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Sample records for estradiol affects liver

  1. Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

    SciTech Connect

    Moreira, Paula I.; Custodio, Jose B.A.; Nunes, Elsa; Moreno, Antonio; Seica, Raquel; Oliveira, Catarina R.; Santos, Maria S. . E-mail: mssantos@ci.uc.pt

    2007-05-15

    Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17{beta}-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca{sup 2+} delaying the opening of the permeability transition pore. The presence of 25 {mu}M E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H{sub 2}O{sub 2} in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered.

  2. Testosterone and estradiol treatments differently affect pituitary-thyroid axis and liver deiodinase 1 activity in orchidectomized middle-aged rats.

    PubMed

    Šošić-Jurjević, B; Filipović, B; Renko, K; Miler, M; Trifunović, S; Ajdžanovič, V; Kӧhrle, J; Milošević, V

    2015-12-01

    We previously reported that orchidectomy (Orx) of middle-aged rats (15-16-month-old; MA) slightly affected pituitary-thyroid axis, but decreased liver deiodinase (Dio) type 1 and pituitary Dio2 enzyme activities. At present, we examined the effects of subsequent testosterone-propionate treatment (5mg/kg; Orx+T), and compared the effects of testosterone with the effects of estradiol-dipropionate (0.06mg/kg; Orx+E) treatment. Hormones were subcutaneously administered, daily, for three weeks, while Orx and sham-operated (SO) controls received only the vehicle. The applied dose of T did not alter serum TSH, T4 and T3 concentrations in Orx- MA, though it increased TSH when administrated to Orx young adults (2.5-month-old; Orx-YA). However, pituitaries of Orx-MA+T rats had higher relative intensity of immunofluorescence (RIF) for TSHβ; in their thyroids we found increased volume and height of follicular epithelium, decreased volume of the colloid and higher RIF for T4-bound to thyroglobulin (Tg-T4). Liver Dio1 activity was increased. E-treatment did not affect serum hormone levels, pituitary RIF for TSHβ, or liver Dio1 activity in Orx-MA rats. Thyroids had decreased relative volume and height of follicular epithelium, increased relative volume of the colloid, decreased volume of sodium-iodide symporter-immunopositive epithelium and lower RIF for Tg-T4. Detected changes were statistically significant. In conclusion, androgenization enhanced pituitary TSHβ RIF, thyroid activation and liver Dio1 enzyme activity in Orx-MA, without elevating serum TSH as in Orx-YA rats. Estrogenization induced pituitary enlargement with no effect on pituitary TSHβ RIF, serum TSH or liver Dio1 activity. E also induced alterations in thyroid histology that indicate mild suppression of its functioning, and contributed to thyroid blood vessel enlargement in Orx-MA rats. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  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. 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...

  6. Lipid Profiling and Transcriptomic Analysis Reveals a Functional Interplay between Estradiol and Growth Hormone in Liver

    PubMed Central

    Fernández-Pérez, Leandro; Santana-Farré, Ruymán; de Mirecki-Garrido, Mercedes; García, Irma; Guerra, Borja; Mateo-Díaz, Carlos; Iglesias-Gato, Diego; Díaz-Chico, Juan Carlos; Flores-Morales, Amilcar; Díaz, Mario

    2014-01-01

    17β-estradiol (E2) may interfere with endocrine, metabolic, and gender-differentiated functions in liver in both females and males. Indirect mechanisms play a crucial role because of the E2 influence on the pituitary GH secretion and the GHR-JAK2-STAT5 signaling pathway in the target tissues. E2, through its interaction with the estrogen receptor, exerts direct effects on liver. Hypothyroidism also affects endocrine and metabolic functions of the liver, rendering a metabolic phenotype with features that mimic deficiencies in E2 or GH. In this work, we combined the lipid and transcriptomic analysis to obtain comprehensive information on the molecular mechanisms of E2 effects, alone and in combination with GH, to regulate liver functions in males. We used the adult hypothyroid-orchidectomized rat model to minimize the influence of internal hormones on E2 treatment and to explore its role in male-differentiated functions. E2 influenced genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, immune, and male-specific responses. E2 induced a female-pattern of gene expression and inhibited GH-regulated STAT5b targeted genes. E2 did not prevent the inhibitory effects of GH on urea and amino acid metabolism-related genes. The combination of E2 and GH decreased transcriptional immune responses. E2 decreased the hepatic content of saturated fatty acids and induced a transcriptional program that seems to be mediated by the activation of PPARα. In contrast, GH inhibited fatty acid oxidation. Both E2 and GH replacements reduced hepatic CHO levels and increased the formation of cholesterol esters and triacylglycerols. Notably, the hepatic lipid profiles were endowed with singular fingerprints that may be used to segregate the effects of different hormonal replacements. In summary, we provide in vivo evidence that E2 has a significant impact on lipid content and transcriptome in male liver and that E2 exerts a marked influence on

  7. Expression profile of early estradiol-responsive genes in cynomolgus macaque liver: implications for drug-metabolizing enzymes.

    PubMed

    Ise, Ryota; Kito, Go; Uno, Yasuhiro

    2012-01-01

    Estrogen plays important roles in estrogen-responsive tissues, such as mammary glands, ovaries, and the uterus. In the liver, the major drug metabolizing organ, estrogen is known to regulate expression of some drug-metabolizing enzymes. Due to the lack of information on the role of estrogen in hepatic gene expression in primate species, we previously investigated the late response of hepatic gene expression to estradiol in cynomolgus macaques. To understand the early response of hepatic gene expression to estradiol, in this study, microarray analysis was conducted using cynomolgus macaque liver samples collected at 1 h and 5 h after estradiol injection. Comparison of expression profiles in estradiol and solvent (control)-treated ovariectomized cynomolgus macaques revealed 27 differentially expressed genes (>2.0-fold), including 18 at 1 h and 9 at 5 h after estradiol injection. As indicated by Gene Ontology analysis, these genes were related to oxidoreductase activity and transferase activity, partly representing important aspects of drug-metabolizing enzymes. Further analysis by quantitative polymerase chain reaction revealed that estradiol down-regulated CYP2A24, CYP2C76, and CYP2E1 (>2.0-fold) at 1 h and up-regulated GSTM5 (>2.0-fold) at 5 h after estradiol injection. These results suggest that the short-term estradiol treatment influenced expression of hepatic genes, including drug-metabolizing enzyme genes, in cynomolgus macaque liver.

  8. Effects of estradiol on uterine perfusion in anesthetized cyclic mares affected with uterine vascular elastosis.

    PubMed

    Esteller-Vico, A; Liu, I K M; Vaughan, B; Steffey, E P; Brosnan, R J

    2016-01-01

    Uterine vascular elastosis in mares is characterized by degeneration of uterine vasculature through thickening of the elastin layers. Factors commonly associated with this degeneration include age, parity, and chronic uterine endometritis. Affected mares have also been shown to exhibit decreases in uterine blood flow and perfusion of the uterus. Due to the increased thickness of the elastin layers, we hypothesize that vasodilatation of the uterine vasculature is also impaired. To test the functionality of these vessels, we evaluated the vasodilatory effects of estradiol on the uterine vascular bed in mares with normal vasculature and mares with severe elastosis. Both groups were tested in estrus and diestrus. Fluorescent microspheres were used to determine basal blood perfusion, followed by the intravenous administration of 1.0 μg/kg of 17β-estradiol. After 90 min, perfusion was measured once again to determine the vascular response to estradiol. Control mares in estrus displayed a significant increase in total uterine blood flow after the administration of estradiol when compared to baseline levels. No other group had a significant increase in total blood flow and perfusion after estradiol administration. The administration of estradiol in control mares induced regional increases in perfusion in the uterine horns and uterine body during estrus and only in the uterine horns during diestrus. Mares affected by elastosis exhibited no regional differences in perfusion levels post-estradiol administration. The difference in the vasodilatory response induced by estradiol between reproductively healthy mares and mares affected with elastosis indicates that the functionality of the affected vessels is compromised.

  9. 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.

  10. 17β-estradiol in runoff as affected by various poultry litter application strategies.

    PubMed

    Delaune, P B; Moore, P A

    2013-02-01

    Steroidal hormones, which are excreted by all mammalian species, have received increasing attention in recent years due to potential environmental implications. The objective of this study was to evaluate 17β-estradiol concentrations in runoff water from plots receiving poultry litter applications using various management strategies. Treatments included the effects of 1) aluminum sulfate (alum) application rates to poultry litter; 2) time until the first runoff event occurs after poultry litter application; 3) poultry litter application rate; 4) fertilizer type; and 5) litter from birds fed modified diets. Rainfall simulators were used to cause continuous runoff from fertilized plots. Runoff samples were collected and analyzed for 17β-estradiol concentrations. Results showed that increasing alum additions to poultry litter decreased 17β-estradiol concentrations in runoff water. A significant exponential decline in 17β-estradiol runoff was also observed with increasing time until the first runoff event after litter application. Concentrations of 17β-estradiol in runoff water increased with increasing litter application rate and remained above background concentrations after three runoff events at higher application rates. Management practices such as diet modification and selection of fertilizer type were also shown to affect 17β-estradiol concentrations in runoff water. Although results from these experiments typically represented a worst case scenario since runoff events generally occurred immediately after litter application, the contaminant loss from pastures fertilized with poultry litter can be expected to be much lower than continual estradiol loadings observed from waste water treatment plants. Management practices such as alum amendment and application timing can significantly reduce the risk of 17β-estradiol losses in the environment.

  11. Effect of ethynyl estradiol on the secretion of hepatic triglyceride.

    PubMed

    Weinstein, I; Seedman, S; Veldhuis, M

    1975-05-01

    The concentrations of triglyceride in the blood of female rats increased 2- and 4-fold during treatment with 5 and 15 mug/kg of ethynyl estradiol, respectively. The rate of secretion of triglyceride increased 66% over controls with livers obtained from the rats administered ethynyl estradiol. Ethynyl estradiol induced a hypocholesterolemia in the donor animals but the secretion of cholesterol into the perfusate from livers obtained from these animal was not affected. Adrenal corticosterone levels were depressed 48% in animals receivint of ethynyl estradiol on the liver or secondary to other hormonal changes.

  12. Effect of hypocholesterolemic doses of 17 alpha-ethinyl estradiol on cholesterol balance in liver and extrahepatic tissues.

    PubMed

    Bertolotti, M; Spady, D K

    1996-08-01

    This study was performed to investigate the effects of 17 alpha-ethinyl estradiol, a potent hypocholesterolemic agent at pharmacological doses, on cholesterol balance in the liver and extrahepatic tissues of the rat in vivo. Female Sprague-Dawley rats were treated with 17 alpha-ethinyl estradiol (5 mg/kg per day s.c. for 5 days) or with 4-aminopyrazolo(3,4-d) pyrimidine (20 mg/kg per day i.p. for 3 days). Both drug regimens suppressed plasma total and low density lipoprotein-cholesterol by more than 80%. Analysis of the kinetic parameters of low density lipoprotein transport did not show increased receptor activity in extrahepatic tissues during either treatment. 17 alpha-Ethinyl estradiol significantly increased low density lipoprotein tissue spaces and clearance rates in the liver, with a 5-fold increase in low density lipoprotein-receptor activity, whereas 4-aminopyrazolo(3,4-d)pyrimidine suppressed hepatic transport of low density lipoprotein probably due to a nospecific toxic effect. Treatment with 17 alpha-ethinyl estradiol markedly enhanced the hepatic expression of low density lipoprotein-receptor protein and mRNA despite a 7-fold increase in hepatic cholesteryl ester levels. Finally, treatment with both drugs increased cholesterol synthesis in several extrahepatic tissues, such as adrenals, ovaries, small bowel, and spleen. These findings confirm that 17 alpha-ethinyl estradiol at pharmacological doses markedly increases synthesis and expression of low density lipoprotein-receptor in the liver. Hypocholesterolemia, whether induced by activation of low density lipoprotein-receptors or by other mechanisms, fails to up-regulate low density lipoprotein transport in extrahepatic tissues, which rather respond by increasing local sterol synthesis. This suggests the occurrence of separate regulatory mechanisms for low density lipoprotein transport and cholesterol synthesis.

  13. Isolation and characterization of three endosomal fractions from the liver of estradiol-treated rats

    SciTech Connect

    Belcher, J.D.; Hamilton, R.L.; Brady, S.E.; Hornick, C.A.; Jaeckle, S.; Schneider, W.J.; Havel, R.J.

    1987-10-01

    Three distinct endosomal fractions were isolated in high purity from livers of estradiol-treated rats. Each fraction had characteristic physical and ultrastructural properties, but the lipid composition and major proteins of their membranes were similar and differed from those derived from the Golgi apparatus. Injected radioiodinated low density lipoproteins accumulated first in the fraction of intermediate density and later in the low density fraction. The latter was composed almost exclusively of lipoprotein-filled multivesicular bodies, most of which had a single membranous appendage. The fraction of intermediate density was composed of lipoprotein-filled vesicles that were smaller than multivesicular bodies and also had membranous appendages. The high density fraction was composed of membranes resembling the appendages of the two vesicular fractions. All three fractions were enriched in receptors for low density lipoproteins and asialoglycoproteins, but receptor concentrations were considerably reduced in multivesicular bodies. The fraction of intermediate density may represent the compartment of uncoupling of receptor and ligand (CURL) described by Geuze et al. CURL vesicles may lose some of their appendages as multivesicular bodies are formed. The high density fraction than may represent a receptor-recycling compartment.

  14. Estradiol Modulates Membrane-Linked ATPases, Antioxidant Enzymes, Membrane Fluidity, Lipid Peroxidation, and Lipofuscin in Aged Rat Liver

    PubMed Central

    Kumar, Pardeep; Kale, R. K.; Baquer, Najma Zaheer

    2011-01-01

    Free radical production and oxidative stress are known to increase in liver during aging, and may contribute to the oxidative damage. These changes increase during menopausal condition in females when the level of estradiol is decreased. The objective of this study was to observe the changes in activities of membrane linked ATPases (Na+K+ ATPase, Ca2+ ATPase), antioxidant enzymes (superoxide dismutase, glutathione-S-transferase), lipid peroxidation levels, lipofuscin content and membrane fluidity occurring in livers of female rats of 3, 12 and 24 months age groups, and to see whether these changes are restored to 3 months control levels rats after exogenous administration of 17-β-estradiol (E2). The aged rats (12 and 24 months) were given subcutaneous injection of E2 (0.1 μg/g body weight) daily for one month. The results obtained in the present work revealed that normal aging was associated with significant decrease in the activities of membrane linked ATPases, antioxidant enzymes, membrane fluidity and an increase in lipid peroxidation and lipofuscin content in livers of aging female rats. The present study showed that E2 treatment reversed the changes to normal levels. E2 treatment may be beneficial in preventing some of the age related changes in the liver by increasing antioxidant defenses. PMID:22007298

  15. Estradiol decreases taurine level by reducing cysteine sulfinic acid decarboxylase via the estrogen receptor-α in female mice liver.

    PubMed

    Ma, Qiwang; Zhao, Jianjun; Cao, Wei; Liu, Jiali; Cui, Sheng

    2015-02-15

    Cysteine sulfinic acid decarboxylase (CSAD) and cysteine dioxygenase (CDO) are two rate-limiting enzymes in taurine de novo synthesis, and their expressions are associated with estrogen concentration. The present study was designed to determine the relationship between 17β-estradiol (E₂) and taurine in female mice liver. We initially observed the mice had lower levels of CSAD, CDO, and taurine during estrus than diestrus. We then, respectively, treated the ovariectomized mice, the cultured hepatocytes, and Hep G2 cells with different doses of E₂, and the CSAD and CDO expressions and taurine levels were analyzed. The results showed that E₂ decreased taurine level in the serum and the cultured cells by inhibiting CSAD and CDO expressions. Furthermore, we identified the molecular receptor types through which E₂ plays its role in regulating taurine synthesis, and our results showed that estrogen receptor-α (ERα) expression was much higher than estrogen receptor-β (ERβ) in the liver and hepatocytes, and the inhibiting effects of E₂ on CSAD, CDO, and taurine level were partially abrogated in the ICI-182,780-pretreated liver and hepatocytes, and in ERα knockout mice. These results indicate that estradiol decreases taurine content by reducing taurine biosynthetic enzyme expression in mice liver.

  16. A delay in pubertal onset affects the covariation of body weight, estradiol, and bone size.

    PubMed

    Yingling, Vanessa R

    2009-04-01

    The skeletal system functions as a locomotive organ and a mineral reservoir and combinations of genetic and environmental factors affect the skeletal system. Although delayed puberty is associated with compromised bone mass, suppression of estrogen should be beneficial to cortical strength. The purpose was to employ path analysis to study bone strength and delayed puberty. Forty-five female rats were randomly assigned to a control group (n = 15) and an experimental group (n = 30) that received injections of gonadotropin releasing hormone antagonist (GnRH-a). Causal models were constructed by specifying directed paths between bone traits. The first model tested the hypothesis that the functional relationships between bone traits and body weight were altered by a delay in pubertal onset. GnRH-a injections during puberty altered the covariation between body weight and bone size. The second model was constructed to test the hypothesis that variability in stiffness was causally related to variability in body weight. The model also tested the relationship between the periosteal and endocortical surfaces and their relationship to stiffness. There was no change in the relationship between the surfaces in the GnRH-a group. The third model determined the effect of estradiol on both total area and relative cortical area in both groups. The relationship between periosteal surface and serum estradiol levels was only significant during estrogen suppression. These data suggest that increases in body weight during or prior to puberty may not be protective of bone strength.

  17. Predominant 4-hydroxylation of estradiol by constitutive cytochrome P450s in the female ACI rat liver.

    PubMed

    Wilson, A M; Reed, G A

    2001-02-01

    The ACI rat is extremely sensitive to estrogens as mammary carcinogens, whereas the Sprague-Dawley strain is relatively resistant. Comparison of the disposition and effects of estrogens in these two strains should provide insights into the mechanisms of estrogen carcinogenicity. We have begun this investigation by comparing the metabolism of [(3)H]17beta-estradiol (E2) by liver microsomes prepared from female rats from each strain. Both strains produce estrone (E1) as the major product at E2 concentrations >1 microM, with smaller amounts of 2-hydroxy-E2 formed. As the E2 concentration is decreased, however, aromatic hydroxylation becomes a more dominant pathway for both strains. At starting E2 concentrations as low as 3 nM, Sprague-Dawley liver microsomes produced comparable yields of 2-hydroxy-E2 and E1. In contrast, ACI liver microsomes yielded a profound shift to aromatic hydroxylation as the dominant pathway as E2 concentrations dropped below 1 microM, and this shift reflected the production of 4-hydroxy-E2 as the predominant product. The apparent K(m) for 4-hydroxylation of E2 is <0.8 microM, as opposed to approximately 4 microM for 2-hydroxylation, suggesting that different cytochrome P450s (CYPs) are responsible. Western immunoblotting of the liver microsomal preparations from ACI and Sprague-Dawley rats for CYPs known to catalyze 2- and 4-hydroxylation of E2 revealed that both strains contained comparable amounts of CYP 2B1/2 and 3A1/2, but no detectable amounts of CYP 1B1, the proposed E2 4-hydroxylase. Although this enzyme is not a constitutive CYP in Sprague-Dawley rat liver, its presence in ACI liver could provide a ready explanation for the predominance of 4-hydroxy-E2 as a product. The identity of the estradiol 4-hydroxylase in ACI rat liver and the role of this unique reaction in the heightened sensitivity to E2 carcinogenicity remain to be elucidated.

  18. Glutamine synthetase and alanine transaminase expression are decreased in livers of aged vs. young beef cows and GS can be upregulated by 17β-estradiol implants.

    PubMed

    Miles, E D; McBride, B W; Jia, Y; Liao, S F; Boling, J A; Bridges, P J; Matthews, J C

    2015-09-01

    Aged beef cows (≥ 8 yr of age) produce calves with lower birth and weaning weights. In mammals, aging is associated with reduced hepatic expression of glutamine synthetase (GS) and alanine transaminase (ALT), thus impaired hepatic Gln-Glu cycle function. To determine if the relative protein content of GS, ALT, aspartate transaminase (AST), glutamate transporters (EAAC1, GLT-1), and their regulating protein (GTRAP3-18) differed in biopsied liver tissue of (a) aged vs. young (3 to 4 yr old) nonlactating, nongestating Angus cows (Exp. 1 and 2) and (b) aged mixed-breed cows with and without COMPUDOSE (17β-estradiol) ear implants (Exp. 3), Western blot analyses were performed. In Exp. 1, 12 young (3.62 ± 0.01 yr) and 13 aged (10.08 ± 0.42 yr) cows grazed the same mixed forage for 42 d (August-October). In Exp. 2, 12 young (3.36 ± 0.01 yr) and 12 aged (10.38 ± 0.47 yr) cows were individually fed (1.03% of BW) a corn-silage-based diet to maintain BW for 20 d. For both Exp. 1 and 2, the effect of cow age was assessed by ANOVA using the MIXED procedure of SAS. Cow BW did not change ( ≥ 0.17). Hepatic ALT (78% and 61%) and GS (52% and 71%) protein content (Exp. 1 and 2, respectively) was decreased ( ≤ 0.01), whereas GTRAP3-18 (an inhibitor of EAAC1 activity) increased ( ≤ 0.01; 170% and 136%) and AST, GLT-1, and EAAC1 contents did not differ ( ≥ 0.17) in aged vs. young cows. In Exp. 2, free concentrations (nmol/g) of Glu, Ala, Gln, Arg, and Orn in liver homogenates were determined. Aged cows tended to have less ( = 0.10) free Gln (15.0%) than young cows, whereas other AA concentrations did not differ ( 0.26). In Exp. 3, 14 aged (> 10 yr) cows were randomly allotted ( = 7) to sham or COMPUDOSE (25.7 mg of 17β-estradiol) implant treatment (TRT), and had ad libitum access to alfalfa hay for 28 d. Blood and liver biopsies were collected 14 and 28 d after implant treatment. Treatment, time after implant (DAY), and TRT × DAY effects were assessed by ANOVA using

  19. Association of estradiol on expression of melanocortin receptors and their accessory proteins in the liver of chicken (Gallus gallus).

    PubMed

    Ren, Junxiao; Li, Yanmin; Xu, Naiyi; Li, Hong; Li, Cuicui; Han, Ruili; Wang, Yanbin; Li, Zhuanjian; Kang, Xiangtao; Liu, Xiaojun; Tian, Yadong

    2017-01-01

    The melanocortin receptor accessory proteins (MRAP and MRAP2) are small single-pass transmembrane proteins that regulate the biological functions of the melanocortin receptor (MCR) family. MCRs comprise five receptors (MC1R-MC5R) with diverse physiological roles in mammals. Five MCR members and two MRAPs were also predicted in the chicken (Gallus gallus) genome. However, little is known about their expression, regulation and biological functions. In this study, we cloned the MRAP and MRAP2 genes. Sequencing analysis revealed that the functional domains of MRAP and MRAP2 were conserved among species, suggesting that the physiological roles of chicken MRAP and MRAP2 could be similar to their mammalian counterparts. Tissue expression analysis demonstrated that MRAP was expressed in the adrenal gland, liver, spleen, glandular stomach and lungs, while MRAP2 is predominantly expressed in the adrenal gland. All five MCRs were present in the adrenal gland, but showed different expression patterns in other tissues. The MC5R was the only MCR member that was expressed in the chicken liver. The expression levels of MRAP in chicken liver were significantly increased at sexual maturity stage, and were significantly up-regulated (P<0.05) when chickens and chicken primary hepatocytes were treated with 17β-estradiol in vivo and in vitro, respectively; however, expression levels of PPARγ were down-regulated, and no effect on MC5R was observed. Our results suggested that estrogen could stimulate the expression of MRAP in the liver of chicken through inhibiting the expression of transcription regulation factor PPARγ, and MRAP might play its biological role in a different way rather than forming an MRAP/MC2R complex in chicken liver during the egg-laying period. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 17B-Estradiol in Runoff as Affected by Various Poultry Litter Application Strategies

    USDA-ARS?s Scientific Manuscript database

    Runoff of estrogen from land fertilized with poultry litter has recently received increased attention. The objective of this study was to determine the effects of various poultry litter application strategies on 17B-estradiol concentrations in runoff water. Treatments included the effects of 1) al...

