of the variation of cytochrome P450 measurements was accounted for by variation in the concentration of these PCB congeners. Toxic equivalents (TEQs) of sample extracts, predicted mathematically (summed product of PCB congener concentrations and toxic equivalency factors), and dioxin equivalents (TCDD-EQs), derived by bioassay (ethoxyresorufin-O-dealkylase activity of treated H4IIE rat hepatoma cells), were greatest in Cat Island samples. Cytochrome P450-associated monooxygenases and cytochrome P450 proteins were related to TEQs and TCDD-EQs; adjusted r[sup 2] often exceeded 0.5 for the relation among mathematically predicted TEQs and cytochrome P450 measurements. These data extend previous observations in heron embryos of an association between P450 and total PCB burdens to include Ah-active PCB congeners, and presumably other compounds, which interact similarly with the AH receptor. Benzyloxyresorufin O-dealkylase, ethoxyresorufin O-dealkylase, and cytochrome P450 1A appear to be the most reliable measures of exposure to Ah-active PCB congeners in black-crowned night-heron embryos. These findings provide further evidence that cytochrome P450-associated parameters have considerable value as a biomarker for assessing environmental contamination of wetlands.

  10. Relation among cytochrome P450, Ah-active PCB congeners and dioxin equivalents in pipping black- crowned night-heron embryos

    USGS Publications Warehouse

    Rattner, B.A.; Hatfield, J.S.; Melancon, M.J.; Custer, T.W.; Tillitt, D.E.

    1994-01-01

    Pipping black-crowned night-heron (Nycticorax nycticorax) embryos were collected from a relatively uncontaminated site (next to Chincoteague National Wildlife Refuge, VA) and three polluted sites (Cat Island, Green Bay, Lake Michigan, WI; Bair Island, San Francisco Bay, CA; West Marin Island, San Francisco Bay, CA). Hepatic cytochrome P450-associated monooxygenases and cytochrome P450 proteins, induced up to 85- fold relative to the reference site, were associated with concentrations of total polychlorinated biphenyls (PCBs) and 11 PCB congeners that are presumed to express toxicity through the arylhydrocarbon (Ah) receptor. Multiple regression revealed that up to 86% of the variati