  1. Form of supplemental selenium fed to cycling cows affects systemic concentrations of progesterone but not those of estradiol.

    PubMed

    Cerny, Katheryn L; Anderson, Les; Burris, Walter R; Rhoads, Michelle; Matthews, James C; Bridges, Phillip J

    2016-03-15

    In areas where soils are deficient in selenium (Se), dietary supplementation of this trace mineral directly to cattle is recommended. Selenium status affects fertility, and the form of Se supplemented to cows affects tissue-specific gene expression profiles. The objective of this study was to determine whether the form of Se consumed by cows would affect follicular growth and the production of steroids. Thirty-three Angus-cross cows that had ad libitum access of a mineral mix containing 35 ppm of Se in free-choice vitamin-mineral mixes as either inorganic (ISe), organic (OSe), or a 50/50 mix of ISe and OSe (MIX) for 180 days were used. After 170 days of supplementation, all cows were injected with 25-mg PGF2α to induce regression of the CL and then monitored for behavioral estrus (Day 0). From Day 4 to Day 8 after estrus, follicular growth was determined by transrectal ultrasonography. On Day 6, cows were injected with PGF2α (20 then 15 mg, 8-12 hours apart) to induce regression of the developing CL and differentiation of the dominant follicle of the first follicular wave into a preovulatory follicle. On Day 8, 36 hours after PGF2α (20 mg), the contents of the preovulatory follicle were aspirated by ultrasound-guided follicular puncture. Blood collected on Days 6 and 8 and follicular fluid collected on Day 8 was analyzed for concentrations of progesterone and estradiol. Form of Se supplemented to cows affected (P = 0.04) the systemic concentration of progesterone on Day 6, but not on Day 8. Form of Se did not affect the systemic concentration of estradiol on Day 6 or Day 8. Form of Se tended to affect (P = 0.07) the concentration of progesterone, but not that of estradiol, in the follicular fluid. Form of Se did not affect diameter of the dominant ovarian follicle on Days 4 to 6, but tended to affect (P = 0.08) the diameter of the preovulatory follicle on Day 8. Our results suggest that form of Se fed to cows affects the production of progesterone but not that

  2. Biodegradable estradiol microspheres do not affect uterine involution or characteristics of postpartum estrus in mares.

    PubMed

    Arrott, C; Macpherson, M; Blanchard, T; Varner, D; Thompson, J; Simpson, B; Bruemmer, J; Vogelsang, S; Fernandez, M; Fleet, T; Burns, P

    1994-08-01

    Quarterhorse mares were used to investigate effects of estradiol-17beta on uterine involution, duration of estrus, interval to ovulation, and fertility achieved by breeding on the first postpartum estrus. On the day of foaling, mares were injected with biodegradable poly (DL-lactide) microspheres containing either 100 mg estradiol-17beta (25 mares) or no drug (27 mares). The treatment period was considered to last for 12 to 15 d. Estrus was determined by teasing mares (n=16) with a stallion. Ovulation was detected by transrectal ultrasonographic examination of ovaries (n=48). On Days 6, 11 and 16 post partum, transrectal ultrasonography was used to measure cross-sectional diameters of the uterine body, uterine horns, and fluid within the uterine lumen (n=28). Uteri were swabbed for bacteriologic culture, and uterine biopsies were obtained from the previously gravid uterine horn on Days 11 and 16 post partum, for assessment of endometritis and morphometric analysis of endometrial histioarchitecture (n=19). Twenty-two mares were bred on foal-heat, and pregnancy was determined by transrectal ultrasonography on 14 to 16 and 30 to 35 d after breeding. With only one exception (diameter of previously gravid uterine horn on Day 11), mean values for all measures of uterine involution did not differ between treatment groups (P > 0.05). No differences were detected between treatment group means for length of estrus or interval to ovulation (P > 0.05). No differences were detected between treatment group liklihoods for recovery of potential bacterial pathogens, presence of endometritis, or presence of intrauterine fluid at 11 or 16 d post partum (P > 0.05). Pregnancy rate of mares treated with estradiol (5 11 ; 45%) was not different from that of control mares (9 11 ; 82%; P > 0.05). Estradiol treatment did not hasten uterine involution, increase duration of estrus, delay ovulation, or increase fertility in these postpartum mares.

  3. Estradiol and endocrine disrupting compounds adversely affect development of sea urchin embryos at environmentally relevant concentrations.

    PubMed

    Roepke, Troy A; Snyder, Mark J; Cherr, Gary N

    2005-01-26

    Environmental endocrine disrupting compounds (EDCs) are a wide variety of chemicals that typically exert effects, either directly or indirectly, through receptor-mediated processes, thus mimicking endogenous hormones and/or inhibiting normal hormone activities and metabolism. Little is known about the effects of EDCs on echinoderm physiology, reproduction and development. We exposed developing sea urchin embryos (Strongylocentrotus purpuratus and Lytechinus anamesus) to two known EDCs (4-octylphenol (OCT), bisphenol A (BisA)) and to natural and synthetic reproductive hormones (17beta-estradiol (E2), estrone (E1), estriol (E3), progesterone (P4) and 17alpha-ethynylestradiol (EE2)). In addition, we studied two non-estrogenic EDCs, tributyltin (TBT) and o,p-DDD. Successful development to the pluteus larval stage (96 h post-fertilization) was used to define EDC concentration-response relationships. The order of compound potency based on EC50 values for a reduction in normal development was as follows: TBT(L. anamesus)>OCT>TBT(S. purpuratus)>E2>EE2>DDD>BisA>P4>E1>E3. The effect of TBT was pronounced even at concentrations substantially lower than those commonly reported in heavily contaminated areas, but the response was significantly different in the two model species. Sea urchin embryos were generally more sensitive to estrogenic EDCs and TBT than most other invertebrate larvae. Stage-specific exposure experiments were conducted to determine the most sensitive developmental periods using blastula, gastrula and post-gastrula (pluteus) stages. The stage most sensitive to E2, OCT and TBT was the blastula stage with less overall sensitivity in the gastrula stage, regardless of concentration. Selective estrogen receptor modulators (SERMs) were added to the experiments individually and in combination with estrogenic EDCs to interfere with potential receptor-mediated actions. Tamoxifen, a partial ER agonist, alone inhibited development at concentrations as low as 0.02 ng

  4. The Role of Hippocampal Estradiol Receptor-α in a Perimenopausal Affective Disorders-Like Rat Model and Attenuating of Anxiety by Electroacupuncture

    PubMed Central

    Huang, Yongheng; Ma, Shulan

    2016-01-01

    Hormone replacement therapy is the principal treatment for perimenopausal affective disorders which can cause severe side effects. The present study compared the effects of electroacupuncture (EA) and estradiol treatment on perimenopausal affective disorders at the behavioral and cellular levels. In this randomized experimental in vivo study, adult female rats were divided into intact, ovariectomy, chronic unpredictable stress (CUS), and ovariectomy and CUS combination groups. After week 6, all groups were subdivided to three subgroups of control, EA, and estradiol treatment. The behavioral parameters in the open field and the elevated plus maze tests were assessed before and after treatments. Alterations of serum steroid hormones and changes of estradiol receptor-α (ER-α) immunofluorescence neurons in the hippocampus sections were evaluated. EA treatment caused more antianxiety effects than estradiol treatment in CUS group (P < 0.05). Notably, estradiol and EA treatments had better significant behavioral effects when the models were not estrogen-deficient. Importantly, within each group, compared to the control group, the numbers of ER-α-positive neurons were significantly larger in EA subgroups. Therefore, EA had antianxiety effects on perimenopausal affective disorders caused by CUS but not by estrogen deficiency and upregulation of hippocampus ER-α neurons may contribute to its mechanism of action. PMID:28044085

  5. Relationship between estradiol-17 beta seasonal profile and annual vitellogenin content of liver, fat body, plasma, and ovary in the frog (Rana esculenta).

    PubMed

    Varriale, B; Pierantoni, R; Di Matteo, L; Minucci, S; Milone, M; Chieffi, G

    1988-03-01

    The seasonal plasma estradiol-17 beta (E2-17 beta) profile and annual vitellogenin content of liver, fat body, plasma, and ovary were investigated in Rana esculenta. Concomitant with the increase in E2-17 beta, vitellogenin peaked in liver, plasma, and ovary during autumn and winter, while it remained at a relatively high concentration in fat body during spring. In vitro experiments showed that E2-17 beta (10(-9) M) is ineffective in inducing vitellogenin production in fat body, but is effective in inducing vitellogenin production in liver. As fat bodies do not produce the vitellogenin they contain, we suggest that fat bodies are involved in the transfer of vitellogenin to the ovary.

  6. Contraceptive Use Affects Overall Olfactory Performance: Investigation of Estradiol Dosage and Duration of Intake

    PubMed Central

    Ohrenberger, Iris

    2016-01-01

    The influence of female sex steroids on cognitive performance and sensory perception has been investigated for decades. However, previous research that studied olfaction revealed inconsistent results. The main aim of this study was to investigate the effects of different ethinyl estradiol (EE) concentrations of oral contraceptives and duration of intake on olfactory function. Forty-two healthy women, with regular intake of either high or low EE dosage over at least one year and up to 15 years participated in this study. Results revealed a significant concordance between a priori categorization in the two groups with high and low EE dosage and data-driven hierarchical clustering (p = 0.008). Furthermore, significantly higher olfactory performance was observed in women using low-dose products compared to women using high-dosed products (p = 0.019). These findings indicate different effects of pill use with regard to EE concentration. We therefore strongly recommend the acquisition of information about EE dosage of oral contraceptives to reduce potential confounding factors when investigating sensory systems. PMID:28002464

  7. Peroxisome proliferator activated receptor ligands affect progesterone and 17β-estradiol secretion by porcine corpus luteum during early pregnancy.

    PubMed

    Kurzynska, A; Bogacki, M; Chojnowska, K; Bogacka, I

    2014-10-01

    In the present study we investigated the effect of peroxisome proliferator activated receptor (PPAR) ligands on progesterone (P4) and 17β-estradiol (E2) secretion and 3b-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3β-HSD) mRNA abundance in porcine corpora lutea (CL) collected on days 10-12 and 14-16 of the estrous cycle or pregnancy. The PPAR agonists reduced P4 secretion by the CL during pregnancy whereas they were ineffective during the estrous cycle. An inhibitory effect of WY-14643 (PPARα agonist) on P4 release was noted on days 14-16 of pregnancy. The treatment of the CL with L-165,045 (PPARβ agonist) diminished P4 release by the tissue during both stages of pregnancy. A natural PPARγ agonist, PGJ2, reduced P4 release on days 14-16 or days 10-12 of pregnancy, respectively. Rosiglitazone (PPARγ agonist) inhibited P4 secretion by the CL on days 10-12 of pregnancy. In turn, PPARα ligands effect on E2 release was differential. While PPARγ activator diminished E2 secretion by the CL explants during all tested stages of the estrous cycle and pregnancy, PPARβ ligands did not induce any change in E2 level. In turn, PPARβ agonist reduced E2 release by the tissue during both stages of pregnancy but did not affect the secretion during the estrous cycle. In the present study there was a lack of PPAR ligands effect on 3β-HSD mRNA abundance. In summary, the results suggest that PPARs are involved in the regulation of progesterone and 17β-estradiol release by porcine CL. Porcine CL indicates a different receptivity to PPAR ligands depending on the reproductive status of animals.

  8. Neonatal exposure to estradiol decreases hypothalamic allopregnanolone concentrations and alters agonistic and sexual but not affective behavior in adult female rats.

    PubMed

    Berretti, R; Santoru, F; Locci, A; Sogliano, C; Calza, A; Choleris, E; Porcu, P; Concas, A

    2014-02-01

    Exposure of developing female rats to estradiol during the perinatal period induced long-lasting dysregulation of gonadal axis and decreased cerebrocortical and plasma concentrations of allopregnanolone. We have now examined the effects of neonatal estradiol administration in female rats on hypothalamic allopregnanolone concentrations and on exploratory, affective, agonistic and sexual behaviors as well as social learning. A single administration of β-estradiol 3-benzoate (EB, 10μg) on the day of birth resulted in a delay of vaginal opening, acyclicity and ovarian failure. These alterations were associated with a significant decrease in the concentrations of allopregnanolone in the hypothalamus at 21 and 60days, but not at 7days, after birth. Neonatal administration of EB also increased agonistic behaviors in adult rats, such as dominant behaviors and following of an ovariectomized intruder, while living attacks unaffected. EB-treated rats showed also an increase in anogenital investigation, associated with a drastic reduction in spontaneous and induced female sexual behaviors (receptivity and proceptivity). In contrast, neonatal administration of EB did not affect locomotor activity, anxiety- and mood-related behaviors, the social transmission of flavor preferences, and seizures sensitivity. These effects of estradiol suggest that it plays a major role in regulation of both the abundance of allopregnanolone and the expression of agonistic and sexual behaviors, while failing to influence affective behaviors and social learning. Thus, the pronounced and persistent decrease in hypothalamic allopregnanolone concentration may be related to the manifestation of agonistic and sexual behaviors.

  9. Experimentally induced "fatty liver syndrome" condition in laying hens.

    PubMed

    Harms, R H; Roland, D A; Simpson, C F

    1977-03-01

    Two experiments were conducted with aged laying hens to determine the influence of feeding 5,000 p.p.m. of iodine as potassium iodine (KI) and/or injecting 12 mg. of estradiol upon fat accumulation in the liver and serum cholesterol levels. The KI was fed for 8 days before making liver and blood determinations, and the estradiol was injected 3 days prior to making the determinations. The feeding of KI or injection of estradiol resulted in significantly increased liver weight. When the two treatments were combined a further significant increase in liver weights was obtained. The percent of fat in the liver was significantly increased by the injection of estradiol. However, the feeding of KI in the presence or absence of estradiol did not affect the percentage of fat in the liver. Neither of the treatments significantly affected the fatty acid composition of the liver fat. Feeding of KI or injection of estradiol significantly increased total serum cholesterol levels. When the two treatments were combined a further increase in serum cholesterol level was observed. Histological changes of the livers of hens treated with KI and estradiol were similar to those previously described for the "fatty liver syndrome."

  10. Estradiol and GPER Activation Differentially Affect Cell Proliferation but Not GPER Expression in the Hippocampus of Adult Female Rats.

    PubMed

    Duarte-Guterman, Paula; Lieblich, Stephanie E; Chow, Carmen; Galea, Liisa A M

    2015-01-01

    Estradiol increases cell proliferation in the dentate gyrus of the female rodent but it is not known whether the G protein-coupled estrogen receptor (GPER), a membrane receptor, is involved in this process, nor whether there are regional differences in estradiol's effects on cell proliferation. Thus, we investigated whether estradiol exerts its effects on cell proliferation in the dorsal and ventral dentate gyrus through GPER, using the GPER agonist, G1, and antagonist, G15. Ovariectomized adult female rats received a single injection of either: 17β-estradiol (10 μg), G1 (0.1, 5, 10 μg), G15 (40 μg), G15 and estradiol, or vehicle (oil, DMSO, or oil+DMSO). After 30 min, animals received an injection of bromodeoxyuridine (BrdU) and were perfused 24 h later. Acute treatment with estradiol increased, while the GPER agonist G1 (5 μg) decreased, the number of BrdU+ cells in the dentate gyrus relative to controls. The GPER antagonist, G15 increased the number of BrdU+ cells relative to control in the dorsal region and decreased the number of BrdU+ cells in the ventral region. However, G15 treatment in conjunction with estradiol partially eliminated the estradiol-induced increase in cell proliferation in the dorsal dentate gyrus. Furthermore, G1 decreased the expression of GPER in the dentate gyrus but not the CA1 and CA3 regions of the hippocampus. In summary, we found that activation of GPER decreased cell proliferation and GPER expression in the dentate gyrus of young female rats, presenting a potential and novel estrogen-independent role for this receptor in the adult hippocampus.

  11. Dietary starch types affect liver nutrient metabolism of finishing pigs.

    PubMed

    Xie, Chen; Li, Yanjiao; Li, Jiaolong; Zhang, Lin; Zhou, Guanghong; Gao, Feng

    2017-09-01

    This study aimed to evaluate the effect of different starch types on liver nutrient metabolism of finishing pigs. In all ninety barrows were randomly allocated to three diets with five replicates of six pigs, containing purified waxy maize starch (WMS), non-waxy maize starch (NMS) and pea starch (PS) (the amylose to amylopectin ratios were 0·07, 0·19 and 0·28, respectively). After 28 d of treatments, two per pen (close to the average body weight of the pen) were weighed individually, slaughtered and liver samples were collected. Compared with the WMS diet, the PS diet decreased the activities of glycogen phosphorylase, phosphoenolpyruvate carboxykinase and the expression of phosphoenolpyruvate carboxykinase 1 in liver (P0·05). Compared with the WMS diet, the PS diet reduced the expressions of glutamate dehydrogenase and carbamoyl phosphate synthetase 1 in liver (P<0·05). PS diet decreased the expression of the insulin receptor, and increased the expressions of mammalian target of rapamycin complex 1 and ribosomal protein S6 kinase β-1 in liver compared with the WMS diet (P<0·05). These findings indicated that the diet with higher amylose content could down-regulate gluconeogenesis, and cause less fat deposition and more protein deposition by affecting the insulin/PI3K/protein kinase B signalling pathway in liver of finishing pigs.

  12. Antisense oligodeoxynucleotides for estrogen receptor-beta and alpha attenuate estradiol's modulation of affective and sexual behavior, respectively.

    PubMed

    Walf, Alicia A; Ciriza, Iratxe; Garcia-Segura, Luis Miguel; Frye, Cheryl A

    2008-01-01

    Estradiol (E(2)) modulates affective and socio-sexual behavior of female rodents. E(2)'s functional effects may involve actions through alpha and beta isoforms of estrogen receptor (ERs). The importance of E(2)'s actions at these isoforms for anxiety (open field, elevated plus maze), depression (forced swim test), and sexual behavior (lordosis) was investigated using an antisense oligonucleotide (AS-ODN) strategy. If ERbeta is required for anti-anxiety and antidepressant-like effects, and ERalpha is required for sexual receptivity, of E(2), then intracerebroventricular administration of AS-ODNs against these ERs should attenuate these effects and reduce immunoreactivity of ERs in brain regions that mediate these behaviors, such as the hippocampus and ventral medial hypothalamus (VMH). Ovariectomized rats were primed with 17beta-E(2) (10 microg) 48 h before testing (hour 0). At hours 0, 24, and 47.5, rats were infused with saline vehicle, scrambled control AS-ODNs, or AS-ODNs targeted against ERalpha and/or ERbeta, and were tested at hour 48. Rats infused with ERbeta AS-ODNs, alone, or with ERalpha AS-ODNs had significantly decreased open field central entries, decreased plus maze open arm time and entries, increased time spent immobile, and decreased time spent swimming in the forced swim test, and decreased ERbeta immunoreactivity in the brain than did rats administered ERalpha AS-ODNs, vehicle, or scrambled AS-ODNs. Rats that were administered ERalpha AS-ODNs, alone, or with ERbeta AS-ODNs had significantly decreased lordosis and decreased ERalpha immunoreactivity in the brain compared to rats administered ERbeta AS-ODNs, vehicle, or scrambled AS-ODNs. Thus, ERbeta and ERalpha may be required for E(2)'s modulation of affective and sexual behavior, respectively.

  13. Estradiol and GPER Activation Differentially Affect Cell Proliferation but Not GPER Expression in the Hippocampus of Adult Female Rats

    PubMed Central

    Duarte-Guterman, Paula; Lieblich, Stephanie E.; Chow, Carmen; Galea, Liisa A. M.

    2015-01-01

    Estradiol increases cell proliferation in the dentate gyrus of the female rodent but it is not known whether the G protein-coupled estrogen receptor (GPER), a membrane receptor, is involved in this process, nor whether there are regional differences in estradiol’s effects on cell proliferation. Thus, we investigated whether estradiol exerts its effects on cell proliferation in the dorsal and ventral dentate gyrus through GPER, using the GPER agonist, G1, and antagonist, G15. Ovariectomized adult female rats received a single injection of either: 17β-estradiol (10 μg), G1 (0.1, 5, 10 μg), G15 (40 μg), G15 and estradiol, or vehicle (oil, DMSO, or oil+DMSO). After 30 min, animals received an injection of bromodeoxyuridine (BrdU) and were perfused 24 h later. Acute treatment with estradiol increased, while the GPER agonist G1 (5 μg) decreased, the number of BrdU+ cells in the dentate gyrus relative to controls. The GPER antagonist, G15 increased the number of BrdU+ cells relative to control in the dorsal region and decreased the number of BrdU+ cells in the ventral region. However, G15 treatment in conjunction with estradiol partially eliminated the estradiol-induced increase in cell proliferation in the dorsal dentate gyrus. Furthermore, G1 decreased the expression of GPER in the dentate gyrus but not the CA1 and CA3 regions of the hippocampus. In summary, we found that activation of GPER decreased cell proliferation and GPER expression in the dentate gyrus of young female rats, presenting a potential and novel estrogen-independent role for this receptor in the adult hippocampus. PMID:26075609

  14. EFFECT OF 17B-ESTRADIOL, O,P'-DDT, OCTYLPHENOL AND P,P'-DDE ON GONADAL DEVELOPMENT AND LIVER AND KIDNEY PATHOLOGY IN JUVENILE MALE SUMMER FLOUNDER (PARALICHTYS DENTATUS)

    EPA Science Inventory

    The intent of this study was to compare histopathologically the effect of 17 -estradiol (E2), o,p' DDT, octylphenol and p,p' DDE on gonadal development and liver and kidney condition in sexually immature (juvenile) summer flounder (Paralichthys dentatus). The dorsal sinus of 2-...

  15. EFFECT OF 17B-ESTRADIOL, O,P'-DDT, OCTYLPHENOL AND P,P'-DDE ON GONADAL DEVELOPMENT AND LIVER AND KIDNEY PATHOLOGY IN JUVENILE MALE SUMMER FLOUNDER (PARALICHTYS DENTATUS)

    EPA Science Inventory

    The intent of this study was to compare histopathologically the effect of 17 -estradiol (E2), o,p' DDT, octylphenol and p,p' DDE on gonadal development and liver and kidney condition in sexually immature (juvenile) summer flounder (Paralichthys dentatus). The dorsal sinus of 2-...

  16. Acute estradiol treatment affects the expression of cocaine-induced conditioned place preference in ovariectomized female rats.

    PubMed

    Bobzean, Samara A M; Dennis, Torry S; Perrotti, Linda I

    2014-04-01

    Women and female rodents are more responsive to the subjective effects of psychostimulant drugs of abuse compared to males. A growing body of literature supports a role for estradiol as a mechanism underlying these sex differences. However, little is known about the influence of acute elevations in levels of estradiol on drug conditioned behaviors. The aim of the present study was to evaluate the influence of an acute increase in systemic estradiol levels on the expression of cocaine conditioned place preference (CPP). Using a six day conditioning procedure, ovariectomized (OVX) female rats were conditioned with one of four doses of cocaine (2.5, 5, 10, or 15mg/kg) to associate one of two large chambers of a CPP apparatus with cocaine or saline. Thirty minutes prior to the start of the CPP preference test, rats were pretreated with either 5μg estradiol benzoate (EB) or peanut oil (PO). PO-treated rats expressed a significant preference for only the mid-range conditioning doses of cocaine (5 and 10mg/kg). However, acute EB treatment resulted in a rightward shift in the cocaine dose-response curve; rats demonstrated a significant preference at only the moderate and high conditioning doses of cocaine (10 and 15mg/kg). These findings demonstrate that acute elevations in estradiol may dampen the expression of conditioned responses to cocaine's secondary rewards at lower conditioning doses of the drug and facilitate CPP at higher doses while estradiol deficiency decreases the threshold dose of cocaine necessary to induce CPP.

  17. 17α-Ethinyl estradiol affects anxiety and shoaling behavior in adult male zebra fish (Danio rerio).

    PubMed

    Reyhanian, Nasim; Volkova, Kristina; Hallgren, Stefan; Bollner, Tomas; Olsson, Per-Erik; Olsén, Håkan; Hällström, Inger Porsch

    2011-09-01

    Ethinyl estradiol is a potent endocrine disrupting compound in fish and ubiquitously present in the aquatic environment. In this study, we exposed adult zebra fish (Danio rerio) males to 0, 5 or 25 ng Ethinyl estradiol/L for 14 days and analyzed the effects on non-reproductive behavior. Effects of treatment of the exposed males was shown by vitellogenin induction, while brain aromatase (CYP 19B) activity was not significantly altered. Both concentrations of Ethinyl estradiol significantly altered the behavior in the Novel tank test, where anxiety is determined as the tendency to stay at the bottom when introduced into an unfamiliar environment. The effects were, however, opposite for the two concentrations. Fish that were exposed to 5 ng/L had longer latency before upswim, fewer transitions to the upper half and shorter total time spent in the upper half compared with control fish, while 25 ng Ethinyl estradiol treatment resulted in shorter latency and more and longer visits to the upper half. The swimming activity of 25, but not 5 ng-exposed fish were slightly but significantly reduced, and these fish tended to spend a lot of time at the surface. We also studied the shoaling behavior as the tendency to leave a shoal of littermates trapped behind a Plexiglas barrier at one end of the test tank. The fish treated with Ethinyl estradiol had significantly longer latency before leaving shoal mates and left the shoal fewer times. Further, the fish exposed to 5 ng/L also spent significantly less time away from shoal than control fish. Fertilization frequency was higher in males exposed to 5 ng/L Ethinyl estradiol when compared with control males, while no spawning was observed after treatment with 25 ng/L. The testes from both treatment groups contained a normal distribution of spermatogenesis stages, and no abnormality in testis morphology could be observed. In conclusion, we have observed effects on two behaviors not related to reproduction in zebra fish males after

  18. Gender-related effects of 17-{beta}-estradiol and B-hexachlorocyclohexane on liver tumor formation in medaka (Oryzias latipes)

    SciTech Connect

    Cooke, J.B.; Hinton, D.E.

    1994-12-31

    When medaka were acutely exposed to diethylnitrosamine (DEN), greater incidence of hepatocarcinoma was seen in female versus male fish. This is possibly related to elevated female endogenous estrogens, which increase liver weight and production of vitellogenin. To examine roles of estrogens in tumor modulation, 21-day old medaka were exposed to DEN (200 ppm for 24 hr.), then fed purified diets containing the estrogenic compound {beta}-hexachlorocyclohexane ({beta}-HCH) or 17-{beta}estradiol (E2) for 6 months. Incidences of basophilic preneoplastic foci of cellular alteration in females receiving DEN and 0.01, 0.1, or 1.0 ppm E2 were three times the incidences in similarly-treated males. Also, incidences of basophilic foci in DEN + 0.1 ppm E2 males were significantly increased over DEN-only males and were equal to incidences in DEN-only females. Liver weights and hepatosomatic indices of males given 0.1 ppm E2 were not significantly different than females fed control diet. Females fed 0.01-10.0 ppm {beta}-HCH after DEN had 4--5 times greater incidences of basophilic foci as males. Gender-related effects on kinetics of growth rates and volumes of foci are being examined.

  19. Gastric 17β-estradiol in portal vein and liver Esr1 make a circadian rhythm in systemic circulation in male rats.

    PubMed

    Kobayashi, Hiroto; Yoshida, Saori; Sun, Ying-Jie; Shirasawa, Nobuyuki; Naito, Akira

    2016-08-01

    The hemodynamics of 17β-estradiol (E2) synthesized and secreted from the stomach has been revealed gradually. This study aimed to clarify the circadian rhythm of E2 synthesis and secretion in the stomach, and the relationship between the expression of hepatic estrogen receptor (ER) α and serum E2 levels in systemic circulation. Wistar male rats were maintained in a room with a 12-h light and 12-h dark cycle (lights on from 0700 to 1900 h), and were sacrificed at every 4-hour interval starting at 0800 h. The results showed that the expression of gastric Cyp19a1 was higher in nighttime than in daytime, and that the portal venous E2 level was 2.2 times higher at 2400 h than that at 1200 h. The arterial E2 level was also the highest at 2400 h, and showed an apparent circadian rhythm positively correlated with portal venous E2 levels. Conversely, the expression of liver Esr1 peaked at 1200 h and turned to decrement at 2400 h. The population of immunoreactive nuclei with ERα antibody decreased at 2400 h compared with that at 1200 h. The regression analysis showed that the liver Esr1 mRNA was negatively correlated to portal venous and arterial E2 levels. It could be concluded that the circadian rhythm of the systemic E2 level depended both on the amounts of gastric E2 in the portal vein and on the Esr1 expression in the liver.

  20. Effects of estradiol benzoate on 5'-iodothyronine deiodinase activities in female rat anterior pituitary gland, liver and thyroid gland.

    PubMed

    Lisbôa, P C; Curty, F H; Moreira, R M; Pazos-Moura, C C

    1997-12-01

    There is little information on the possible effects of estrogen on the activity of 5'-deiodinase (5'-ID), an enzyme responsible for the generation of T3, the biologically active thyroid hormone. In the present study, anterior pituitary sonicates or hepatic and thyroid microsomes from ovariectomized (OVX) rats treated or not with estradiol benzoate (EB, 0.7 or 14 micrograms/100 g body weight, s.c., for 10 days) were assayed for type I 5'-ID (5'-ID-I) and type II 5'-ID (5'-ID-II, only in pituitary) activities. The 5'-ID activity was evaluated by the release of 125I from deiodinated 125I rT3, using specific assay conditions for type I or type II. Serum TSH and free T3 and free T4 were measured by radioimmunoassay. OVX alone induced a reduction in pituitary 5'-ID-I (control = 723.7 +/- 67.9 vs OVX = 413.9 +/- 26.9; P < 0.05), while the EB-treated OVX group showed activity similar to that of the normal group. Thyroid 5'-ID-I showed the same pattern of changes, but these changes were not statistically significant. Pituitary and hepatic 5'-ID-II did not show major alterations. The treatment with the higher EB dose (14 micrograms), contrary to the results obtained with the lower dose, had no effect on the reduced pituitary 5'-ID-I of OVX rats. However, it induced an important increment of 5'-ID-I in the thyroid gland (0.8 times higher than that of the normal group: control = 131.9 +/- 23.7 vs OVX + EB 14 micrograms = 248.0 +/- 31.2; P < 0.05), which is associated with increased serum TSH (0.6-fold vs OVX, P < 0.05) but normal serum free T3 and free T4. The data suggest that estrogen is a physiological stimulator of anterior pituitary 5'-ID-I and a potent stimulator of the thyroid enzyme when employed at high doses.

  1. Estradiol differently affects melanin synthesis of malignant and normal melanocytes: a relationship with clock and clock-controlled genes.

    PubMed

    Poletini, Maristela Oliveira; de Assis, Leonardo Vinicius Monteiro; Moraes, Maria Nathalia; Castrucci, Ana Maria de Lauro

    2016-10-01

    Melanin production within melanocytes is regulated, among others, by estradiol, whose effects on melanogenesis are still not completely elucidated. Here we show that although 10(-7) M 17β-estradiol (E2) increased tyrosinase mRNA levels in B16-F10 malignant melanocytes, there was a transient decrease and abolishment of the temporal variation of melanin content. Both parameters were much higher in the malignant than in normal Melan-a cells. Considering that silencing clock machinery in human melanocytes increases melanogenesis, we investigated clock gene expression in those cell lines. Except for Melan-a Bmal1 and B16-F10 Per2 expression of control cells, Per1, Per2, and Bmal1 expression increased independently of cell type or E2 treatment after 24 h. However, melanoma cells showed a marked increase in Per1 and Bma11 expression in response to E2 at the same time points, what may rule out E2 as a synchronizer agent since the expression of those genes were not in antiphase. Next, we investigated the expression of Xpa, a clock-controlled gene, which in Melan-a cells, peaked at 18 h, and E2 treatment shifted this peak to 24 h, whereas B16-F10 Xpa expression peaked at 24 h in both control and E2 group, and it was higher compared to Melan-a cells in both groups. Therefore, malignant and normal melanocytes display profound differences on core elements of the local clock, and how they respond to E2, what is most probably determinant of the differences seen on melanin synthesis and Tyrosinase and Xpa expression. Understanding these processes at the molecular level could bring new strategies to treat melanoma.

  2. Blood Test: Estradiol

    MedlinePlus

    ... 2-Year-Old Blood Test: Estradiol KidsHealth ... measures the level of the hormone estradiol in the bloodstream. Estradiol plays an important role in sexual development: It's the most important form of the hormone ...

  3. High-affinity binding of (/sup 3/H)estradiol-17 beta by an estrogen receptor in the liver of the turtle

    SciTech Connect

    Ho, S.M.; Fehrer, S.; Yu, M.; Liang, L.C.; Press, D.

    1988-06-01

    Specific (3H)estradiol-17 beta ((3H)E2) binding activity (EBA) with characteristics of an estrogen receptor (ER) was demonstrated in cytosols and nuclear extracts of the female turtle, Chrysemys picta. Three different receptor assays (dextran-coated charcoal assay, hydroxylapatite batch procedure, and DNA-cellulose chromatography) were evaluated in terms of their applicability in analyzing large numbers of samples. For the measurement of cytosolic EBA, the hydroxylapatite batch procedure was found to be the most reliable assay. On the other hand, the dextran-coated charcoal assay was found to be the most appropriate method for the measurement of nuclear EBA. Turtle hepatic EBA binds (3H)E2 with high affinity (cytosolic, 17.4 +/- 2.8 X 10(9) M-1; nuclear, 17.7 +/- 1.9 X 10(9) M-1), limited capacity (cytosolic, 133.7 +/- 4.6 fmol/g tissue; nuclear, 81.1 +/- 9.0 fmol/g tissue), and strict steroid specificity. The EBA bound natural estrogens (E2, estrone, estriol) as well as the nonsteroidal estrogen, diethylstilbestrol, but exhibited little affinity for androgens, progesterone, or corticosterone. The turtle hepatic EBA resembled mammalian and avian ERs in terms of binding characteristics; however, unlike mammalian and avian ERs it was shown to be heat-labile. Incubation at 30 degrees caused rapid loss of (3H)E2 binding activity in both cytosolic and nuclear fractions. The exchange between (3H)E2 and the endogenously bound estrogen was slow at 4 and 15 degrees, but the exchange process was facilitated in the presence of the chaotropic salt, NaSCN. Establishment of quantitation methods for both cytosolic and nuclear forms of EBA will enable future investigation of the mechanism and regulation of estrogen action in the liver of this turtle species.

  4. Common 677C-->T mutation of the 5,10-methylenetetrahydrofolate reductase gene affects follicular estradiol synthesis.

    PubMed

    Hecht, Stephanie; Pavlik, Roman; Lohse, Peter; Noss, Ulrich; Friese, Klaus; Thaler, Christian J

    2009-01-01

    To investigate the influence of the 5,10-methylenetetrahydrofolate reductase 677C-->T mutation on the E(2) synthesis in human granulosa cells (GCs). In vitro cell culture study. Research laboratory of a university hospital. Follicular fluids (n = 139) and GCs (n = 66) were obtained from patients undergoing controlled ovarian hyperstimulation for IVF with or without ICSI. Granulosa cells were cultured for a total of 5 days. On day 3, the cells either were stimulated with recombinant (r-) FSH or r-LH (80 IU/L for 48 h) or were sham stimulated. Estradiol and protein content were measured in the pooled follicular fluids of each individual. At the end of each GC-culturing period, the concentrations of E(2) were measured in the supernatants of triplicate cultures by immunoassays. The 5,10-methylenetetrahydrofolate reductase 677C-->T genotype was determined by RFLP analysis. The E(2)-protein ratio of homozygous T/T carriers was significantly lower compared with that of homozygous C/C individuals. Furthermore, basal and r-FSH- as well as r-LH-stimulated E(2) synthesis of GC obtained from homozygous T/T patients was significantly reduced, compared with GC from heterozygous C/T and homozygous C/C subjects. Decreased E(2) in follicular fluid and decreased E(2) synthesis of GC from homozygous T/T individuals suggest that reduced follicular E(2) is a result of impaired E(2) production of human GC.

  5. Deficiency of sex hormones does not affect 17-ß-estradiol-induced coronary vasodilation in the isolated rat heart.

    PubMed

    Santos, R L; Lima, J T; Rouver, W N; Moysés, M R

    2016-01-01

    The relaxation of coronary arteries by estrogens in the coronary vascular beds of naive and hypertensive rats has been well described. However, little is known about this action in gonadectomized rats. We investigated the effect of 17-ß-estradiol (E2) in coronary arteries from gonadectomized rats, as well as the contributions of endothelium-derived factors and potassium channels. Eight-week-old female and male Wistar rats weighing 220-300 g were divided into sham-operated and gonadectomized groups (n=9-12 animals per group). The baseline coronary perfusion pressure (CPP) was determined, and the vasoactive effects of 10 μM E2 were assessed by bolus administration before and after endothelium denudation or by perfusion with NG-nitro-L-arginine methyl ester (L-NAME), indomethacin, clotrimazole, L-NAME plus indomethacin, L-NAME plus clotrimazole or tetraethylammonium (TEA). The CPP differed significantly between the female and sham-operated male animals. Gonadectomy reduced the CPP only in female rats. Differences in E2-induced relaxation were observed between the female and male animals, but male castration did not alter this response. For both sexes, the relaxation response to E2 was, at least partly, endothelium-dependent. The response to E2 was reduced only in the sham-operated female rats treated with L-NAME. However, in the presence of indomethacin, clotrimazole, L-NAME plus indomethacin or L-NAME plus clotrimazole, or TEA, the E2 response was significantly reduced in all groups. These results highlight the importance of prostacyclin, endothelium-derived hyperpolarizing factor, and potassium channels in the relaxation response of coronary arteries to E2 in all groups, whereas nitric oxide may have had an important role only in the sham-operated female group.

  6. Sitagliptin, a dipeptidyl peptidase-4 inhibitor, does not affect the pharmacokinetics of ethinyl estradiol or norethindrone in healthy female subjects.

    PubMed

    Migoya, Elizabeth; Larson, Patrick; Bergman, Arthur; Miller, Jutta; Johnson-Levonas, Amy O; Lasseter, Kenneth C; Wagner, John A

    2011-09-01

    Sitagliptin is a dipeptidyl peptidase-IV (DPP-4) inhibitor used for the treatment of patients with type 2 diabetes mellitus. This randomized, placebo-controlled, 2-period, crossover study evaluated the effect of sitagliptin on the pharmacokinetics of 17 α-ethinyl estradiol (EE(2)) and norethindrone (NET) in healthy female subjects who were receiving oral contraceptives for >3 months prior to enrollment. A total of 18 subjects with normal menstrual cycles received the oral contraceptive pill ORTHO-NOVUM(®) 7/7/7 on days 1 to 28 for 2 successive cycles, and on days 1 to 21 were randomly assigned to receive sitagliptin 200 mg/day (2 × 100 mg tablets) or placebo using a computer-generated allocation schedule. Blood samples for determination of plasma EE(2) and NET concentrations were collected predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours postdose on day 20 or 21 of each treatment period. The GMRs (90% confidence interval [CI]) for the AUC(0-24 hr) of EE(2) and NET were 0.99 (0.93, 1.06) and 1.03 (0.97, 1.09), respectively, and for C(max) were 0.97 (0.86, 1.10) and 0.98 (0.89, 1.07), respectively. The coadministration of sitagliptin 200 mg/day with an oral contraceptive for 21 days did not lead to clinically meaningful alterations in the pharmacokinetics of EE(2) and NET.

  7. Quantitative Trait Loci Affecting Liver Fat Content in Mice

    PubMed Central

    Minkina, Olga; Cheverud, James M.; Fawcett, Gloria; Semenkovich, Clay F.; Kenney-Hunt, Jane P.

    2012-01-01

    Nonalcoholic fatty liver disease, a condition in which excess fat accumulates in the liver, is strongly associated with the metabolic syndrome, including obesity and other related conditions. This disease has the potential to progress from steatosis to steatohepatitis, fibrosis, and cirrhosis. The recent increase in the prevalence of the metabolic syndrome is largely driven by changes in diet and activity levels. Individual variation in the response to this obesogenic environment, however, is attributable in part to genetic variation between individuals, but very few mammalian genetic loci have been identified with effects on fat accumulation in the liver. To study the genetic basis for variation in liver fat content in response to dietary fat, liver fat proportion was determined using quantitative magnetic resonance imaging in 478 mice from 16 LG/J X SM/J recombinant inbred strains fed either a high-fat (42% kcal from fat) or low-fat (15% kcal from fat) diet. An analysis of variance confirmed that there is a genetic basis for variation in liver fat content within the population with significant effects of sex and diet. Three quantitative trail loci that contribute to liver fat content also were mapped. PMID:22973538

  8. Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism.

    PubMed

    Abruzzese, Giselle Adriana; Heber, Maria Florencia; Ferreira, Silvana Rocio; Velez, Leandro Martin; Reynoso, Roxana; Pignataro, Omar Pedro; Motta, Alicia Beatriz

    2016-07-01

    Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis. © 2016 Society for Endocrinology.

  9. Drospirenone/ethinyl estradiol.

    PubMed

    Rapkin, Andrea J; Sorger, Shelley N; Winer, Sharon A

    2008-02-01

    Drospirenone 3 mg/ethinyl estradiol 20 microg (24/4) is a new unique oral contraceptive formulation that combines in a novel dosing regimen the lowest dosage of ethinyl estradiol commonly used today with drospirenone, an innovative progestin. Drospirenone is a compound closely resembling progesterone, but with the antimineralocorticoid and antiandrogenic properties of a related therapeutic agent, the diuretic, antihypertensive and androgen receptor antagonist, 17alpha-spironolactone. The prolongation of hormonally active pills in the monthly drospirenone/ethinyl estradiol cycle from 21 days to 24 days, followed by 4 days of inactive pills, is an interesting variant of the recently developed extended pill regimens (1). Recent contraceptive research has focused on improving side effect profiles and providing noncontraceptive health and lifestyle advantages. Many of these benefits are now supported with evidence-based medicine (2). Most available oral contraceptives improve cycle regularity, menstrual pain, excessive menstrual flow and acne. However, weight gain, bloating, food cravings, breast tenderness and mood alterations (especially irritability and depression and the complex of affective, behavioral and somatic symptoms of premenstrual syndrome [PMS] and the severe form of PMS, premenstrual dysphoric disorder [PMDD]) are not generally improved with the traditional oral contraceptive formulations (3). Drospirenone/ethinyl estradiol 24/4 is currently the only hormonally based contraceptive regimen with large, randomized, controlled trials demonstrating efficacy for PMDD. It has received U.S. Food and Drug Administration (FDA) indications not only for the prevention of pregnancy but also for PMDD and for moderate acne vulgaris in women who choose oral contraception for birth control (4, 5). Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

  10. 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 ...

  11. 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 ...

  12. Short-term treatment of adult male zebrafish (Danio Rerio) with 17α-ethinyl estradiol affects the transcription of genes involved in development and male sex differentiation.

    PubMed

    Reyhanian Caspillo, Nasim; Volkova, Kristina; Hallgren, Stefan; Olsson, Per-Erik; Porsch-Hällström, Inger

    2014-08-01

    The synthetic estrogen 17α-ethinyl estradiol (EE2) disturbs reproduction and causes gonadal malformation in fish. Effects on the transcription of genes involved in gonad development and function that could serve as sensitive biomarkers of reproductive effects in the field is, however, not well known. We have studied mRNA expression in testes and liver of adult zebrafish (Danio rerio) males treated with 0, 5 or 25 ng/L EE2for 14 days. qPCR analysis showed that the mRNA expression of four genes linked to zebrafish male sex determination and differentiation, Anti-Mullerian Hormone, Double sex and mab-related protein, Sry-related HMG box-9a and Nuclear receptor subfamily 5 group number 1b were significantly decreased by 25 ng/L, but not 5 ng/L EE2 compared with the levels in untreated fish. The decreased transcription was correlated with a previously shown spawning failure in these males (Reyhanian et al., 2011. Aquat Toxicol 105, 41-48), suggesting that decreased mRNA expression of genes regulating male sexual function could be involved in the functional sterility. The mRNA level of Cytochrome P-45019a, involved in female reproductive development, was unaffected by hormone treatment. The transcription of the female-specific Vitellogenin was significantly induced in testes. While testicular Androgen Receptor and the Estrogen Receptor-alpha mRNA levels were unchanged, Estrogen receptor-beta was significantly decreased by 25 ng/L EE2. Hepatic Estrogen Receptor-alpha mRNA was significantly increased by both exposure concentrations, while Estrogen Receptor-beta transcription was unaltered. The decreased transcription of male-predominant genes supports a demasculinization of testes by EE2 and might reflect reproductive disturbances in the environment.

  13. 9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Livers affected with carotenosis; livers designated as âtelangiectatic,â âsawdust,â or âspotted.â 311.31 Section 311.31 Animals and Animal... DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.31 Livers affected with carotenosis;...

  14. 9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Livers affected with carotenosis; livers designated as âtelangiectatic,â âsawdust,â or âspotted.â 311.31 Section 311.31 Animals and Animal... DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.31 Livers affected with carotenosis;...

  15. 9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Livers affected with carotenosis; livers designated as âtelangiectatic,â âsawdust,â or âspotted.â 311.31 Section 311.31 Animals and Animal... DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.31 Livers affected with carotenosis;...

  16. 9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Livers affected with carotenosis; livers designated as âtelangiectatic,â âsawdust,â or âspotted.â 311.31 Section 311.31 Animals and Animal... DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.31 Livers affected with carotenosis;...

  17. 9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Livers affected with carotenosis; livers designated as âtelangiectatic,â âsawdust,â or âspotted.â 311.31 Section 311.31 Animals and Animal... DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.31 Livers affected with carotenosis;...

  18. Obesity affects the liver - the link between adipocytes and hepatocytes.

    PubMed

    Wree, Alexander; Kahraman, Alisan; Gerken, Guido; Canbay, Ali

    2011-01-01

    The incidence of obesity has dramatically increased in recent years. Consequently, obesity and associated disorders such as nonalcoholic fatty liver disease (NAFLD) constitute a serious threat. Therefore, the contribution of visceral adipose tissue to metabolic homeostasis has become a focus of interest. Visceral adipose tissue secretes free fatty acids (FFAs) and hormones, known as adipokines, and thus seems to play a major role in the development of NAFLD. Apoptotic cell death is a prominent feature in nonalcoholic steatohepatitis (NASH). Indeed, toxic FFAs can activate the intrinsic apoptosis pathway in hepatocytes via c-Jun N-terminal kinase (JNK). JNK activates the proapoptotic protein Bim, resulting in Bax activation and enhanced apoptosis, termed 'lipoapoptosis'. Reduced adiponectin levels may establish a proinflammatory milieu, thus increasing vulnerability to lipotoxicity, which promotes progression from simple steatosis to NASH and even advanced hepatic fibrosis. Moreover, obesity seems to be a risk factor for hepatocellular carcinoma, the most frequent liver cancer subtype. Even in acute liver failure, a high body mass index is associated with poor outcome, and recent data suggest a major role of obesity in the progression of chronic hepatitis C and B. This review summarizes current knowledge - highlighting the inflammatory and cytokine view - of the intimate relationship between adipose and liver tissue. Copyright © 2010 S. Karger AG, Basel.

  19. Estradiol Transdermal Patch

    MedlinePlus

    Most brands of estradiol transdermal patches are used to treat hot flushes (hot flashes; sudden strong feelings of heat ... different medication that does not contain estrogen. Most brands of estradiol transdermal patches are also sometimes used ...

  20. Effects of octylphenol and 17beta-estradiol on the gonads of guppies (Poecilia reticulata) exposed as adults via the water or as embryos via the mother.

    PubMed

    Kinnberg, Karin; Korsgaard, Bodil; Bjerregaard, Poul

    2003-01-01

    Endocrine disrupting alkylphenolic compounds have been found in the aquatic environment, and concern has arisen over the ability of these compounds to affect the reproductive system of fish. In this study, the effects of exposure to an environmentally relevant concentration of octylphenol or 17beta-estradiol on the gonad structure of fish were examined. Viviparous guppies (Poecilia reticulata) were exposed as adults via the water or as embryos via the mother to 26 microg/l octylphenol or 0.85 microg/l 17beta-estradiol (mean measured water concentrations). Histological examinations revealed effects of the exposures on the gonads of the fish exposed as adults. Indications of blocked spermatogonial mitosis were seen in the testis structure of adult males after exposure to octylphenol or 17beta-estradiol. The post-parturition ovaries of adult females exposed to 17beta-estradiol showed effects suggesting an inhibited yolk deposition. At the tested concentrations, exposure to octylphenol or 17beta-estradiol via the mother fish did not significantly affect the weight, length, gonopodium index or sex distribution of the offspring. However, histology revealed effects on the liver structure, suggesting some effect of maternal exposure to octylphenol or 17beta-estradiol. These findings indicate that although octylphenol and 17beta-estradiol affect the gonad structure of adult male and female guppies, these substances have no significant effects on the sexual differentiation of the embryos at the tested concentrations.

  1. Socioeconomic status does not affect the outcome of liver transplantation.

    PubMed

    Yoo, Hwan Y; Galabova, Violetta; Edwin, David; Thuluvath, Paul J

    2002-12-01

    The outcome of liver transplantation is dependent on many factors. It was suggested that racial disparities in outcome may be related to differences in socioeconomic status (SES). In this retrospective study, we analyzed the effect of SES on graft and patient survival. Two hundred seventy-six adult patients who underwent liver transplantation at our institution from July 1988 to June 2001 were included in the analysis. Educational and occupation statuses were coded using established criteria (Hollingshead Index of Social Status [HI]). SES then was calculated using the HI formula: SES = education level x 3 + occupation x 5, and categorized into four groups: group 1, score less than 29 (n = 71); group 2, score of 29 to 42 (n = 82); group 3, score of 42 to 53 (n = 69); and group 4, score greater than 53 (n = 54). Kaplan-Meier analysis was used for graft and patient survival, and Cox regression analysis was used to determine the effect of confounding factors. Demographics of all four groups were similar. One-, 2-, and 5-year graft and patient survival did not differ significantly across groups by Kaplan-Meier and Cox regression survival analysis. In conclusion, SES did not predict graft and patient survival after liver transplantation.

  2. Larval exposure to 4-nonylphenol and 17β-estradiol affects physiological and behavioral development of seawater adaptation in Atlantic salmon smolts

    USGS Publications Warehouse

    Lerner, Darrren T.; Bjornsson, Bjorn Thrandur; McCormick, Stephen D.

    2007-01-01

    Population declines of anadromous salmonids are attributed to anthropogenic disturbances including dams, commercial and recreational fisheries, and pollutants, such as estrogenic compounds. Nonylphenol (NP), a xenoestrogen, is widespread in the aquatic environment due to its use in agricultural, industrial, and household products. We exposed Atlantic salmon yolk-sac larvae to waterborne 10 or 100 μg L-1 NP (NP-L or NP-H, respectively), 2 μg L-1 17β-estradiol (E2), or vehicle, for 21 days to investigate their effects on smolt physiology and behavior 1 year later. NP-H caused approximately 50% mortality during exposure, 30 days after exposure, and 60 days after exposure. Mortality rates of NP-L and E2 fish were not affected until 60 days after treatment, when they were 4-fold greater than those of controls. Treatment with NP-L or E2 as yolk-sac larvae decreased gill sodium-potassium-activated adenosine triphosphatase (Na+,K+-ATPase) activity and seawater (SW) tolerance during smolt development, 1 year after exposure. Exposure to NP-L and E2 resulted in a latency to enter SW and reduced preference for SW approximately 2- and 5-fold, respectively. NP-L-exposed fish had 20% lower plasma insulin-like growth factor I (IGF-I) levels and 35% lower plasma triiodothyronine (T3). Plasma growth hormone and thyroxine (T4) were unaffected. Exposure to E2 did not affect plasma levels of IGF-I, GH, T3, or T4. Both treatment groups exhibited increased plasma cortisol and decreased osmoregulatory capacity in response to a handling stressor. These results suggest that early exposure to environmentally relevant concentrations of NP, and other estrogenic compounds, can cause direct and delayed mortalities and that this exposure can have long term, “organizational” effects on life-history events in salmonids.

  3. Comparison of ceftiofur hydrochloride and estradiol cypionate for metritis prevention and reproductive performance in dairy cows affected with retained fetal membranes.

    PubMed

    Risco, C A; Hernandez, J

    2003-06-01

    The objective of this study was to compare the effect of ceftiofur hydrochloride and estradiol cypionate (ECP) administration for metritis prevention and reproductive performance in dairy cows affected with retained fetal membranes (RFMs). After parturition, 97 dairy cows affected with RFM from a single dairy herd were randomly allocated to 1 of 3 treatment groups. Cows in-group 1 (n=31) were treated daily for 5 days with ceftiofur hydrochloride (2.2mg/kg, i.m.); cows in group 2 (n=33) were treated once with ECP (4 mg, i.m.); and cows in group 3 (n=33) were not treated. The proportion of cows with metritis, uterine involution patterns and the calving-to-conception interval were compared between groups. The proportion of cows that developed metritis was significantly different (P<0.05) in cows treated with ceftiofur hydrochloride (13%), compared with cows treated with ECP (42%) or cows that received no treatment (42%). Uterine involution patterns (i.e. median time to complete retraction of the uterus and mean diameter measure of cervix and uterine horns) were not significantly different between groups. Cows treated with ECP were 0.40 times as likely to conceive as control cows (P=0.05); median time to conception in cows treated with ECP (192 days) was longer, compared to control cows (124 days). We conclude that systemic administration of ceftioufur hydrochloride is beneficial for prevention of metritis, but its effect on reproductive performance was not significantly different to that of ECP or no treatment. In addition, administration of ECP did not have beneficial effects on metritis prevention and reproductive performance.

  4. Low dose exposure of diethylnitrosamine affects mice liver thymidine kinase.

    PubMed

    Pariat, T; Sharan, R N

    1995-11-17

    Swiss albino mice exposed to 5 and 10 mg diethylnitrosamine kg-1 body weight by intravenous route up to four weeks showed cyto- and genotoxic effects. Distortion of cell and nucleus shapes and extensive necrosis were observed. Thymidine kinase activity in the liver declined in diethylnitrosamine dose and duration dependent manners. The adult-form of thymidine kinase isozyme declined continuously during this period. Simultaneously, two isozymic forms of thymidine kinase, with small anodic migrations in an electrophoretic field, were gradually induced. Significance of theses changes in diethylnitrosamine induced precarcinogenic toxicity has been discussed.

  5. Diagnosis of uterine and vaginal disorders by different methodologies is affected by concentration of estradiol in plasma from lactating Holstein cows.

    PubMed

    Silper, B F; Madureira, A M L; Burnett, T A; Fernandes, A C C; Abreu, F M; Veira, D M; Vasconcelos, J L M; Cerri, R L A

    2016-06-01

    The relationship between plasma estradiol concentration at time of examination and prevalence of uterine disorders, agreement among methods, and associations of diagnosis with pregnancy hazard and milk yield was studied in 268 Holstein cows examined at 30±3 (exam 1) and 44±3 d in milk (DIM; exam 2). Purulent vaginal discharge was sampled using 2 methods: gloved hand and Metricheck (Simcro, Hamilton, New Zealand; PVD; score ≥3). Percentage of polymorphonuclear leukocytes was determined by endometrial cytology (CYTO; exam 1: ≥18%, exam 2: ≥10%); diameter of uterine horns (UTH; >20 mm), diameter of the inner layer of the cervix (CVX; >20.5 mm), presence of fluid in the uterine lumen (FL), and ovarian structures were evaluated by ultrasonography. A blood sample was collected at each exam for estradiol analysis. Prevalence at exams 1 and 2 was, respectively, 14.2 and 18.5% (PVD), 21.4 and 10.1% (FL), and 40.6 and 50.2% (CYTO). Prevalence of PVD at exam 1 was greater among cows with estradiol ≥2 pg/mL (19.4 vs. 8.2%). Agreement of all methods with CYTO was poor, the greatest being between CYTO and FL (exam 1; kappa=0.19). Agreement between CYTO and PVD, and between CYTO and FL (exam 1; kappa=0.15 and 0.35, respectively) was higher among cows with estradiol ≥2 pg/mL. Likelihood of PVD at exam 1 was greater if cows were positive for CVX [odds ratio (OR)=3.0], FL (OR=2.6) or had estradiol ≥2 pg/mL (OR=2.7). Likelihood of CYTO increased with dystocia (OR=2.3) and FL (OR=2.5). Estradiol did not influence diagnosis at exam 2. Positive FL or CYTO at exam 1 was associated with reductions in milk yield of 59 to 180 kg by 45 DIM. Pregnancy hazard until 250 DIM was reduced by CYTO at exam 1 (hazard ratio=0.74) and by PVD (hazard ratio=0.68) at exam 2. However, FL and CYTO reduced pregnancy hazard only when estradiol was ≥2 pg/mL (exam 1), whereas PVD reduced pregnancy hazard when diagnosed at exam 2 with estradiol <2 pg/mL. Overall, agreement was poor and effects of

  6. Factors affecting liver fat accumulation and liver hemorrhages associated with fatty liver-hemorrhagic syndrome in laying chickens.

    PubMed

    Lee, K; Flegal, C J; Wolford, J H

    1975-03-01

    A series of four experiments was conducted with a commercial strain of laying chickens in an attempt to experimentally produce Fatty Liver-Hemorrhagic syndrome (FLHS). Different dietary energy sources, environmental temperatures and feeding schedules were the experimental variables. Increasing the environmental temperature from 12.2 degrees C. (experiment 1) to 27.8 degrees C. (experiment 2) did not drastically alter total liver fat, 2.7 g. (experiment 1) vs. 2.9 g. (experiment 2) or the incidence of FLHS, 0.0% (experiment 1) vs. 1.0% (experiment 2). Likewise, in experiment 4, changing the environmental temperature from 22.2 degrees C. to 30.6 degrees C. or from 30.6 degrees C. to 22.2 degrees C. did not significantly (P greater than .05) alter total liver fat or liver wet weight. The greatest incidence (50%) of FLHS occurred in birds which were restricted in feed intake and exposed to an environmental temperature of 30.6 degrees C. from 32-36 weeks of age followed by ad libitum feeding at a temperature of 22.2 degrees C. from 36-40 weeks of age. These birds ate 26.8% more feed than the control birds during the ad libitum feeding period. Restricted feed schedules (experiment 3) resulted in significantly (P less than .05) lower 40 week liver wet weights and total fat when applied during the growing (14-20 weeks of age) and early lay (20-28 weeks of age) periods.

  7. 182 MATURATION OF BOVINE CUMULUS-OOCYTE COMPLEXES WITH FOLLICLE FLUID VARYING IN ESTRADIOL CONTENT AFFECTS CUMULUS CELL EXPANSION WITHOUT AFFECTING SUBSEQUENT EMBRYO DEVELOPMENT IN VITRO.

    PubMed

    Harl, A W; Larimore, E L; Al Naib, A; Wooldridge, L K; Ealy, A D; Perry, G A; Rhoads, M L

    2016-01-01

    The objective of this work was to determine how characteristics of bovine follicle fluid (FF; especially oestradiol content) affect cumulus cell expansion and oocyte competence. In the first study, FF was collected from abattoir-derived ovaries and pooled separately for large follicles (≥10mm) and small follicles (≤3mm). A portion of the FF from each category was charcoal stripped. These 4 types of FF were then used as the primary ingredient (75% vol/vol) in oocyte maturation media. A separate control group lacking FF but containing BSA was included to monitor potential impacts of protein on outcomes (control; without FF). Some of the cumulus-oocyte complexes (COC; n=250) were matured in individual drops for analysis of cumulus expansion (photographed and measured at 0 and 21h of maturation). Other COC (n=770) were matured in groups of 12 to 25 in the previously described media, and then subjected to IVF procedures. Cleavage rates were recorded on Day 3, and blastocyst rates were recorded on Day 8 post-fertilization. Cumulus cell expansion was greatest when COC were matured in medium containing FF from large follicles, wherein it even exceeded the controls (P<0.02). Maturation in FF from small follicles resulted in cumulus expansion that was intermediate between large and control. Maturation in charcoal-stripped FF severely restricted cumulus cell expansion (P<0.05) compared with those matured in untreated FF. Despite the observed improvement in cumulus cell expansion, COC that had been matured in media containing FF were less likely to cleave (P<0.05) and also less likely to develop to the blastocyst stage (P<0.01) than those matured in control medium. Cleavage and blastocyst rates did not differ among any of the maturation media containing FF. In the second study, oestrous cycles of 9 crossbred cows were synchronized and FF samples were collected 36 to 42h after prostaglandin F2α injection. Samples from individual cows were categorized as having high

  8. Estradiol release kinetics determine tissue response in ovariectomized rats.

    PubMed

    Otto, Christiane; Kantner, Ingrid; Nubbemeyer, Reinhard; Schkoldow, Jenny; Fuchs, Iris; Krahl, Elisabeth; Vonk, Richardus; Schüler, Christiane; Fritzemeier, Karl-Heinrich; Erben, Reinhold G

    2012-04-01

    Estrogen replacement is an effective therapy of postmenopausal symptoms such as hot flushes, bone loss, and vaginal dryness. Undesired estrogen effects are the stimulation of uterine and mammary gland epithelial cell proliferation as well as hepatic estrogenicity. In this study, we examined the influence of different estradiol release kinetics on tissue responsivity in ovariectomized (OVX) rats. Pulsed release kinetics was achieved by ip or sc administration of estradiol dissolved in physiological saline containing 10% ethanol (EtOH/NaCl) whereas continuous release kinetics was achieved by sc injection of estradiol dissolved in benzylbenzoate/ricinus oil (1+4, vol/vol). Initial 3-d experiments in OVX rats showed that pulsed ip estradiol administration had profoundly reduced stimulatory effects on the uterus and the liver compared with continuous release kinetics. On the other hand, both administration forms prevented severe vaginal atrophy. Based on these results, we compared the effects of pulsed (sc in EtOH/NaCl) vs. continuous (sc in benzylbenzoate/ricinus oil) estradiol release kinetics on bone, uterus, mammary gland, and liver in a 4-month study in OVX rats. Ovariectomy-induced bone loss was prevented by both administration regimes. However, pulsed estradiol resulted in lower uterine weight, reduced induction of hepatic gene expression, and reduced mammary epithelial hyperplasia relative to continuous estradiol exposure. We conclude that organ responsivity is influenced by different hormone release kinetics, a fact that might be exploited to reduce undesired estradiol effects in postmenopausal women.

  9. Changes in liver cell DNA methylation status in diabetic mice affect its FT-IR characteristics.

    PubMed

    Vidal, Benedicto de Campos; Ghiraldini, Flávia Gerelli; Mello, Maria Luiza S

    2014-01-01

    Lower levels of cytosine methylation have been found in the liver cell DNA from non-obese diabetic (NOD) mice under hyperglycemic conditions. Because the Fourier transform-infrared (FT-IR) profiles of dry DNA samples are differently affected by DNA base composition, single-stranded form and histone binding, it is expected that the methylation status in the DNA could also affect its FT-IR profile. The DNA FT-IR signatures obtained from the liver cell nuclei of hyperglycemic and normoglycemic NOD mice of the same age were compared. Dried DNA samples were examined in an IR microspectroscope equipped with an all-reflecting objective (ARO) and adequate software. Changes in DNA cytosine methylation levels induced by hyperglycemia in mouse liver cells produced changes in the respective DNA FT-IR profiles, revealing modifications to the vibrational intensities and frequencies of several chemical markers, including νas -CH3 stretching vibrations in the 5-methylcytosine methyl group. A smaller band area reflecting lower energy absorbed in the DNA was found in the hyperglycemic mice and assumed to be related to the lower levels of -CH3 groups. Other spectral differences were found at 1700-1500 cm(-1) and in the fingerprint region, and a slight change in the DNA conformation at the lower DNA methylation levels was suggested for the hyperglycemic mice. The changes that affect cytosine methylation levels certainly affect the DNA-protein interactions and, consequently, gene expression in liver cells from the hyperglycemic NOD mice.

  10. Identification of Plants That Inhibit Lipid Droplet Formation in Liver Cells: Rubus suavissimus Leaf Extract Protects Mice from High-Fat Diet-Induced Fatty Liver by Directly Affecting Liver Cells

    PubMed Central

    Takahashi, Tomohiro; Sugawara, Wataru; Takiguchi, Yuya; Takizawa, Kento; Nakabayashi, Ami; Nakamura, Mitsuo; Nagano-Ito, Michiyo; Ichikawa, Shinichi

    2016-01-01

    Fatty liver disease is a condition in which abnormally large numbers of lipid droplets accumulate in liver cells. Fatty liver disease induces inflammation under conditions of oxidative stress and may result in cancer. To identify plants that protect against fatty liver disease, we examined the inhibitory effects of plant extracts on lipid droplet formation in mouse hepatoma cells. A screen of 98 water extracts of plants revealed 4 extracts with inhibitory effects. One of these extracts, Rubus suavissimus S. Lee (Tien-cha or Chinese sweet tea) leaf extract, which showed strong inhibitory effects, was tested in a mouse fatty liver model. In these mouse experiments, intake of the plant extract significantly protected mice against fatty liver disease without affecting body weight gain. Our results suggest that RSE directly affects liver cells and protects them from fatty liver disease. PMID:27429636

  11. PNPLA3 I148M variant affects non-alcoholic fatty liver disease in liver transplant recipients.

    PubMed

    Liu, Zheng-Tao; Chen, Tian-Chi; Lu, Xiao-Xiao; Cheng, Jun; Xie, Hai-Yang; Zhou, Lin; Zheng, Shu-Sen

    2015-09-14

    De novo non-alcoholic fatty liver disease (NAFLD) is a common late complication for long-term survivors after liver transplantation. Genomic studies confirmed that PNPLA3 I148M and TM6SF2 E167K polymorphisms affected NAFLD susceptibility in the general population. However, this association was not validated in survivors after liver transplantation (LT). We performed a cross-sectional survey to investigate this relationship. A comprehensive survey, including anthropometric measurements, fasting venous blood sampling, ultrasound, and questionnaires was performed in the short-term. The clinical indications and patient's steatosis status before LT were collected from inpatient medical records. Sixty-five long-term recipients with a survival exceeding 10 years were enrolled in the final analysis. De novo NAFLD was more frequent in PNPLA3 GG carriers (0.33 vs 0.10 for GG vs CC + CG carriers, P = 0.018), while the genetic impact on NAFLD susceptibility was insignificant when categorized by the TM6SF2 polymorphism (0.19 in CC vs 0.14 in CT + TT carriers, P = 0.883). Multi-covariate analysis revealed that PNPLA3 exerted a significant genetic effect on de novo NAFLD following a recessive model (GG vs CC + CG, OR = 14.2, 95%CI: 1.78-113, P = 0.012). Compared to recipients with only the PNPLA3 GG allele or obesity (defined as body mass index > 25 kg/m(2)), steatosis was highly prevalent (71.4%) in PNPLA3 GG carriers with obesity. In conclusion, PNPLA3 I148M, but not TM6SF2 E167K, affects de novo NAFLD occurrence with a prominent interaction with obesity. Weight control might be a meaningful method to reduce the genetic susceptibility to NAFLD exerted by PNPLA3 variants.

  12. The effects of 6-Gingerol on reproductive improvement, liver functioning and Cyclooxygenase-2 gene expression in estradiol valerate - Induced polycystic ovary syndrome in Wistar rats.

    PubMed

    Pournaderi, Parisa Sadat; Yaghmaei, Parichehreh; Khodaei, Hamidreza; Noormohammadi, Zahra; Hejazi, Seyed Hossein

    2017-03-04

    6-Gingerol is the major pungent ingredient of ginger with anti-inflammatory and antioxidant properties. In this study, we evaluate the effects of 6-gingerol on the biochemical parameters and ovarian histological improvements in estradiol valerate (EV) induced PCOS rats. Thirty six female Wistar rats were divided into 4 groups: control, received normal diet, PCOS control, received 4 mg/kg EV injection for 28 days and two experimental groups, received an EV injection for 28 days and followed by 6-gingerol (200 μg/kg and 400 μg/kg) for 14 days. The administration of EV led to increase body and ovarian weights, abnormality in serum sex steroid profile, decrease in antioxidant activity and increase in COX-2 gene expression. 6-gingerol treatments, particularly the 400 μg/kg dose, markedly attenuated these alterations. 6-gingerol showed beneficial effects in the EV induced PCOS rats via decreased expression of COX-2, restored biochemical parameters to normal and decreased of cysts in the ovaries.

  13. Capacity of bioregulators of stem and progenitor cells to strongly affect liver redox-dependent processes.

    PubMed

    Cherkashina, Daria V; Tkacheva, Elena N; Somov, Alexander Y; Semenchenko, Olga A; Nardid, Oleg A; Petrenko, Alexander Y

    2011-12-01

    Abstract Effects of stem and progenitor cells or their compounds on recipient cells are investigated intensively today. In spite of this, their ability to interact with native cells and the final targets affected by them, particularly biochemical parameters that characterize cell redox-dependent processes, remain little studied. We have studied how bioregulators of stem and progenitor cells affect these processes in freshly isolated liver after animal pretreatment in vivo. Cytosol of human fetal mesenchymal-mesodermal tissues (8-10 weeks gestation) was administered intravenously; the control group was treated with Hanks' solution. After 4 hr, rats were sacrificed and their livers were isolated. To evaluate liver redox-dependent state, mitochondrial respiratory activity and nitroxyl radical and Alamar Blue™ reduction rates, mitochondrial and cytosolic glycerol kinase and nicotinamide adenine dinucleotide (NADH)-dependent malate dehydrogenase activities were studied. The results obtained demonstrate that bioregulators strongly affect liver redox-dependent processes, increasing mitochondrial respiration in state III and spin probe reduction rate and enhancing Alamar Blue™ reduction by glycolytic and nonglycolytic postmitochondrial enzymes. In addition, mitochondrial glycerol kinase and both isoforms of NADH-dependent malate dehydrogenase were inhibited. These data bring us closer to understanding stem and progenitor cell effects via directed regulation of metabolic redox-dependent processes.

  14. [Affective syndromes in liver transplant recipients: ¿mediated neurotoxicity immunosuppressive?].

    PubMed

    Restrepo, Diana Patricia; Tamayo, Alejandra

    2015-01-01

    The onset of affective and psychotic in liver transplant patients symptoms, raises the need to explore the possible etiologies of mental symptoms. Case report and literature review. Four clinical cases of patients undergoing orthotopic liver transplantation, who in the early post transplant showed affective symptoms, delusions and psychomotor agitation for which they needed psychiatric hospitalization and treatment with psychotropic drugs are presented. Three of the patients had clinical improvement and one patient died by suicide. The development of mental symptoms in the post-transplant period opens the possibility of considering the secondary organic mental disorder a basic condition. The adverse drug reaction may explain affective mental disorders in these four cases were reported. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  15. Blood Test: Estradiol

    MedlinePlus

    ... work so closely with one another, doctors often perform the estradiol test with tests for LH, FSH, testosterone (the male sex hormone — but teen and adult females produce some, too), and progesterone ( ...

  16. Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats

    PubMed Central

    Black, Katelyn L.; Daniel, Jill M.

    2016-01-01

    Abstract Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity. PMID:28032117

  17. Human liver estrone (E1), Estradiol (E2) and dehydroepiandrosterone (DHEA) sulfotransferases (STs): Comparison with thermostable (TS) and thermolabile (TL) phenol sulfotransferase (PST) activities

    SciTech Connect

    Hernandez, J.S.; Watson, R.W.G.; Weinshilboum, R.M. )

    1991-03-11

    Sulfation plays an important role in the metabolism of E1, E2 and DHEA in humans. The relationship between the enzymes that catalyze the sulfation of E1, E2 and DHEA and TS and TL PST is unclear. The authors compared thermal stability, sensitivity to inhibition by 2,6-dichloro-4-nitrophenol (DCNP) and individual variation in the regulation of these steroid ST activities with those of TS PST and TL PST in the human liver. E2 ST and TS PST had very similar thermal stabilities. The thermal inactivation profile of E1 ST suggested that this activity might be related to both DHEA ST and TS PST. DCNP inhibition studies also showed similar profiles for E2 ST and TS PST, with a small resistant component for E2 ST. A multiphasic profile for DCNP inhibition of E1 ST activity was found. Finally, studies performed with human liver sample showed significant correlations between E2 ST and TS PST, E1 ST and DHEA ST, E2 St and E1 ST, and, to a lesser degree, between E1 ST and TS PST and E2 ST and DHEA ST. TL PST was not correlated significantly with any of the other activities. These results suggest that the sulfation of E2 in human liver is catalyzed predominantly by TS PST, although DHEA ST may also play a role. Their results also suggest that the sulfation of E1 is catalyzed by DHEA ST and by TS PST, although other ST(s) could also be involved.

  18. Changes in Liver Cell DNA Methylation Status in Diabetic Mice Affect Its FT-IR Characteristics

    PubMed Central

    Vidal, Benedicto de Campos; Ghiraldini, Flávia Gerelli; Mello, Maria Luiza S.

    2014-01-01

    Background Lower levels of cytosine methylation have been found in the liver cell DNA from non-obese diabetic (NOD) mice under hyperglycemic conditions. Because the Fourier transform-infrared (FT-IR) profiles of dry DNA samples are differently affected by DNA base composition, single-stranded form and histone binding, it is expected that the methylation status in the DNA could also affect its FT-IR profile. Methodology/Principal Findings The DNA FT-IR signatures obtained from the liver cell nuclei of hyperglycemic and normoglycemic NOD mice of the same age were compared. Dried DNA samples were examined in an IR microspectroscope equipped with an all-reflecting objective (ARO) and adequate software. Conclusions/Significance Changes in DNA cytosine methylation levels induced by hyperglycemia in mouse liver cells produced changes in the respective DNA FT-IR profiles, revealing modifications to the vibrational intensities and frequencies of several chemical markers, including νas –CH3 stretching vibrations in the 5-methylcytosine methyl group. A smaller band area reflecting lower energy absorbed in the DNA was found in the hyperglycemic mice and assumed to be related to the lower levels of –CH3 groups. Other spectral differences were found at 1700–1500 cm−1 and in the fingerprint region, and a slight change in the DNA conformation at the lower DNA methylation levels was suggested for the hyperglycemic mice. The changes that affect cytosine methylation levels certainly affect the DNA-protein interactions and, consequently, gene expression in liver cells from the hyperglycemic NOD mice. PMID:25019512

  19. Liver-allocation policies for patients affected by HCC in Europe.

    PubMed

    De Carlis, Luciano; Di Sandro, Stefano; Centonze, Leonardo; Lauterio, Andrea; Buscemi, Vincenzo; De Carlis, Riccardo; Ferla, Fabio; Sguinzi, Raffaella; Okolicsanyi, Stefano; Belli, Luca; Strazzabosco, Mario

    2016-12-01

    The main goal of organ allocation systems is to guarantee an equal access to the limited resource of liver grafts for every patients on the waiting list, balancing between the ethical principles of equity, utility, benefit, need, and fairness. The European heath care scenario is very complex, as it is essentially decentralized and each Nation and Regions inside the nation, operate on a significant degree of autonomy. Furthermore the epidemiology of liver diseases and HCC, which is different among European countries, clearly inpacts on indications and priorities. The aims of this review are to analyze liver allocation policies for hepatocellular carcinoma, among different European. The European area considered for this analysis included 5 macro-areas or countries, which have similar policies for liver sharing and allocation: Centro Nazionale Trapianti (CNT) in Italy; Eurotransplant (Germany, the Netherlands, Belgium, Luxembourg, Austria, Hungary, Slovenia, and Croatia); Organizacion Nacional de Transplantes (ONT) in Spain; Etablissement français des Greffes (EfG) in France; NHS Blood & Transplant (NHSBT) in the United Kingdom and Ireland; Scandiatransplant (Sweden, Norway, Finland, Denmark, and Iceland). Each identified area, as network for organ sharing in Europe, adopts an allocation system based either on a policy center oriented or on a policy patient oriented. Priorization of patients affected by HCC in the waiting list for deceased donors liver transplant worldwide is dominated by 2 main principles: urgency and utility. Despite the absence of a common organs allocation policy over the Eurpean countries, long-term survival patients listed for transplant due to HCC are comparable to the long-term survival reported in the UNOS register. However, as the principles of allocation are being re-discussed and new proposals emerge, and the epidemiology of liver disease changes, an effort toward a common system is highly advisable.

  20. Low 17beta-estradiol levels in CNR1 knock-out mice affect spermatid chromatin remodeling by interfering with chromatin reorganization.

    PubMed

    Cacciola, Giovanna; Chioccarelli, Teresa; Altucci, Lucia; Ledent, Catherine; Mason, J Ian; Fasano, Silvia; Pierantoni, Riccardo; Cobellis, Gilda

    2013-06-01

    The type 1-cannabinoid receptor, CNR1, regulates differentiation of spermatids. Indeed, we have recently reported that the genetic inactivation of Cnr1 in mice influenced chromatin remodeling of spermatids, by reducing histone displacement and then sperm chromatin quality indices (chromatin condensation and DNA integrity). Herein, we have studied, at both central and testicular levels, the molecular signals potentially involved in histone displacement. In particular, investigation of the neuroendocrine axis involved in estrogen production demonstrated down-regulation of the axis supporting FSH/estrogen secretion in Cnr1-knockout male mice. Conversely, Cnr1-knockout male mice treated with 17beta-estradiol showed a weak increase of pituitary Fsh-beta subunit mRNA levels and a rescue of sperm chromatin quality indices demonstrating that estrogens, possibly in combination with FSH secretion, play an important role in regulating chromatin remodeling of spermatids.

  1. Celecoxib affects estrogen sulfonation catalyzed by several human hepatic sulfotransferases, but does not stimulate 17-sulfonation in rat liver.

    PubMed

    Ambadapadi, Sriram; Wang, Peter L; Palii, Sergiu P; James, Margaret O

    2017-09-01

    Celecoxib is known to alter the preferred position of SULT2A1-catalyzed sulfonation of 17β-estradiol (17β-E2) and other estrogens from the 3- to the 17-position. Understanding the effects of celecoxib on estrogen sulfonation is of interest in the context of the investigational use of celecoxib to treat breast cancer. This study examined the effects on celecoxib on cytosolic sulfotransferases in human and rat liver and on SULT enzymes known to be expressed in liver. Celecoxib's effects on the sulfonation of several steroids catalyzed by human liver cytosol were similar but not identical to those observed previously for SULT2A1. Celecoxib was shown to inhibit recombinant SULT1A1-catalyzed sulfonation of 10nM estrone and 4μM p-nitrophenol with IC50 values of 2.6 and 2.1μM, respectively, but did not inhibit SULT1E1-catalyzed estrone sulfonation. In human liver cytosol, the combined effect of celecoxib and known SULT1A1 and 1E1 inhibitors, quercetin and triclosan, resulted in inhibition of 17β-E2-3-sulfonation such that the 17-sulfate became the major metabolite: this is of interest because the 17-sulfate is not readily hydrolyzed by steroid sulfatase to 17β-E2. Investigation of hepatic cytosolic steroid sulfonation in rat revealed that celecoxib did not stimulate 17β-E2 17-sulfonation in male or female rat liver as it does with human SULT2A1 and human liver cytosol, demonstrating that rat is not a useful model of this effect. In silico studies suggested that the presence of the bulky tryptophan residue in the substrate-binding site of the rat SULT2A homolog instead of glycine as in human SULT2A1 may explain this species difference. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The European Policy for Liver Allocation in Patients Affected by Hepatocellular Carcinoma.

    PubMed

    Sandro, Stefano Di; Ferla, Fabio; Lauterio, Andrea; Mangoni, Iacopo; Carlis, Riccardo De; Buscemi, Vincenzo; Carlis, Luciano De

    2017-01-01

    The main goal of allocation system is to guarantee an equal access to the limited resource of liver grafts for every class of patients on the waiting list, balancing between the ethical principles of equity, utility, benefit, need, and fairness. The aim of this review was to analyze liver allocation policies among these organizations, focusing on HCC. The European area considered for this analysis included 6 macro-areas or countries, which are congregated from the same policy of liver sharing and allocation. By this definition, the 6 areas identified are: Centro Nazionale Trapianti (CNT) in Italy; Eurotransplant (Germany, the Netherlands, Belgium, Luxembourg, Austria, Hungary, Slovenia, and Croatia); Organizacion Nacional de Transplantes (ONT) in Spain; Etablissement francais des Greffes (EfG) in France; NHS Blood Transplant (NHSBT) in the United Kingdom and Ireland; Scandiatransplant (Sweden, Norway, Finland, Denmark, and Iceland); Romanian National Policy. Each identified area, as network for organ sharing in Europe, adopts a basic allocation system that consider a policy center oriented or patient oriented. Priorization of patients affected by HCC in the waiting list for deceased donors liver transplant worldwide is dominated by 2 main principles: urgency and utility. The main message of this review is the absence of a common organs allocation policy over the Eurpean countries. Despite that, long-term survival of the community of patients listed for transplant due to HCC results, however, highly acceptable in Europe and comparable to the long-term survial reported in the UNOS register. Celsius.

  3. Wilson's disease: changes in methionine metabolism and inflammation affect global DNA methylation in early liver disease.

    PubMed

    Medici, Valentina; Shibata, Noreene M; Kharbanda, Kusum K; LaSalle, Janine M; Woods, Rima; Liu, Sarah; Engelberg, Jesse A; Devaraj, Sridevi; Török, Natalie J; Jiang, Joy X; Havel, Peter J; Lönnerdal, Bo; Kim, Kyoungmi; Halsted, Charles H

    2013-02-01

    Hepatic methionine metabolism may play an essential role in regulating methylation status and liver injury in Wilson's disease (WD) through the inhibition of S-adenosylhomocysteine hydrolase (SAHH) by copper (Cu) and the consequent accumulation of S-adenosylhomocysteine (SAH). We studied the transcript levels of selected genes related to liver injury, levels of SAHH, SAH, DNA methyltransferases genes (Dnmt1, Dnmt3a, Dnmt3b), and global DNA methylation in the tx-j mouse (tx-j), an animal model of WD. Findings were compared to those in control C3H mice, and in response to Cu chelation by penicillamine (PCA) and dietary supplementation of the methyl donor betaine to modulate inflammatory and methylation status. Transcript levels of selected genes related to endoplasmic reticulum stress, lipid synthesis, and fatty acid oxidation were down-regulated at baseline in tx-j mice, further down-regulated in response to PCA, and showed little to no response to betaine. Hepatic Sahh transcript and protein levels were reduced in tx-j mice with consequent increase of SAH levels. Hepatic Cu accumulation was associated with inflammation, as indicated by histopathology and elevated serum alanine aminotransferase (ALT) and liver tumor necrosis factor alpha (Tnf-α) levels. Dnmt3b was down-regulated in tx-j mice together with global DNA hypomethylation. PCA treatment of tx-j mice reduced Tnf-α and ALT levels, betaine treatment increased S-adenosylmethionine and up-regulated Dnmt3b levels, and both treatments restored global DNA methylation levels. Reduced hepatic Sahh expression was associated with increased liver SAH levels in the tx-j model of WD, with consequent global DNA hypomethylation. Increased global DNA methylation was achieved by reducing inflammation by Cu chelation or by providing methyl groups. We propose that increased SAH levels and inflammation affect widespread epigenetic regulation of gene expression in WD. Copyright © 2012 American Association for the Study of

  4. 17β-Estradiol protects against acetaminophen-overdose-induced acute oxidative hepatic damage and increases the survival rate in mice.

    PubMed

    Chandrasekaran, Victor Raj Mohan; Periasamy, Srinivasan; Liu, Li-Lian; Liu, Ming-Yie

    2011-01-01

    Acetaminophen overdose causes acute liver injury or even death in both humans and experimental animals. We investigated the effect of 17β-estradiol against acetaminophen-induced acute liver injury and mortality in mice. Male mice were given acetaminophen (p-acetamidophenol; 300 mg/kg; orally) to induce acute liver injury. Acetaminophen significantly increased the levels of aspartate transaminase, alanine transaminase, myeloperoxidase, lipid peroxidation, and glutathione reductase, but it decreased superoxide dismutase, catalase, and glutathione. In addition, acetaminophen-induced mortality began 4h post-treatment, and all mice died within 9h. 17β-Estradiol (200 μg/kg; i.p.) protected against acetaminophen-induced oxidative hepatic damage by inhibiting neutrophil infiltration and stimulating the antioxidant defense system. However, 17β-estradiol did not affect acetaminophen-induced glutathione depletion or increased glutathione reductase activity. We conclude that 17β-estradiol specifically attenuates acute hepatic damage and decreases mortality in acetaminophen-overdosed male mice.

  5. Choline treatment affects the liver reticuloendothelial system and plasma fatty acid composition in diabetic rats.

    PubMed

    Al-Saeedi, Fatma J; Cheng, Behling

    2013-07-01

    This study investigated effects of choline treatment on hepatic reticuloendothelial and biliary functions and plasma fatty acid composition in diabetic rats. Diabetes was induced by streptozotocin (STZ). Choline was administered to untreated rats and a portion of STZ-treated rats for two sequences of five consecutive days, separated by a 2-day interval. Hepatic functions were studied using (99m) Tc Tin (II) colloid (TIN) and 99 mTc mebrofenin [bromo-iminodiacetic acid (BrIDA)] imaging. The TIN-uptake ratios (organ/whole body) of heart, liver and spleen, and the BrIDA-uptake ratios (organ or tissue/whole body) of liver, biliary tree and abdomen were obtained following imaging studies. Fatty acids were analysed by GC/MS. Choline treatment did not attenuate hyperglycaemic development. Diabetic rats showed (i) a decreased TIN-uptake ratio in liver with co-increased ratios in heart and spleen; choline treatment diminished these changes, (ii) elevated BrIDA-uptake ratios in biliary tree and abdomen but not in liver; choline treatment did not attenuate the elevations and (iii) decreases in plasma palmitoleic acid and oleic acid, reflecting an impaired stearoyl-CoA desaturase function; choline treatment did not affect the diminutions, but caused a decrease in arachidonic acid with a co-increase in linoleic acid. Some rats developed hypoproteinemia (HPO). HPO rats also exhibited decreases in plasma palmitoleic acid and oleic acid. Diabetes caused almost absence of palmitoleic acid in HPO rats. Choline treatment exerted no effect on the plasma fatty acid composition of diabetic HPO rats. Choline treatment affected hepatic reticuloendothelial function and plasma fatty acid composition, but not hepatobiliary function, in diabetic rats. Whether choline treatment is beneficial requires further studies. © 2013 The Authors Clinical Physiology and Functional Imaging © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  6. Cognitive effects of estradiol after menopause

    PubMed Central

    St. John, Jan A.; Hodis, Howard N.; McCleary, Carol A.; Stanczyk, Frank Z.; Shoupe, Donna; Kono, Naoko; Dustin, Laurie; Allayee, Hooman; Mack, Wendy J.

    2016-01-01

    Objective: To test the hypothesis that effects of estrogen-containing hormone therapy on cognitive abilities differ between postmenopausal women near to, and further from, menopause. Methods: In this randomized, double-blind, placebo-controlled trial, healthy women within 6 years of menopause or 10+ years after menopause were randomly assigned to oral 17β-estradiol 1 mg/d or placebo. Women with a uterus received cyclic micronized progesterone vaginal gel or placebo. The primary outcome assessed at 2.5 and 5 years, compared between treatment groups, was change in a standardized composite of neuropsychological test scores assessing verbal episodic memory. Secondary outcomes assessed executive functions and global cognition. Results: A total of 567 women were included in modified intention-to-treat analyses after a mean treatment duration of 57 months. For verbal memory, the mean estradiol minus placebo standardized difference in composite scores (−0.06, 95% confidence interval −0.22 to 0.09) was not significant (2-tailed p = 0.33). Differences were similar in early and late postmenopause groups (2-tailed interaction p = 0.88). Interactions between postmenopause groups and differences between treatment groups were not significant for executive functions or global cognition. Conclusions: Estradiol initiated within 6 years of menopause does not affect verbal memory, executive functions, or global cognition differently than therapy begun 10+ years after menopause. Estradiol neither benefits nor harms these cognitive abilities regardless of time since menopause. Classification of evidence: This study provides Class I evidence that estradiol initiated within 6 years of menopause does not affect cognition at 2.5 years differently than estradiol initiated 10+ years after menopause. PMID:27421538

  7. The hyperventilation of cirrhosis: progesterone and estradiol effects.

    PubMed

    Lustik, S J; Chhibber, A K; Kolano, J W; Hilmi, I A; Henson, L C; Morris, M C; Bronsther, O

    1997-01-01

    Progesterone and estradiol are metabolized in the liver and are elevated in patients with cirrhosis. Progesterone stimulates ventilation by activating progesterone receptors in the central nervous system; estradiol may facilitate progesterone's actions by increasing progesterone receptors. This study evaluated whether progesterone and estradiol contribute to the respiratory alkalosis common in cirrhotic patients. Arterial blood gases and progesterone and estradiol levels were obtained in 50 patients with cirrhosis. Multiple linear regression revealed a statistically significant correlation between PaCO2 and progesterone and estradiol (r = .54, P < .05). Patients with severe hyperventilation (PaCO2 < or = 30 mm Hg) had statistically higher levels of progesterone and estradiol than did patients with mild hyperventilation (30 < PaCO2 < or = 35) or normal ventilation (PaCO2 > 35) (P < .05). Although the progesterone levels were two orders of magnitude lower than those associated with hyperventilation in pregnant patients, the increased ventilatory effect may be because of the altered blood-brain barrier (BBB) present in cirrhotic patients. Progesterone and estradiol appear to contribute to the hyperventilation in cirrhotic patients.

  8. Selenium affects the expression of GPx4 and catalase in the liver of chicken.

    PubMed

    Zoidis, E; Pappas, A C; Georgiou, C A; Komaitis, Epsilon; Feggeros, K

    2010-03-01

    A total of 128 chickens (Gallus gallus, broilers) were used to investigate the effect of organic selenium (Se) in expression of catalase (CAT) and phospholipid hydroperoxidase 4 (GPx4) genes. There were 4 replicates of 4 dietary treatments: T1 (basal diet with no added Se), T2 (T1 with 0.15 ppm Se added), T3 (T1 with 0.3 ppm Se) and T4 (T1 with 3.0 ppm Se). At 4th and 6th week, 2 chickens per replicate pen were sacrificed for whole blood and liver sample collections. Samples were analyzed for total Se by ICP-MS and gene expression by RT-PCR. Dietary supplementation with organic Se (Se-yeast) readily elevated its concentration in the tissues. GPx4 mRNA levels, pooled for both ages, of chickens fed T3 and T4 diets were significantly reduced compared to those fed diet T1 by 47% and 77% respectively, while that of T2 did not differ. Liver CAT mRNA levels at 4th week were significantly decreased as Se supplementation increased, while at 6th week, were not significantly affected by Se. The study showed that liver GPx4 mRNA levels could be down-regulated by excess of Se. It is possible that reserves built by excess of Se meet antioxidant requirements and no additional GPx4 transcription is necessary. 2009 Elsevier Inc. All rights reserved.

  9. Viral load affects the immune response to HBV in mice with humanized immune system and liver.

    PubMed

    Dusséaux, Mathilde; Masse-Ranson, Guillemette; Darche, Sylvie; Ahodantin, James; Li, Yan; Fiquet, Oriane; Beaumont, Elodie; Moreau, Pierrick; Rivière, Lise; Neuveut, Christine; Soussan, Patrick; Roingeard, Philippe; Kremsdorf, Dina; Di Santo, James P; Strick-Marchand, Helene

    2017-08-26

    Hepatitis B virus (HBV) infects hepatocytes, but the mechanisms of the immune response against the virus, and how it affects disease progression, are unclear. We performed studies with BALB/c Rag2(-/-)Il2rg(-/-)Sirpa(NOD)Alb-uPA(tg/tg) mice, stably engrafted with human hepatocytes (HUHEP) with or without a human immune system (HIS). HUHEP and HIS-HUHEP mice were given an intraperitoneal injection of HBV. Mononuclear cells were isolated from spleen and liver for analysis by flow cytometry. Liver was analyzed by immunohistochemistry and mRNA levels were measured by quantitative reverse transcription PCR. Plasma levels of HBV DNA was quantified by quantitative PCR, and antigen-specific antibodies were detected by immunocytochemistry of HBV transfected BHK-21 cells. Following HBV infection, a complete viral life cycle, with production of HBV DNA, hepatitis B e, core (HBc) and surface (HBs) antigens, and covalently closed circular DNA, was observed in HUHEP and HIS-HUHEP mice. HBV replicated unrestricted in HUHEP mice resulting in high viral titers without pathologic effects. In contrast, HBV-infected HIS-HUHEP mice developed chronic hepatitis with 10-fold lower titers and antigen-specific IgGs, (anti-HBs, anti-HBc), consistent with partial immune control. HBV-infected HIS-HUHEP livers contained infiltrating Kupffer cells, mature activated natural killer cells (CD69+), and PD-1+ effector memory T cells (CD45RO+). Reducing the viral inoculum resulted in more efficient immune control. Plasma from HBV-infected HIS-HUHEP mice had increased levels of inflammatory and immune-suppressive cytokines (C-X-C motif chemokine ligand 10 and interleukin 10), which correlated with populations of intrahepatic CD4+ T cells (CD45RO+PD-1+). Mice with high levels of viremia had HBV-infected liver progenitor cells. Giving the mice the nucleoside analogue entecavir reduced viral loads and decreased liver inflammation. In HIS-HUHEP mice, HBV infection completes a full life cycle and

  10. Wilson disease: changes in methionine metabolism and inflammation affect global DNA methylation in early liver disease

    PubMed Central

    Medici, Valentina; Shibata, Noreene M.; Kharbanda, Kusum K.; LaSalle, Janine M.; Woods, Rima; Liu, Sarah; Engelberg, Jesse A.; Devaraj, Sridevi; Török, Natalie J.; Jiang, Joy X.; Havel, Peter J.; Lönnerdal, Bo; Kim, Kyoungmi; Halsted, Charles H.

    2012-01-01

    Hepatic methionine metabolism may play an essential role in regulating methylation status and liver injury in Wilson disease (WD) through the inhibition of S-adenosylhomocysteine hydrolase (SAHH) by copper (Cu) and the consequent accumulation of S-adenosylhomocysteine (SAH). We studied the transcript levels of selected genes related to liver injury, levels of SAHH, SAH, DNA methyltransferases genes (Dnmt1, Dnmt3a, Dnmt3b) and global DNA methylation in the tx-j mouse (tx-j), an animal model of WD. Findings were compared to those in control C3H mice, and in response to Cu chelation by penicillamine (PCA) and dietary supplementation of the methyl donor betaine to modulate inflammatory and methylation status. Transcript levels of selected genes related to endoplasmic reticulum stress, lipid synthesis, and fatty acid oxidation were down-regulated at baseline in tx-j mice, further down-regulated in response to PCA, and showed little to no response to betaine. Hepatic Sahh transcript and protein levels were reduced in tx-j mice with consequent increase of SAH levels. Hepatic Cu accumulation was associated with inflammation, as indicated by histopathology and elevated serum ALT and liver tumor necrosis factor alpha (Tnf-α) levels. Dnmt3b was down-regulated in tx-j mice together with global DNA hypomethylation. PCA treatment of tx-j mice reduced Tnf-α and ALT levels, betaine treatment increased S-adenosylmethionine and up-regulated Dnmt3b levels, and both treatments restored global DNA methylation levels. Conclusion: reduced hepatic Sahh expression was associated with increased liver SAH levels in the tx-j model of WD, with consequent global DNA hypomethylation. Increased global DNA methylation was achieved by reducing inflammation by Cu chelation or by providing methyl groups. We propose that increased SAH levels and inflammation affect widespread epigenetic regulation of gene expression in WD. PMID:22945834

  11. The Post-Ovariectomy Interval Affects the Antidepressant-Like Action of Citalopram Combined with Ethynyl-Estradiol in the Forced Swim Test in Middle Aged Rats.

    PubMed

    Vega Rivera, Nelly M; Gallardo Tenorio, Alfredo; Fernández-Guasti, Alonso; Estrada Camarena, Erika

    2016-05-03

    The use of a combined therapy with low doses of estrogens plus antidepressants to treat depression associated to perimenopause could be advantageous. However the use of these combinations is controversial due to several factors, including the time of intervention in relation to menopause onset. This paper analyzes whether time post-OVX influences the antidepressant-like action of a combination of ethynyl-estradiol (EE₂) and citalopram (CIT) in the forced swim test (FST). Middle-aged (15 months old) female Wistar rats were ovariectomized and after one or three weeks treated with EE₂ (1.25, 2.5 or 5.0 µg/rat, s.c.; -48 h) or CIT (1.25, 2.5, 5.0 or 10 mg/kg, i.p./3 injections in 24 h) and tested in the FST. In a second experiment, after one or three weeks of OVX, rats received a combination of an ineffective dose of EE₂ (1.25 µg/rat, s.c., -48 h) plus CIT (2.5 mg/kg, i.p./3 injections in 24 h) and subjected to the FST. Finally, the uteri were removed and weighted to obtain an index of the peripheral effects of EE₂ administration. EE₂ (2.5 or 5.0 µg/rat) reduced immobility after one but not three weeks of OVX. In contrast, no CIT dose reduced immobility at one or three weeks after OVX. When EE₂ (1.25 µg/rat) was combined with CIT (2.5 mg/kg) an antidepressant-like effect was observed at one but not three weeks post-OVX. The weight of the uteri augmented when EE₂ was administrated three weeks after OVX. The data suggest that the time post-OVX is a crucial factor that contributes to observe the antidepressant-like effect of EE₂ alone or in combination with CIT.

  12. 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...

  13. 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...

  14. Factors affecting surgical margin recurrence after hepatectomy for colorectal liver metastases

    PubMed Central

    Akyuz, Muhammet; Aucejo, Federico; Quintini, Cristiano; Miller, Charles; Fung, John

    2016-01-01

    Background Hepatic recurrence after resection of colorectal liver metastasis (CLM) occurs in 50% of patients during follow-up, with 2.8% to 13.9% presenting with surgical margin recurrence (SMR). The aim of this study is to analyze factors that related to SMR in patients with CLM undergoing hepatectomy. Methods Demographics, clinical and survival data of patients who underwent hepatectomy were identified from a prospectively maintained, institutional review board (IRB)-approved database between 2000 and 2012. Statistical analysis was performed using univariate Kaplan Meier and Cox proportional hazard model. Results There were 85 female and 121 male patients who underwent liver resection for CLM. An R0 resection was performed in 157 (76%) patients and R1 resection in 49. SMR was detected in 32 patients (15.5%) followed up for a median of 29 months (range, 3–121 months). A half of these patients had undergone R1 (n=16) and another half R0 resection (n=16). Tumor size, preoperative carcinoembryonic antigen (CEA) level and margin status were associated with SMR on univariate analysis. On multivariate analysis, a positive surgical margin was the only independent predictor of SMR. The receipt of adjuvant chemotherapy did not affect margin recurrence. SMR was an independent risk factor associated with worse disease-free (DFS) and overall survival (OS). Conclusions This study shows that SMR, which can be detected in up to 15.5% of patients after liver resection for CLM, adversely affects DFS and OS. The fact that a positive surgical margin was the only predictive factor for SMR in these patients underscores the importance of achieving negative margins during hepatectomy. PMID:27294032

  15. Listening to the consumer voice: developing multilingual cancer information resources for people affected by liver cancer.

    PubMed

    Robotin, Monica C; Porwal, Mamta; Hopwood, Max; Nguyen, Debbie; Sze, Minglo; Treloar, Carla; George, Jacob

    2017-02-01

    In Australia, liver cancer incidence is rising, particularly among people born in hepatitis B-endemic countries. We sought to build an understanding of the information needs of people affected by liver cancer, to inform the design of in-language consumer information resources. We searched the World Wide Web for available in-language consumer information and conducted a literature search on consumers' information needs and their preferred means of accessing it. Qualitative data collection involved bilingual researchers conducting focus group discussions (26 participants) and in-depth interviews (22 participants) with people affected by liver cancer in English, Vietnamese, Cantonese and Mandarin. Sessions were audio-recorded, transcribed, translated and thematically analysed. The key themes and salient findings informed the development of in-language multimedia information resources. Many consumer resources did not cater for people with low literacy levels. The participants wanted more information on cancer diagnostic and treatment options, nutrition and Chinese Medicine and experienced communication challenges speaking to health professionals. While Vietnamese speakers relied entirely on information provided by their doctors, other participants actively searched for additional treatment information and commonly used the Internet to source it. We developed multilingual, multimedia consumer information resources addressing identified consumer information needs through an iterative process, in collaboration with our multilingual consumer panel. These resources are available in four languages, as separate modules accessible online and in DVD format. This process enabled the development of user-friendly patient resources, which complement health-care provider information and supports informed patient decision making. © 2016 The Authors. Health Expectations Published by John Wiley & Sons Ltd.

  16. Body Posture Angle Affects the Physiological Indices of Patients With Liver Cirrhosis Ascites.

    PubMed

    Hsu, Wen-chuan; Ho, Lun-hui; Lin, Mei-hsiang; Chiu, Hsiu-ling

    2016-01-01

    The study objective was to compare the effect of different angles of lying positions on the physiological indices of patients with cirrhosis ascites. Chronic liver disease and cirrhosis were ranked 9th among the top 10 causes of death. Ascites is the most common cirrhosis comorbidity. Body posture can affect pulmonary ventilation and arterial oxygen partial pressure, making it an important clinical nursing intervention significantly affecting patient recovery. This was a quasi-experimental study design. From a medical center in Taiwan, 252 patients with cirrhosis ascites were recruited. Subjects were randomly divided into three groups by bed angle: 15°, 30°, and 45°. Physiological indices were measured at 5, 10, 15, 20, 25, and 30 minutes to determine any changes in heart rate, respiration rate, and oxygenation saturation. Data analysis included descriptive statistics and the generalized estimating equation for statistical analysis with significance set at α= 0.05. After controlling for confounding variables, the three groups differed significantly in heart rate at 20, 25, and 30 minutes, oxygenation saturations at 15 and 20 minutes, and respiration rate at 5 and 10 minutes (α< 0.05). Body posture can affect pulmonary ventilation and arterial oxygen partial pressure and is thus an important clinical nursing intervention that significantly affects the recovery of patients. When caring for patients with cirrhosis ascites, nurses should help patients to choose the most comfortable angle for them with no particular restrictions. Our results can be used to guide nurses in making a plan for health education and nursing that improves the quality of care for patients with chronic liver disease and cirrhosis patients with ascites.

  17. The Post-Ovariectomy Interval Affects the Antidepressant-Like Action of Citalopram Combined with Ethynyl-Estradiol in the Forced Swim Test in Middle Aged Rats

    PubMed Central

    Vega Rivera, Nelly M.; Gallardo Tenorio, Alfredo; Fernández-Guasti, Alonso; Estrada Camarena, Erika

    2016-01-01

    The use of a combined therapy with low doses of estrogens plus antidepressants to treat depression associated to perimenopause could be advantageous. However the use of these combinations is controversial due to several factors, including the time of intervention in relation to menopause onset. This paper analyzes whether time post-OVX influences the antidepressant-like action of a combination of ethynyl-estradiol (EE2) and citalopram (CIT) in the forced swim test (FST). Middle-aged (15 months old) female Wistar rats were ovariectomized and after one or three weeks treated with EE2 (1.25, 2.5 or 5.0 µg/rat, s.c.; −48 h) or CIT (1.25, 2.5, 5.0 or 10 mg/kg, i.p./3 injections in 24 h) and tested in the FST. In a second experiment, after one or three weeks of OVX, rats received a combination of an ineffective dose of EE2 (1.25 µg/rat, s.c., −48 h) plus CIT (2.5 mg/kg, i.p./3 injections in 24 h) and subjected to the FST. Finally, the uteri were removed and weighted to obtain an index of the peripheral effects of EE2 administration. EE2 (2.5 or 5.0 µg/rat) reduced immobility after one but not three weeks of OVX. In contrast, no CIT dose reduced immobility at one or three weeks after OVX. When EE2 (1.25 µg/rat) was combined with CIT (2.5 mg/kg) an antidepressant-like effect was observed at one but not three weeks post-OVX. The weight of the uteri augmented when EE2 was administrated three weeks after OVX. The data suggest that the time post-OVX is a crucial factor that contributes to observe the antidepressant-like effect of EE2 alone or in combination with CIT. PMID:27153072

  18. Sample, testing and analysis variables affecting liver mechanical properties: A review.

    PubMed

    Mattei, Giorgio; Ahluwalia, Arti

    2016-11-01

    Given the critical role of liver mechanics in regulating cell response and directing the development of tissue fibrosis, accurately characterising its mechanical behaviour is of relevance for both diagnostic purposes as well as for tissue engineering and for the development of in-vitro models. Determining and quantifying the mechanical behaviour of soft biological tissues is, however, highly challenging due to their intrinsic labile nature. Indeed, a unique set of values of liver mechanical properties is still lacking to date; testing conditions can significantly affect sample status and hence the measured behaviour and reported results are strongly dependent on the adopted testing method and configuration as well as sample type and status. This review aims at summarising the bulk mechanical properties of liver described in the literature, discussing the possible sources of variation and their implications on the reported results. We distinguish between the intrinsic mechanical behaviour of hepatic tissue, which depends on sample variables, and the measured mechanical properties which also depend on the testing and analysis methods. Finally, the review provides guidelines on tissue preparation and testing conditions for generating reproducible data which can be meaningfully compared across laboratories. Soft tissue mechanics is widely investigated, but poorly understood. This review identifies and discusses sample and testing variables which can influence the mechanical behaviour of hepatic tissue and consequently the measured mechanical properties. To encourage the biomaterial community towards more standardized testing of soft tissues and enable comparisons between data from different laboratories, we have established new testing methods and experimental recommendations for sample preparation and testing. The review could be of wide interest to scientists involved in biomaterials research because it addresses and proposes guidelines for several issues related to

  19. Estradiol and the Developing Brain

    PubMed Central

    McCarthy, Margaret M.

    2009-01-01

    Estradiol is the most potent and ubiquitous member of a class of steroid hormones called estrogens. Fetuses and newborns are exposed to estradiol derived from their mother, their own gonads, and synthesized locally in their brains. Receptors for estradiol are nuclear transcription factors that regulate gene expression but also have actions at the membrane, including activation of signal transduction pathways. The developing brain expresses high levels of receptors for estradiol. The actions of estradiol on developing brain are generally permanent and range from establishment of sex differences to pervasive trophic and neuroprotective effects. Cellular end points mediated by estradiol include the following: 1) apoptosis, with estradiol preventing it in some regions but promoting it in others; 2) synaptogenesis, again estradiol promotes in some regions and inhibits in others; and 3) morphometry of neurons and astrocytes. Estradiol also impacts cellular physiology by modulating calcium handling, immediate-early-gene expression, and kinase activity. The specific mechanisms of estradiol action permanently impacting the brain are regionally specific and often involve neuronal/glial cross-talk. The introduction of endocrine disrupting compounds into the environment that mimic or alter the actions of estradiol has generated considerable concern, and the developing brain is a particularly sensitive target. Prostaglandins, glutamate, GABA, granulin, and focal adhesion kinase are among the signaling molecules co-opted by estradiol to differentiate male from female brains, but much remains to be learned. Only by understanding completely the mechanisms and impact of estradiol action on the developing brain can we also understand when these processes go awry. PMID:18195084

  20. The Kupffer Cell Number Affects the Outcome of Living Donor Liver Transplantation from Elderly Donors

    PubMed Central

    Hidaka, Masaaki; Eguchi, Susumu; Takatsuki, Mitsuhisa; Soyama, Akihiko; Ono, Shinichiro; Adachi, Tomohiko; Natsuda, Koji; Kugiyama, Tota; Hara, Takanobu; Okada, Satomi; Imamura, Hajime; Miuma, Satoshi; Miyaaki, Hisamitsu

    2016-01-01

    Background There have been no previous reports how Kupffer cells affect the outcome of living donor liver transplantation (LDLT) with an elderly donor. The aim of this study was to elucidate the influence of Kupffer cells on LDLT. Methods A total of 161 adult recipients underwent LDLT. The graft survival, prognostic factors for survival, and graft failure after LDLT were examined between cases with a young donor (<50, n = 112) and an elderly donor (≥50, N = 49). The Kupffer cells, represented by CD68-positive cell in the graft, were examined in the young and elderly donors. Results In a multivariable analysis, a donor older than 50 years, sepsis, and diabetes mellitus were significant predictors of graft failure after LDLT. The CD68 in younger donors was significantly more expressed than that in elderly donors. The group with a less number of CD68-positive cells in the graft had a significantly poor survival in the elderly donor group and prognostic factor for graft failure. Conclusions The worse outcome of LDLT with elderly donors might be related to the lower number of Kupffer cells in the graft, which can lead to impaired recovery of the liver function and may predispose patients to infectious diseases after LDLT. PMID:27819035

  1. Whole-liver CT texture analysis in colorectal cancer: Does the presence of liver metastases affect the texture of the remaining liver?

    PubMed Central

    Rao, Sheng-Xiang; Lambregts, Doenja MJ; Schnerr, Roald S; van Ommen, Wenzel; van Nijnatten, Thiemo JA; Martens, Milou H; Heijnen, Luc A; Backes, Walter H; Verhoef, Cornelis; Zeng, Meng-Su; Beets, Geerard L

    2014-01-01

    Background Liver metastases limit survival in colorectal cancer. Earlier detection of (occult) metastatic disease may benefit treatment and survival. Objective The objective of this article is to evaluate the potential of whole-liver CT texture analysis of apparently disease-free liver parenchyma for discriminating between colorectal cancer (CRC) patients with and without hepatic metastases. Methods The primary staging CT examinations of 29 CRC patients were retrospectively analysed. Patients were divided into three groups: patients without liver metastases (n = 15), with synchronous liver metastases (n = 10) and metachronous liver metastases within 18 months following primary staging (n = 4). Whole-liver texture analysis was performed by delineation of the apparently non-diseased liver parenchyma (excluding metastases or other focal liver lesions) on portal phase images. Mean grey-level intensity (M), entropy (E) and uniformity (U) were derived with no filtration and different filter widths (0.5 = fine, 1.5 = medium, 2.5 = coarse). Results Mean E1.5 and E2.5 for the whole liver in patients with synchronous metastases were significantly higher compared with the non-metastatic patients (p = 0.02 and p = 0.01). Mean U1.5 and U2.5 were significantly lower in the synchronous metastases group compared with the non-metastatic group (p = 0.04 and p = 0.02). Texture parameters for the metachronous metastases group were not significantly different from the non-metastatic group or synchronous metastases group (p > 0.05), although – similar to the synchronous metastases group – there was a subtle trend towards increased E1.5, E2.5 and decreased U1.5, U2.5 values. Areas under the ROC curve for the diagnosis of synchronous metastatic disease based on the texture parameters E1.5,2.5 and U1.5,2.5 ranged between 0.73 and 0.78. Conclusion Texture analysis of the apparently non-diseased liver holds promise to differentiate between CRC

  2. Estradiol and neurodegenerative oxidative stress.

    PubMed

    Nilsen, Jon

    2008-10-01

    Estradiol is a potent preventative against neurodegenerative disease, in part, by activating antioxidant defense systems scavenging reactive oxygen species, limiting mitochondrial protein damage, improving electron transport chain activity and reducing mitochondrial DNA damage. Estradiol also increases the activity of complex IV of the electron transport chain, improving mitochondrial respiration and ATP production under normal and stressful conditions. However, the high oxidative cellular environment present during neurodegeneration makes estradiol a poor agent for treatment of existing disease. Oxidative stress stimulates the production of the hydroperoxide-dependent hydroxylation of estradiol to the catecholestrogen metabolites, which can undergo reactive oxygen species producing redox cycling, setting up a self-generating toxic cascade offsetting any antioxidant/antiapoptotic effects generated by the parent estradiol. Additional disease-induced factors can further perpetuate this cycle. For example dysregulation of the catecholamine system could alter catechol-O-methyltransferase-catalyzed methylation, preventing removal of redox cycling catecholestrogens from the system enhancing pro-oxidant effects of estradiol.

  3. Fasting and sampling time affect liver gene expression of high-fat diet-fed mice.

    PubMed

    Lee, C Y

    2010-05-01

    Several physiological and biological variables are known to affect peroxisome proliferator-activated receptor (PPAR)-α-dependent signaling pathway and plasma biochemical profiles. However, less is known about the effect of these variables on high-fat diet-fed mice. In a 5-week study, C57BL/6 mice were divided into control (C) and high-fat diet-fed (H) groups, whereby before dissection, each group was subdivided into non-fasted (nC and nH) and a 15-h fasted mice (fC and fH) killed in the early light cycle, and a 15-h fasted mice (eC and eH) killed in the late phase of the light cycle. Liver and blood from the vena cava were collected. Non-fasted nC and nH mice have a marginal difference in their body weight gain, whereas significant differences were found for fasted mice. In nH mice, PPAR-α, acyl-CoA oxidase and insulin-like growth factor-binding protein expressions were significantly elevated, in contrast to fatty acid synthase (Fasn), stearoyl CoA-desaturase (SCD)-1, and elongase (ELOVL)-6 expressions. Fasn was profoundly induced in fH mice, while decreased sterol regulatory-binding protein-1 and SCD-1 were found only in eH mice. Different from the gene expression profiles, plasma total cholesterol level of the eH mice was higher than controls, whereas nH mice have increased plasma non-esterified fatty acids. Only glucose level of the fH mice was higher than that observed for controls. Results showed that fasting and sampling time have significantly affected liver gene expression and plasma biochemical indices of the high-fat diet-treated mice. An overlook in these aspects can cause serious discrepancies in the experimental data and their interpretations.

  4. Liver Diseases

    MedlinePlus

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  5. Central expression and anorectic effect of brain-derived neurotrophic factor are regulated by circulating estradiol levels.

    PubMed

    Zhu, Zheng; Liu, Xian; Senthil Kumar, Shiva Priya Dharshan; Zhang, Jing; Shi, Haifei

    2013-03-01

    Estrogens potently suppress food intake. Compelling evidence suggests that estradiol, the primary form of estrogens, reduces food intake by facilitating other anorectic signals. Brain-derived neurotrophic factor (BDNF), like estradiol, appears to suppress food intake by affecting meal size. We hypothesized that estradiol modulates Bdnf expression and the anorectic effect of BDNF. The first goal was to determine whether Bdnf expression was regulated by endogenous estradiol of cycling rats and by cyclic estradiol treatment using ovariectomized rats. Bdnf expression within the ventromedial nucleus of hypothalamus (VMH) was temporally elevated at estrus following the estradiol peak, which coincided with the decline in feeding at this phase of the ovarian cycle. Additionally, food intake and body weight were increased following ovariectomy with a parallel decrease in Bdnf expression in the VMH. All of these alterations were reversed by cyclic estradiol treatment, suggesting that Bdnf expression within the VMH was regulated in an estradiol-dependent manner. The second goal was to determine whether estradiol modulates the anorectic effect of BDNF. Sham-operated estrous rats and ovariectomized rats cyclically treated with estradiol responded to a lower dose of central administration of BDNF to decrease food intake than male rats and oil-treated ovariectomized rats, implying that endogenous estradiol or cyclic estradiol replacement increased the sensitivity to anorectic effect of BDNF. These data indicate that Bdnf expression within the VMH and the anorectic effect of BDNF varied depending on plasma estradiol levels, suggesting that estradiol may regulate BDNF signaling to regulate feeding.

  6. Estradiol reduces dendritic spine density in the ventral striatum of female Syrian hamsters.

    PubMed

    Staffend, Nancy A; Loftus, Caroline M; Meisel, Robert L

    2011-01-01

    Estradiol affects a variety of brain regions by modulating physiological and cellular functions as well as neuronal morphology. Within the striatum, estradiol is known to induce physiological and molecular changes, yet estradiol's effects on striatal dendritic morphology have not yet been evaluated. Using ballistic delivery of the lipophilic dye DiI to tissue sections, we were able to evaluate estradiol's effects on striatal morphology in female Syrian hamsters. We found that estradiol significantly decreased spine density within the nucleus accumbens core, with no effect in the nucleus accumbens shell or caudate. Interestingly, estradiol treatment caused a significant deconstruction of spines from more to less mature spine subtypes in both the nucleus accumbens core and shell regardless of changes in spine density. These results are significant in that they offer a novel mechanism for estradiol actions on a wide variety of nucleus accumbens functions such as motivation or reward as well as their pathological consequences (e.g. drug addiction).

  7. Portal hypertension in polycystic liver disease patients does not affect wait-list or immediate post-liver transplantation outcomes

    PubMed Central

    Rajoriya, Neil; Tripathi, Dhiraj; Leithead, Joanna A; Gunson, Bridget K; Lord, Sophie; Ferguson, James W; Hirschfield, Gideon M

    2016-01-01

    AIM To establish the impact of portal hypertension (PH) on wait-list/post-transplant outcomes in patients with polycystic liver disease (PCLD) listed for liver transplantation. METHODS A retrospective single-centre case controlled study of consecutive patients listed for liver transplantation over 12 years was performed from our centre. PH in the PCLD cohort was defined by the one or more of following parameters: (1) presence of radiological or endoscopic documented varices from our own centre or the referral centre; (2) splenomegaly (> 11 cm) on radiology in absence of splenic cysts accounting for increased imaging size; (3) thrombocytopenia (platelets < 150 × 109/L); or (4) ascites without radiological evidence of hepatic venous outflow obstruction from a single cyst. RESULTS Forty-seven PCLD patients (F: M = 42: 5) were listed for liver transplantation (LT) (single organ, n = 35; combined liver-kidney transplantation, n = 12) with 19 patients (40.4%) having PH. When comparing the PH group with non-PH group, the mean listing age (PH group, 50.6 (6.4); non-PH group, 47.1 (7.4) years; P = 0.101), median listing MELD (PH group, 12; non-PH group, 11; P = 0.422) median listing UKELD score (PH group, 48; non-PH group, 46; P = 0.344) and need for renal replacement therapy (P = 0.317) were similar. In the patients who underwent LT alone, there was no difference in the duration of ICU stay (PH, 3 d; non-PH, 2 d; P = 0.188), hospital stay length (PH, 9 d; non-PH, 10 d; P = 0.973), or frequency of renal replacement therapy (PH, 2/8; non-PH, 1/14; P = 0.121) in the immediate post-transplantation period. CONCLUSION Clinically apparent portal hypertension in patients with PCLD listed for liver transplantation does not appear to have a major impact on wait-list or peri-transplant morbidity. PMID:28018103

  8. Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver.

    PubMed

    Atger, Florian; Gobet, Cédric; Marquis, Julien; Martin, Eva; Wang, Jingkui; Weger, Benjamin; Lefebvre, Grégory; Descombes, Patrick; Naef, Felix; Gachon, Frédéric

    2015-11-24

    Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5'-Terminal Oligo Pyrimidine tract (5'-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5'-UTR (TISU) motif. The increased translation efficiency of 5'-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation.

  9. Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver

    PubMed Central

    Atger, Florian; Gobet, Cédric; Marquis, Julien; Martin, Eva; Wang, Jingkui; Weger, Benjamin; Lefebvre, Grégory; Descombes, Patrick; Naef, Felix; Gachon, Frédéric

    2015-01-01

    Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. Although rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light–dark conditions and ad libitum or night-restricted feeding in WT and brain and muscle Arnt-like 1 (Bmal1)-deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic gene expression, Bmal1 deletion affecting surprisingly both transcriptional and posttranscriptional levels. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5′-Terminal Oligo Pyrimidine tract (5′-TOP) sequences and for genes involved in mitochondrial activity, many harboring a Translation Initiator of Short 5′-UTR (TISU) motif. The increased translation efficiency of 5′-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion also affects amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. PMID:26554015

  10. 3,3 diindolylmethane leads to apoptosis, decreases sperm quality, affects blood estradiol 17 β and testosterone, oestrogen (α and β) and androgen receptor levels in the reproductive system in male rats.

    PubMed

    Aksu, E H; Akman, O; Ömür, A D; Karakuş, E; Can, I; Kandemir, F M; Dorman, E; Uçar, Ö

    2016-12-01

    3,3 Diindolylmethane (DIM) is a major digestive product of indole-3 carbinol, obtained from Brassica family vegetables such as broccoli, cabbage and Brussels sprouts. This study aimed to investigate the effects of DIM on sperm parameters, histological structures of testicular tissues, blood testosterone (T) and estradiol 17-β (E2) in male rats. Thirty-eight male Sprague Dawley rats were used. Rats were divided into four groups: Group I: referred as Control group, received corn oil only; Group II: as DIM-10, rats received 10 mg kg(-1) DIM; Group III: as DIM-50, rats received 50 mg kg(-1) DIM; Group IV: as DIM-100, received 100 mg kg(-1) DIM during 53 days. Spermatological parameters, malondialdehyde (MDA) levels of testes and serum T and E2 levels were assayed. Histopathological examinations of tests were done. DIM caused an increase in MDA levels. It decreased motility and live sperm rates and increased degeneration of testicular tissues. While DIM-10 did not affect abnormal sperm rate, higher concentrations increased the abnormalities. Sperm density was higher in DIM-10 groups when compared to both other groups. Only DIM-50 had an anti-androgenic effect among all groups. Only, DIM-10 showed anti-estrogenic activity as compared to higher DIM groups. In conclusion, DIM (i) had side effect on some sperm characteristics, (ii) increased the MDA levels and (iii) led to histological degeneration of testicular tissues and apoptosis in a dose-dependent manner.

  11. Genetic factors affecting gene transcription and catalytic activity of UDP-glucuronosyltransferases in human liver.

    PubMed

    Liu, Wanqing; Ramírez, Jacqueline; Gamazon, Eric R; Mirkov, Snezana; Chen, Peixian; Wu, Kehua; Sun, Chang; Cox, Nancy J; Cook, Edwin; Das, Soma; Ratain, Mark J

    2014-10-15

    The aim of this study was to discover cis- and trans-acting factors significantly affecting mRNA expression and catalytic activity of human hepatic UDP-glucuronosyltransferases (UGTs). Transcription levels of five major hepatic UGT1A (UGT1A1, UGT1A3, UGT1A4, UGT1A6 and UGT1A9) and five UGT2B (UGT2B4, UGT2B7, UGT2B10, UGT2B15 and UGT2B17) genes were quantified in human liver tissue samples (n = 125) using real-time PCR. Glucuronidation activities of 14 substrates were measured in 47 livers. We genotyped 167 tagSNPs (single-nucleotide polymorphisms) in UGT1A (n = 43) and UGT2B (n = 124), as well as the known functional UGT1A1*28 and UGT2B17 CNV (copy number variation) polymorphisms. Transcription levels of 15 transcription factors (TFs) known to regulate these UGTs were quantified. We found that UGT expression and activity were highly variable among the livers (median and range of coefficient of variations: 135%, 74-217% and 52%, 39-105%, respectively). CAR, PXR and ESR1 were found to be the most important trans-regulators of UGT transcription (median and range of correlation coefficients: 46%, 6-58%; 47%, 9-58%; and 52%, 24-75%, respectively). Hepatic UGT activities were mainly determined by UGT gene transcription levels. Twenty-one polymorphisms were significantly (FDR-adjusted P < 0.05) associated with mRNA expression and/or activities of UGT1A1, UGT1A3 and UGT2B17. We found novel SNPs in the UGT2B17 CNV region accounting for variability in UGT2B17 gene transcription and testosterone glucuronidation rate, in addition to that attributable to the UGT2B17 CNV. Our study discovered novel pharmacogenetic markers and provided detailed insight into the genetic network regulating hepatic UGTs.

  12. Cognitive flexibility but not cognitive coordination is affected in rats with toxic liver failure.

    PubMed

    Wesierska, Malgorzata; Klinowska, Hanna D; Adamska, Iwona; Fresko, Inez; Sadowska, Joanna; Albrecht, Jan

    2006-07-15

    Hepatic encephalopathy (HE), a consequence of liver damage, is associated with cognitive deficits. In this study, behavioral activity, non-associative learning, associative memory, cognitive coordination and flexibility were investigated in rats with subclinical HE evoked by thioacetamide treatment. Non-associative learning was studied in the open field (OF) set up in 12 HE and 8 saline-injected control rats (C). Memory was examined in spatial place avoidance tasks in 10 HE and 10 C rats. The Room+ Arena- task involved the selection of distal room stimuli from irrelevant arena stimuli (i.e. intramaze cues and/or self-motion information), which engages processes of cognitive coordination. Following the Room+ Arena- training, cognitive flexibility of rats was tested in the Arena+ place avoidance condition, which demands the previously ignored stimuli from arena. In the OF test HE and control rats behaved similar. They displayed high activity in the first block of each session and this pattern was stable. In both groups of rats darkness enhanced locomotor activity in comparison to light only in the first block. The HE and C rats avoided the to-be-avoided place in the Room+ Arena- task, whereas only HE rats were affected in the Arena+ task. In conclusion, these results demonstrate cognitive inflexibility in HE rats. We suggest that (1) the behavioral changes in the TAA model are typical of subclinical HE and (2) test for cognitive flexibility may be modified towards a routine use in patients with subclinical HE.

  13. Tauroursodeoxycholic acid affects PPARγ and TLR4 in Steatotic liver transplantation.

    PubMed

    Jiménez-Castro, M B; Elias-Miro, M; Mendes-Braz, M; Lemoine, A; Rimola, A; Rodés, J; Casillas-Ramírez, A; Peralta, C

    2012-12-01

    Numerous steatotic livers are discarded for transplantation because of their poor tolerance to ischemia-reperfusion (I/R). We examined whether tauroursodeoxycholic acid (TUDCA), a known inhibitor of endoplasmic reticulum (ER) stress, protects steatotic and nonsteatotic liver grafts preserved during 6 h in University of Wisconsin (UW) solution and transplanted. The protective mechanisms of TUDCA were also examined. Neither unfolded protein response (UPR) induction nor ER stress was evidenced in steatotic and nonsteatotic liver grafts after 6 h in UW preservation solution. TUDCA only protected steatotic livers grafts and did so through a mechanism independent of ER stress. It reduced proliferator-activated receptor-γ (PPARγ) and damage. When PPARγ was activated, TUDCA did not reduce damage. TUDCA, which inhibited PPARγ, and the PPARγ antagonist treatment up-regulated toll-like receptor 4 (TLR4), specifically the TIR domain-containing adaptor inducing IFNβ (TRIF) pathway. TLR4 agonist treatment reduced damage in steatotic liver grafts. When TLR4 action was inhibited, PPARγ antagonists did not protect steatotic liver grafts. In conclusion, TUDCA reduced PPARγ and this in turn up-regulated the TLR4 pathway, thus protecting steatotic liver grafts. TLR4 activating-based strategies could reduce the inherent risk of steatotic liver failure after transplantation.

  14. Treatment with Oxidized Phospholipids Directly Inhibits Nonalcoholic Steatohepatitis and Liver Fibrosis Without Affecting Steatosis.

    PubMed

    Mendel, Itzhak; Yacov, Niva; Shoham, Anat; Ishai, Eti; Breitbart, Eyal

    2016-09-01

    Previous studies demonstrated that toll-like receptors 4 and 2 (TLR-4 and TLR-2), which are expressed on liver-resident Kupffer, hepatic stellate cells, and circulating monocytes, play a role in nonalcoholic fatty liver disease. Lecinoxoids are oxidized phospholipids that antagonize TLR-2- and TLR-4-mediated activation of innate immune cells and inhibit monocyte migration. In this study, we tested the effect of two functionally different lecinoxoids on the development of nonalcoholic steatohepatitis and liver fibrosis in a mouse model. Two-day-old C57BL/6 mice were injected with streptozotocin and fed a high-fat diet from Week 4 after birth. At Week 6 post-birth, lecinoxoids VB-201 or VB-703 were given orally, once daily, for 3 weeks. Telmisartan was administered orally, once daily, for 3 weeks, as positive control. At experiment conclusion, biochemical indices were evaluated. HE stain and quantitative PCR were used to determine the extent of steatosis and steatohepatitis, and Sirius red stain was used to assess liver fibrosis. Treatment with lecinoxoids did not alter the concentration of blood glucose, liver triglycerides, or steatosis compared with solvent-treated mice. However, whereas VB-201 inhibited the development of fibrosis and, to some extent, liver inflammation, VB-703 significantly lessened both liver inflammation and fibrosis. This study indicates that using lecinoxoids to antagonize TLR-2, and more prominently TLR-4, is sufficient to significantly inhibit nonalcoholic steatohepatitis and liver fibrosis. Inhibiting monocyte migration with lecinoxoids that are relatively weak TLR-4 antagonists may alter liver fibrosis and to some extent nonalcoholic steatohepatitis.

  15. Acute exposure of a glyphosate-based herbicide affects the gills and liver of the Neotropical fish, Piaractus mesopotamicus.

    PubMed

    Shiogiri, Natália S; Paulino, Marcelo G; Carraschi, Silvia P; Baraldi, Flávia G; da Cruz, Claudinei; Fernandes, Marisa Narciso

    2012-09-01

    The aim of this study was to determine the acute toxicity of Roundup(®) Ready (RR) in Piaractus mesopotamicus, and evaluate the effects on the morphology of the gills and liver of exposed surviving fish. Fish were exposed to 3.0, 3.5, 4.0 and 4.5mgL(-1) of glyphosate, and the LC(50);48h was estimated at 3.74±0.2mgL(-1). Gill histopathology was rare, and the activity of Na(+)/K(+)-ATPase enzyme did not change, suggesting normal function. However, the damage to the liver was classified as moderate to severe. Cytoplasmic vacuolization, lipid accumulation, nuclear and cellular membrane alterations and glycogen depletion were found in the liver, suggesting a reduction in the liver function. The glyphosate in the RR formulation was classified as moderately toxic for P. mesopotamicus, and the severe damage in the liver may affect the detoxification and/or tissue repair process and contribute to fish death.

  16. Geographic inequities in liver allograft supply and demand: does it affect patient outcomes?

    PubMed

    Rana, Abbas; Kaplan, Bruce; Riaz, Irbaz B; Porubsky, Marian; Habib, Shahid; Rilo, Horacio; Gruessner, Angelika C; Gruessner, Rainer W G

    2015-03-01

    Significant geographic inequities mar the distribution of liver allografts for transplantation. We analyzed the effect of geographic inequities on patient outcomes. During our study period (January 1 through December 31, 2010), 11,244 adult candidates were listed for liver transplantation: 5,285 adult liver allografts became available, and 5,471 adult recipients underwent transplantation. We obtained population data from the 2010 United States Census. To determine the effect of regional supply and demand disparities on patient outcomes, we performed linear regression and multivariate Cox regression analyses. Our proposed disparity metric, the ratio of listed candidates to liver allografts available varied from 1.3 (region 11) to 3.4 (region 1). When that ratio was used as the explanatory variable, the R(2) values for outcome measures were as follows: 1-year waitlist mortality, 0.23 and 1-year posttransplant survival, 0.27. According to our multivariate analysis, the ratio of listed candidates to liver allografts available had a significant effect on waitlist survival (hazards ratio, 1.21; 95% confidence interval, 1.04-1.40) but was not a significant risk factor for posttransplant survival. We found significant differences in liver allograft supply and demand--but these differences had only a modest effect on patient outcomes. Redistricting and allocation-sharing schemes should seek to equalize regional supply and demand rather than attempting to equalize patient outcomes.

  17. Liver condition of Holstein cows affects mitochondrial function and fertilization ability of oocytes.

    PubMed

    Tanaka, Hiroshi; Takeo, Shun; Abe, Takahito; Kin, Airi; Shirasuna, Koumei; Kuwayama, Takehito; Iwata, Hisataka

    2016-06-17

    The aim of the present study was to examine the fertilization ability and mitochondrial function of oocytes derived from cows with or without liver damage. Oocytes were collected from the ovaries of cows with damaged livers (DL) and those of cows with healthy livers (HL), subjected to in vitro maturation, and fertilized in vitro. A significantly high abnormal fertilization rate was observed for oocytes from DL cows compared to oocytes from HL cows. The time to dissolve the zona pellucida by protease before fertilization was similar between the two liver conditions, whereas after fertilization treatment this time was shorter for DL cows than for HL cows. The percentage of oocytes with equivalent cortical granule distributions underneath the membrane was greater for in vitro matured oocytes from HL cows, whereas an immature distribution pattern was observed for oocytes from DL cows. In addition, a greater percentage of oocytes derived from HL cows released cortical granules following fertilization compared with oocytes from DL cows. Mitochondrial function determined by ATP content and membrane potential were similar at the germinal vesicle stage, but post-in vitro maturation, the oocytes derived from HL cows showed higher values than DL cows. The mitochondrial DNA copy number in oocytes was similar between the two liver conditions for both the germinal vesicle and post-in vitro maturation oocytes. In conclusion, liver damage induces low fertilization, likely because of incomplete cortical granule distribution and release, and the maturation of oocytes from DL cows contain low-functioning mitochondria compared to their HL counterparts.

  18. Factors Affecting Health-Related Quality of Life and Physical Activity after Liver Transplantation for Autoimmune and Nonautoimmune Liver Diseases: A Prospective, Single Centre Study

    PubMed Central

    Kotarska, Katarzyna; Kempińska-Podhorodecka, Agnieszka; Raszeja-Wyszomirska, Joanna; Bogdanos, Dimitrios P.; Wójcicki, Maciej; Milkiewicz, Piotr

    2014-01-01

    Background/Aim. With the improvement of the outcomes after liver transplantation (LTx), health-related quality of life (HRQoL) and physical activity are becoming significant outcome parameters. We prospectively assessed these parameters in patients with autoimmune and nonautoimmune liver disorders undergoing LTx. Materials and Methods. Patients (n = 107) were subdivided into 3 groups depending on the time after LTx: group-A (n = 21): 6–12 months; group-B (n = 48): 13–36 months; and group-C (n = 38): >37 months. SF-36 and IPAQ were applied in HRQoL and physical activity assessment. Results. Females had impaired HRQoL in most SF-36 domains. Younger patients showed higher scores at SF-36 physical functioning domain but IPAQ was not influenced by age. Group-B had higher general health and physical component summary than group-A (P = 0.037, P = 0.04, resp.) and total IPAQ than group-C (P = 0.047). The sitting time domain was longer in group-A than in group-B and group-C (P = 0.0157;  P = 0.042, resp.). Employed patients had better HRQoL and higher physical activity than those not working. SF-36 and IPAQ were unrelated to the autoimmune etiology of liver disease. Conclusions. These findings show that female and unemployed patients have worse HRQoL, while gender and age at LTx time do not affect IPAQ's physical activity. The autoimmune etiology of liver disease does not influence HRQoL and physical activity after LTx. PMID:24741621

  19. Estradiol's effects on learning and neuronal morphology vary with route of administration.

    PubMed

    Garza-Meilandt, Annette; Cantu, Rebecca E; Claiborne, Brenda J

    2006-08-01

    Estrogen's effects on performance and neuronal morphology are variable, and the reasons for this variability are not yet understood. In this study, the authors compared the effects of 2 delivery routes of 17 beta-estradiol on spatial learning and dendritic spine densities in young ovariectomized rats; estradiol was administered by implanted capsules or by daily oral gavage. Estradiol treatment via capsules improved performance in the radial-arm water maze and increased spine densities on dendrites of CA1 pyramidal neurons in the hippocampal formation. In contrast, daily oral administration of estradiol did not affect either measure. These data demonstrate that estradiol delivery is a critical variable in animal studies and that clinical studies comparing the effects of different estradiol treatment routes on cognition are warranted. Copyright 2006 APA, all rights reserved.

  20. Unsaturated fatty acids and sodium affect the liver-like off-flavor in cooked beef.

    PubMed

    Jenschke, B E; Hodgen, J M; Meisinger, J L; Hamling, A E; Moss, D A; Lundesjö Ahnström, M; Eskridge, K M; Calkins, C R

    2007-11-01

    Beef knuckles (n = 60) were chosen from a population of 328 knuckles to test a selection procedure and determine the potential causes of liver-like off-flavor. In phase I, 2 independent panelists were allowed to smell the aromas or smell and taste samples of cooked beef to determine the presence or absence of the liver-like off-flavor and off-flavor intensity. The panelists tested knuckles from 5 feedlots, but only identified 29 as having an off-flavor. A kappa statistic was generated to assess the level of agreement of the 2 panelists that indicated the panelists moderately or substantially agreed when judgments were based on smell exclusively or smelling and tasting, respectively. Although the agreement was acceptable (kappa = 0.57 and 0.76), there was not enough variation in the liver-like off-flavor and off-flavor intensity for the 2 panelists to detect differences compared with an independent sensory panel. Phase II identified factors that led to the development of the liver-like off-flavor in beef. The M. rectus femoris from knuckles identified from phase I were used. Sensory analysis, proximate composition, heme iron, mineral content, and fatty acid analyses were conducted. Stepwise regression was used to identify factors contributing to the liver-like off-flavor. Specifically, Na, 16:1, cis 18:1(n-7), 20:2(n-6), and 20:3(n-6) fatty acids explained (P = 0.021) 46% of the variation of the liver-like off-flavor. Although previously reported as playing a role in the development of the liver-like off-flavor, iron, heme iron, and pH had no effect in this study.

  1. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

    PubMed

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-26

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

  2. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour

    PubMed Central

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-01

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects. We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model. Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males. PMID:26678032

  3. Obstructive sleep apnea syndrome affects liver histology and inflammatory cell activation in pediatric nonalcoholic fatty liver disease, regardless of obesity/insulin resistance.

    PubMed

    Nobili, Valerio; Cutrera, Renato; Liccardo, Daniela; Pavone, Martino; Devito, Rita; Giorgio, Valentina; Verrillo, Elisabetta; Baviera, Giuseppe; Musso, Giovanni

    2014-01-01

    Obstructive sleep apnea syndrome (OSAS) and nonalcoholic fatty liver disease (NAFLD) are frequently encountered in obese children. Whether OSAS and intermittent hypoxia are associated with liver injury in pediatric NAFLD is unknown. To assess the relationship of OSAS with liver injury in pediatric NAFLD. Sixty-five consecutive children with biopsy-proven NAFLD (age, mean ± SD, 11.7 ± 2.1 yr; 58% boys; body mass index z score, 1.93 ± 0.61) underwent a clinical-biochemical assessment and a standard polysomnography. Insulin sensitivity, circulating proinflammatory cytokines, markers of hepatocyte apoptosis (cytokeratin-18 fragments), and hepatic fibrogenesis (hyaluronic acid) were measured. Liver inflammatory infiltrate was characterized by immunohistochemistry for CD45, CD3, and CD163, surface markers of leukocytes, T cells, and activated macrophage/Kupffer cells, respectively. OSAS was defined by an apnea/hypopnea index (AHI) greater than or equal to 1 event/h, and severe OSAS was defined by an AHI greater than or equal to 5 events/h. Fifty-five percent of children with NAFLD had nonalcoholic steatohepatitis (NASH), and 34% had significant (stage F ≥ 2) fibrosis. OSAS affected 60% of children with NAFLD; the presence and severity of OSAS were associated with the presence of NASH (odds ratio, 4.89; 95% confidence interval, 3.08-5.98; P = 0.0001), significant fibrosis (odds ratio, 5.91; 95% confidence interval, 3.23-7.42; P = 0.0001), and NAFLD activity score (β, 0.347; P = 0.029), independently of body mass index, abdominal adiposity, metabolic syndrome, and insulin resistance. This relationship held also in nonobese children with NAFLD. The duration of hemoglobin desaturation (Sa(O2) < 90%) correlated with increased intrahepatic leukocytes and activated macrophages/Kupffer cells and with circulating markers of hepatocyte apoptosis and fibrogenesis. In pediatric NAFLD, OSAS is associated with biochemical, immunohistochemical, and histological features of NASH

  4. [Research on cytokines gene express of rats alcoholic liver disease affected by tea polyphenol].

    PubMed

    Zhang, Xing-Guo; Yu, Chao-Hui; Jiang, Qi; Zhang, Yu; Chen, Shao-Hua; Lu, You-Ming

    2005-06-01

    To evaluate the effect of tea polyphenol(TP) on the rat with alcoholic liver damage. Rats were divided into 3 groups, in which 2 groups were stomach perfused with alcohol to result in ALD, and 1 group of them stomach perfused with TP simultaneously. Another group was normal control groups (stomach perfused with drinking water). In the end of 12 weeks, the liver specimen of each rat was observed by anglicizing its tissue damage, and all data collected was performed by statistical analysis in quantum and semi-quantum. Meanwhile cytokines gene express of each group is determined. In the end of 12 weeks, alcoholic hepatitis appeared in rat liver. Hepatic injury in alcohol group and TP group were found, but could not be found in normal group. Compared with pure alcohol group, alcoholic liver damage mainly showing with steatosis in TP group were slight, in addition showing liver cellular swelling with small area, with less spot and focal necrosis, none bridging necrosis. Steatosis were slight relatively, mega-bubble steatosis were less found. Collagen deposition of TP group were less than those of pure alcohol group. Gene expression of. cytokine have diversity statistically such as IL-3, IL-4, IL-1R2, IL-6R, IL-7R2, IL-3Ra, IL-R1, IL-13, IL-1R1, IL-7R2, EPO-R, LIFR, IL-1R2, IL-5R2, CSF1, CD27, IL-6R. TP is able to attenuate alcoholic liver damage. It's mechanism is possibly due to modulating cytokines gene expression of cytokine.

  5. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

    DOE PAGES

    Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; ...

    2014-06-10

    HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). Amore » biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver disease (εmax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.« less

  6. Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

    SciTech Connect

    Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; Conway, Jessica M.; Crespo, Gonzalo; Navasa, Miquel; D’Amato, Massimo; Ferenci, Peter; Cotler, Scott J.; Forns, Xavier; Perelson, Alan S.; Dahari, Harel

    2014-06-10

    HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. Our results show that baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver disease (εmax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). The 2nd phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, SE=0.18/day]). HCV-infected cell loss rate (δ[SE]=0.62/day[0.05/day]) was high and similar among groups. We conclude that the high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.

  7. Liver condition of Holstein cows affects mitochondrial function and fertilization ability of oocytes

    PubMed Central

    TANAKA, Hiroshi; TAKEO, Shun; ABE, Takahito; KIN, Airi; SHIRASUNA, Koumei; KUWAYAMA, Takehito; IWATA, Hisataka

    2016-01-01

    The aim of the present study was to examine the fertilization ability and mitochondrial function of oocytes derived from cows with or without liver damage. Oocytes were collected from the ovaries of cows with damaged livers (DL) and those of cows with healthy livers (HL), subjected to in vitro maturation, and fertilized in vitro. A significantly high abnormal fertilization rate was observed for oocytes from DL cows compared to oocytes from HL cows. The time to dissolve the zona pellucida by protease before fertilization was similar between the two liver conditions, whereas after fertilization treatment this time was shorter for DL cows than for HL cows. The percentage of oocytes with equivalent cortical granule distributions underneath the membrane was greater for in vitro matured oocytes from HL cows, whereas an immature distribution pattern was observed for oocytes from DL cows. In addition, a greater percentage of oocytes derived from HL cows released cortical granules following fertilization compared with oocytes from DL cows. Mitochondrial function determined by ATP content and membrane potential were similar at the germinal vesicle stage, but post-in vitro maturation, the oocytes derived from HL cows showed higher values than DL cows. The mitochondrial DNA copy number in oocytes was similar between the two liver conditions for both the germinal vesicle and post-in vitro maturation oocytes. In conclusion, liver damage induces low fertilization, likely because of incomplete cortical granule distribution and release, and the maturation of oocytes from DL cows contain low-functioning mitochondria compared to their HL counterparts. PMID:26832309

  8. Methylation of the chicken vitellogenin gene: influence of estradiol administration.

    PubMed Central

    Meijlink, F C; Philipsen, J N; Gruber, M; Ab, G

    1983-01-01

    The degree of methylation of the chicken vitellogenin gene has been investigated. Upon induction by administration of estradiol to a rooster, methyl groups at specific sites near the 5'-end of the gene are eliminated. The process of demethylation is slower than the activation of the gene. Demethylation is therefore probably not a prerequisite to gene transcription. At least two other sites in the coding region of the gene are methylated in the liver of estrogenized roosters, but not in the liver of a laying hen, where the gene is naturally active. Images PMID:6298743

  9. Folate supplementation differently affects uracil content in DNA in the mouse colon and liver

    USDA-ARS?s Scientific Manuscript database

    High folate intake may increase the risk of cancer, especially in the elderly. The present study examined the effects of ageing and dietary folate on uracil misincorporation into DNA, which has a mutagenic effect, in the mouse colon and liver. Old (18 months; n 42) and young (4 months; n 42) male C5...

  10. Re-adaption on Earth after Spaceflights Affects the Mouse Liver Proteome.

    PubMed

    Anselm, Viktoria; Novikova, Svetlana; Zgoda, Victor

    2017-08-12

    Harsh environmental conditions including microgravity and radiation during prolonged spaceflights are known to alter hepatic metabolism. Our studies have focused on the analysis of possible changes in metabolic pathways in the livers of mice from spaceflight project "Bion-M 1". Mice experienced 30 days of spaceflight with and without an additional re-adaption period of seven days compared to control mice on Earth. To investigate mice livers we have performed proteomic profiling utilizing shotgun mass spectrometry followed by label-free quantification. Proteomic data analysis provided 12,206 unique peptides and 1,086 identified proteins. Label-free quantification using MaxQuant software followed by multiple sample statistical testing (ANOVA) revealed 218 up-regulated and 224 down-regulated proteins in the post-flight compared to the other groups. Proteins related to amino acid metabolism showed higher levels after re-adaption, which may indicate higher rates of gluconeogenesis. Members of the peroxisome proliferator-activated receptor pathway reconstitute their level after seven days based on a decreased level in comparison with the flight group, which indicates diminished liver lipotoxicity. Moreover, bile acid secretion may regenerate on Earth due to reconstitution of related transmembrane proteins and CYP superfamily proteins elevated levels seven days after the spaceflight. Thus, our study demonstrates reconstitution of pharmacological response and decreased liver lipotoxicity within seven days, whereas glucose uptake should be monitored due to alterations in gluconeogenesis.

  11. Re-Adaption on Earth after Spaceflights Affects the Mouse Liver Proteome

    PubMed Central

    Anselm, Viktoria; Novikova, Svetlana; Zgoda, Victor

    2017-01-01

    Harsh environmental conditions including microgravity and radiation during prolonged spaceflights are known to alter hepatic metabolism. Our studies have focused on the analysis of possible changes in metabolic pathways in the livers of mice from spaceflight project “Bion-M 1”. Mice experienced 30 days of spaceflight with and without an additional re-adaption period of seven days compared to control mice on Earth. To investigate mice livers we have performed proteomic profiling utilizing shotgun mass spectrometry followed by label-free quantification. Proteomic data analysis provided 12,206 unique peptides and 1086 identified proteins. Label-free quantification using MaxQuant software followed by multiple sample statistical testing (ANOVA) revealed 218 up-regulated and 224 down-regulated proteins in the post-flight compared to the other groups. Proteins related to amino acid metabolism showed higher levels after re-adaption, which may indicate higher rates of gluconeogenesis. Members of the peroxisome proliferator-activated receptor pathway reconstitute their level after seven days based on a decreased level in comparison with the flight group, which indicates diminished liver lipotoxicity. Moreover, bile acid secretion may regenerate on Earth due to reconstitution of related transmembrane proteins and CYP superfamily proteins elevated levels seven days after the spaceflight. Thus, our study demonstrates reconstitution of pharmacological response and decreased liver lipotoxicity within seven days, whereas glucose uptake should be monitored due to alterations in gluconeogenesis. PMID:28805685

  12. Postnatal hyperoxia exposure differentially affects hepatocytes and liver haemopoietic cells in newborn rats.

    PubMed

    Marconi, Guya Diletta; Zara, Susi; De Colli, Marianna; Di Valerio, Valentina; Rapino, Monica; Zaramella, Patrizia; Dedja, Arben; Macchi, Veronica; De Caro, Raffaele; Porzionato, Andrea

    2014-01-01

    Premature newborns are frequently exposed to hyperoxic conditions and experimental data indicate modulation of liver metabolism by hyperoxia in the first postnatal period. Conversely, nothing is known about possible modulation of growth factors and signaling molecules involved in other hyperoxic responses and no data are available about the effects of hyperoxia in postnatal liver haematopoiesis. The aim of the study was to analyse the effects of hyperoxia in the liver tissue (hepatocytes and haemopoietic cells) and to investigate possible changes in the expression of Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinase 9 (MMP-9), Hypoxia-Inducible Factor-1α (HIF-1α), endothelial Nitric Oxide Synthase (eNOS), and Nuclear Factor-kB (NF-kB). Experimental design of the study involved exposure of newborn rats to room air (controls), 60% O2 (moderate hyperoxia), or 95% O2 (severe hyperoxia) for the first two postnatal weeks. Immunohistochemical and Western blot analyses were performed. Severe hyperoxia increased hepatocyte apoptosis and MMP-9 expression and decreased VEGF expression. Reduced content in reticular fibers was found in moderate and severe hyperoxia. Some other changes were specifically produced in hepatocytes by moderate hyperoxia, i.e., upregulation of HIF-1α and downregulation of eNOS and NF-kB. Postnatal severe hyperoxia exposure increased liver haemopoiesis and upregulated the expression of VEGF (both moderate and severe hyperoxia) and eNOS (severe hyperoxia) in haemopoietic cells. In conclusion, our study showed different effects of hyperoxia on hepatocytes and haemopoietic cells and differential involvement of the above factors. The involvement of VEGF and eNOS in the liver haemopoietic response to hyperoxia may be hypothesized.

  13. Exercise training attenuates anaphylactic venoconstriction in rat perfused liver, but does not affect anaphylactic hypotension in conscious rats.

    PubMed

    Cui, Sen; Shibamoto, Toshishige; Zhang, Wei; Kurata, Yasutaka; Kashimura, Osamu; Miyamae, Shunichi

    2010-09-01

    1. Exercise training attenuates circulatory shock due to haemorrhage, endotoxin or heatstroke. However, it remains unknown whether exercise training attenuates anaphylactic shock. Hepatic venoconstriction is involved in rat anaphylactic hypotension. In the present study, we determined the effects of exercise training on both anaphylaxis-induced segmental venoconstriction in rat perfused livers and systemic anaphylaxis in conscious rats. The role of nitric oxide (NO) in the effect of exercise on the venoconstriction of perfused livers was also examined. 2. Rats were subjected to running training on a motorized treadmill for 4 weeks. Two weeks prior to the anaphylaxis experiment, Sprague-Dawley rats were actively sensitized with the antigen ovalbumin. In isolated livers perfused portally with blood, the portal venous pressure (P(pv)) and sinusoidal pressure were measured to determine the pre- and post-sinusoidal resistances (R(pre) and R(post), respectively). In conscious rats, systemic arterial pressure (SAP) and P(pv) were determined. 3. In the perfused livers of sedentary rats, antigen administration led to a predominant presinusoidal constriction, as evidenced by 4.6- and 1.7-fold increases in R(pre) and R(post), respectively. The anaphylaxis-induced increase in R(pre) was significantly attenuated by 24% by exercise training. Inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester (100 micromol/L) 10 min prior to the injection of antigen enhanced anaphylactic venoconstriction, but did not alter the effect of exercise training on the increase in R(pre). In contrast, exercise training did not attenuate either anaphylactic hypotension or portal hypertension in conscious rats. 4. In conclusion, exercise training attenuates the anaphylaxis-induced presinusoidal constriction in rat isolated perfused livers, independent of NO production. However, this action is not evident in conscious rats and exercise training does not affect anaphylactic hypotension in

  14. Role of an estradiol regulatory factor-hydroxysteroid dehydrogenase (HSD) in Toxoplasma gondii infection and pathogenicity.

    PubMed

    Zhang, Xiao; Liu, Jing; Li, Muzi; Fu, Yong; Zhang, Taotao; Han, Qian; Liu, Qun

    2017-09-05

    Toxoplasma gondii is an apicomplexan parasite that infects most species of warm-blooded animals, including humans, and causes abortions and severe damage to the fetal central nervous system. During pregnancy, the prevalence of toxoplasmosis increases throughout the second and third quarter of gestation, while the hormones progesterone and estradiol simultaneously increase. Thus, it has been suggested that these hormones could affect parasite reproduction. This study was mainly focused on an estradiol regulatory factor-Hydroxysteroid dehydrogenase (HSD) gene in T. gondii. Our data showed that estradiol promoted Pru (Type II) and VEG (Type III) infection and thus significantly contributed to the pathogenicity of T. gondii in mice. Subsequently, we found that this phenomenon may relate to the interplay of T. gondii and estradiol. We reported that estradiol can enter T. gondii tachyzoites. Bioinformatics analysis showed that T. gondii may have a residual estradiol metabolism-related gene HSD. To verify the gene function, HEK293T cells were transiently transfected with Tg-HSD and gene expression was induced. Then, HPLC (high-performance liquid chromatography) analysis showed that Tg-HSD can efficiently transform estrone into estradiol. Moreover, Tg-HSD -overexpressing parasites showed significantly enhanced pathogenicity and upregulation of estradiol levels in mice. In conclusion, estradiol can promote T. gondii infection in vitro and in vivo, and this may be related to its Tg- HSD gene. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. 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

  16. Colon cancer metastasis in mouse liver is not affected by hypercoagulability due to Factor V Leiden mutation

    PubMed Central

    Klerk, CPW; Smorenburg, SM; Spek, CA; Van Noorden, CJF

    2007-01-01

    Abstract Clinical trials have shown life-prolonging effects of antithrombotics in cancer patients, but the molecular mechanisms remain unknown due to the multitude of their effects. We investigated in a mouse model whether one of the targets of antithrombotic therapy, fibrin deposition, stimulates tumour development. Fibrin may provide either protection of cancer cells in the circulation against mechanical stress and the immune system, or form a matrix for tumours and/or angiogenesis in tumours to develop. Mice homozygous for Factor V Leiden (FVL), a mutation in one of the coagulation factors that facilitates fibrin formation, were used to investigate whether hypercoagulability affects tumour development in an experimental metastasis model. Liver metastases of colon cancer were induced in mice with the FVL mutation and wild-type littermates. At day 21, number and size of tumours at the liver surface, fibrin/fibrinogen distribution, vessel density and the presence of newly formed vessels in tumours were analysed. Number and size of tumours did not differ between mice with and without the FVL mutation. Fibrin/fibrinogen was found in the cytoplasm of hepatocytes and cancer cells, in blood vessels in liver and tumour tissue and diffusely distributed outside vessels in tumours, indicating leaky vessels. Vessel density and angiogenesis varied widely between tumours, but a pre-dominance for vessel-rich or vessel-poor tumours or vessel formation could not be found in either genotype. In conclusion, the FVL mutation has no effect on the development of secondary tumours of colon cancer in livers of mice. Fibrin deposition and thus inhibition of fibrin formation by anticoagulants do not seem to affect tumour development in this model. PMID:17635646

  17. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis

    PubMed Central

    Chun, Sunwoo; Bamba, Takeshi; Suyama, Tatsuya; Ishijima, Tomoko; Fukusaki, Eiichiro; Abe, Keiko; Nakai, Yuji

    2016-01-01

    A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids

  18. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis.

    PubMed

    Chun, Sunwoo; Bamba, Takeshi; Suyama, Tatsuya; Ishijima, Tomoko; Fukusaki, Eiichiro; Abe, Keiko; Nakai, Yuji

    2016-01-01

    A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids

  19. Idiosyncratic drug toxicity affecting the liver, skin, and bone marrow in dogs and cats.

    PubMed

    Trepanier, Lauren A

    2013-09-01

    Idiosyncratic drug toxicity reactions are, by definition, uncommon, but can lead to serious or even fatal organ toxicity. The liver, skin, and peripheral blood cells/bone marrow are common targets. Most of these reactions are the result of reactive metabolites, which may cause local cell or organelle damage, or may be amplified by a systemic immune response. Individual risk may depend on differences in drug biotransformation, levels of oxidative stress, or antigen presentation. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Toll-like receptor 7 affects the pathogenesis of non-alcoholic fatty liver disease.

    PubMed

    Kim, Sokho; Park, Surim; Kim, Bumseok; Kwon, Jungkee

    2016-06-09

    Recently, a possible link between toll-like receptor 7 (TLR7) and liver disease was suggested, although it was limited to fibrosis. Based on this report, we investigated whether TLR7 has a pivotal role in non-alcoholic fatty liver disease (NAFLD). The TLR7 signaling pathway, which is activated by imiquimod (TLR7 ligand) naturally, induced autophagy and released insulin-like growth factor 1 (IGF-1) into medium from hepatocytes. Lipid accumulation induced by unsaturated fatty acid (UFA; arachidonic acid:oleic acid = 1:1) in hepatocytes, was attenuated in TLR7 and autophagy activation. Interestingly, TLR7 activation attenuated UFA-induced lipid peroxidation products, such as malondialdehyde (MDA) and 4-Hydroxy-2-Nonenal (4-HNE). To clarify a possible pathway between TLR7 and lipid peroxidation, we treated hepatocytes with MDA and 4-HNE. MDA and 4-HNE induced 2-folds lipid accumulation in UFA-treated hepatocytes via blockade of the TLR7 signaling pathway's IGF-1 release compared to only UFA-treated hepatocytes. In vivo experiments carried out with TLR7 knockout mice produced results consistent with in vitro experiments. In conclusion, TLR7 prevents progression of NAFLD via induced autophagy and released IGF-1 from liver. These findings suggest a new therapeutic strategy for the treatment of NAFLD.

  1. Toll-like receptor 7 affects the pathogenesis of non-alcoholic fatty liver disease

    PubMed Central

    Kim, Sokho; Park, Surim; Kim, Bumseok; Kwon, Jungkee

    2016-01-01

    Recently, a possible link between toll-like receptor 7 (TLR7) and liver disease was suggested, although it was limited to fibrosis. Based on this report, we investigated whether TLR7 has a pivotal role in non-alcoholic fatty liver disease (NAFLD). The TLR7 signaling pathway, which is activated by imiquimod (TLR7 ligand) naturally, induced autophagy and released insulin-like growth factor 1 (IGF-1) into medium from hepatocytes. Lipid accumulation induced by unsaturated fatty acid (UFA; arachidonic acid:oleic acid = 1:1) in hepatocytes, was attenuated in TLR7 and autophagy activation. Interestingly, TLR7 activation attenuated UFA-induced lipid peroxidation products, such as malondialdehyde (MDA) and 4-Hydroxy-2-Nonenal (4-HNE). To clarify a possible pathway between TLR7 and lipid peroxidation, we treated hepatocytes with MDA and 4-HNE. MDA and 4-HNE induced 2-folds lipid accumulation in UFA-treated hepatocytes via blockade of the TLR7 signaling pathway’s IGF-1 release compared to only UFA-treated hepatocytes. In vivo experiments carried out with TLR7 knockout mice produced results consistent with in vitro experiments. In conclusion, TLR7 prevents progression of NAFLD via induced autophagy and released IGF-1 from liver. These findings suggest a new therapeutic strategy for the treatment of NAFLD. PMID:27279075

  2. Cell volume changes affect gluconeogenesis in the perfused liver of the catfish Clarias batrachus.

    PubMed

    Goswami, Carina; Datta, Shritapa; Biswas, Kuheli; Saha, Nirmalendu

    2004-09-01

    In addition to lactate and pyruvate, some amino acids were found to serve as potential gluconeogenic substrates in the perfused liver of Clarias batrachus. Glutamate was found to be the most effective substrate, followed by lactate, pyruvate, serine, ornithine, proline, glutamine, glycine, and aspartate. Four gluconeogenic enzymes, namely phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase (PC), fructose 1,6-bisphosphatase (FBPase) and glucose 6-phosphatase (G6Pase) could be detected mainly in liver and kidney, suggesting that the latter are the two major organs responsible for gluconeogenic activity in this fish. Hypo-osmotically induced cell swelling caused a significant decrease of gluconeogenic efflux accompanied with significant decrease of activities of PEPCK, FBPase and G6Pase enzymes in the perfused liver. Opposing effects were seen in response to hyperosmotically induced cell shrinkage. These changes were partly blocked in the presence of cycloheximide, suggesting that the aniso-osmotic regulations of gluconeogenesis possibly occurs through an inverse regulation of enzyme proteins and/or a regulatory protein synthesis in this catfish. In conclusion, gluconeogenesis appears to play a vital role in C. batrachus in maintaining glucose homeostasis, which is influenced by cell volume changes possibly for proper energy supply under osmotic stress.

  3. 2-Hydroxy-4-glutathion-S-yl-17beta-estradiol and 2-hydroxy-1-glutathion-S-yl-17beta-estradiol produce oxidative stress and renal toxicity in an animal model of 17beta-estradiol-mediated nephrocarcinogenicity.

    PubMed

    Butterworth, M; Lau, S S; Monks, T J

    1998-01-01

    Chronic exposure of male Syrian hamsters to a variety of estrogens has been linked with a high incidence of renal carcinoma. The basis of this species and tissue specificity remains to be resolved. We have recently shown that (i) 17beta-estradiol is nephrotoxic in the hamster in a manner dependent upon the activity of gamma-glutamyl transpeptidase and (ii) 17beta-estradiol is metabolized to a variety of catechol estrogen glutathione conjugates (Butterworth et al., Carcinogenesis, 18, 561-567, 1997). We report that the catechol estrogen glutathione conjugates exhibit redox properties similar to those of the catechol estrogens, and maintain the ability to generate superoxide radicals. Administration of 2-hydroxy-4-glutathion-S-yl-17beta-estradiol or 2-hydroxy-1-glutathion-S-yl-17beta-estradiol (0.27-5.0 micromol/kg) to Syrian hamsters, produces mild nephrotoxicity. Repeated daily administration of 2-hydroxy-4-glutathion-S-yl-17beta-estradiol causes a sustained elevation in urinary markers of renal damage and in the concentration of renal protein carbonyls and lipid hydroperoxides. Catechol estrogen oxidation and conjugation of glutathione in the liver, followed by the selective uptake of the redox active conjugates in tissues rich in gamma-glutamyl transpeptidase may contribute to 17beta-estradiol-induced renal tumors in the hamster.

  4. 77 FR 31722 - New Animal Drugs; Change of Sponsor; Estradiol; Estradiol Benzoate and Testosterone Propionate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-30

    ...). ENCORE (COMPUDOSE 400) 522.840 (estradiol benzoate). 135-906 COMPONENT E-H 522.842 (estradiol benzoate... COMPONENT E-C 522.1940 (progesterone and estradiol benzoate) with TYLAN (tylosin tartrate). COMPONENT E-S... estradiol) with TYLAN (tylosin tartrate). 200-224 COMPONENT T-H 522.2476 (trenbolone acetate) with TYLAN...

  5. Atrazine exposure affects growth, body condition and liver health in Xenopus laevis tadpoles.

    PubMed

    Zaya, Renee M; Amini, Zakariya; Whitaker, Ashley S; Kohler, Steven L; Ide, Charles F

    2011-08-01

    Six studies were performed regarding the effects of atrazine, the most frequently detected pesticide in fresh water in the US, on developing Xenopus laevis tadpoles exposed 5 days post-hatch through Nieuwkoop Faber Stage 62. The levels of atrazine tested included those potentially found in puddles, vernal ponds and runoff soon after application (200 and 400 μg/L) and a low level studied by a number of other investigators (25 μg/L). One study tested 0, 25 and 200 μg/L, another tested 0, 200 and 400 μg/L, while the remaining four studies tested 0 and 400 μg/L. During all exposures, mortality, growth, metamorphosis, sex ratio, fat body (a lipid storage organ) size and liver weights, both relative to body weight, were evaluated. In selected studies, feeding behavior was recorded, livers and fat bodies were histologically evaluated, liver glycogen and lipid content were determined by image analysis, and immunohistochemical detection of activated caspase-3 in hepatocytes was performed. The NOEC was 25 μg/L. None of these exposure levels changed sex ratios nor were intersex gonads noted, however, no definitive histological evaluation of the gonads was performed. Although a marginal increase in mortality at the 200 μg/L level was noted, this was not statistically significant. Nor was there an increase in mortality at 400 μg/L versus controls. At the 400 μg/L level, tadpoles were smaller than controls by 72 h of exposure and remained smaller throughout the entire exposure. Appetite was not decreased at any exposure level. Slowed metamorphosis was noted only at 400 μg/L in two of five studies. Livers were significantly smaller in the study that tested both 200 and 400 μg/L, yet no pathological changes or differences in glycogen or lipid stores were noted. However, livers from 400 μg/L exposed tadpoles had higher numbers of activated caspase-3 immunopositive cells suggesting increased rates of apoptosis. Fat body size decreased significantly after exposure to 200

  6. Arginine supplementation and exposure time affects polyamine and glucose metabolism in primary liver cells isolated from Atlantic salmon.

    PubMed

    Andersen, Synne Marte; Taylor, Richard; Holen, Elisabeth; Aksnes, Anders; Espe, Marit

    2014-05-01

    Arginine has been demonstrated to enhance glucose and lipid oxidation in mammals through activation of polyamine turnover. We aimed to investigate how arginine affects energy utilization through polyamine metabolism and whether this effect is time dependent. Primary liver cells were isolated from Atlantic salmon (2.2 kg body weight) fed diets containing 25.5 (low arginine, LA) or 36.1 (high arginine, HA) g arginine/kg dry matter for 12 weeks, to investigate the effect of long-term arginine supplementation. The cells were cultured for 24 h in L-15 medium to which either alpha-difluoromethylornithine (DFMO) or N (1),N (11)-diethylnorspermine (DENSPM) was added. Analysis of the medium by nuclear magnetic resonance revealed significant differences between the two dietary groups as well as between cells exposed to DFMO and DENSPM, with decreased glucose, fumarate and lactate concentrations in media of the HA cells. Liver cells from fish fed the HA diet had higher spermidine/spermine-N1-acetyltransferase protein abundance and lower adenosine triphosphate concentration as compared to the LA-fed fish, while gene expression was not affected by either diet or treatment. Primary liver cells isolated from salmon fed a commercial diet and cultured in L-15 media with or without arginine supplementation (1.82 or 3.63 mM) for 48 h, representing short-term effect of arginine supplementation, showed differential expression of genes for apoptosis and polyamine synthesis due to arginine supplementation or inhibition by DFMO. Overall, arginine concentration and exposure time affected energy metabolism and gene regulation more than inhibition or activation of key enzymes of polyamine metabolism, suggesting a polyamine-independent influence of arginine on cellular energy metabolism and survival.

  7. Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review

    PubMed Central

    Severson, Tyler J; Besur, Siddesh; Bonkovsky, Herbert L

    2016-01-01

    AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review. METHODS: The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur. RESULTS: We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFNλ4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine. CONCLUSION: Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management. PMID:27547017

  8. Energy restriction affect liver development in Hu sheep ram lambs through Hippo signaling pathway.

    PubMed

    Zhang, Ting-Ting; Zhang, Guo-Min; Jin, Yu-Hang; Guo, Yi-Xuan; Wang, Zhen; Fan, Yi-Xuan; El-Samahy, M A; Wang, Feng

    2017-09-02

    This study aimed to evaluate the effects of dietary energy restriction on postnatal liver development in Hu sheep ram lambs. A total of 16 ram lambs were randomly divided into two groups: 100% energy requirements diet and 55% energy requirements diet, which were fed for 75 d. Results showed that the final body and liver weights decreased with energy restriction (p <0.05). Energy restriction caused a significant decrease in the levels of circulating insulin-like growth factor 1 (IGF1) and an increase in growth hormone secretion (p <0.05), which can be explained by the decreased mRNA expression levels of the growth hormone receptor (GHR) and IGF1 (p <0.05). The proliferating cell nuclear antigen (PCNA), Ki-67 and apoptosis-related proteins (BAX and BCL2) were mainly located in the nucleus and the cytoplasm of hepatocytes, respectively. The transcription and protein levels of PCNA and BAX were significantly decreased and increased by energy restriction, respectively (p <0.05). The caspase9 and caspase3 mRNA and activity were increased in energy restriction group (p <0.05). Moreover, Hippo signaling pathway proteins [mammalian sterile 20-like protein kinase 1 (MST1), large tumor suppressor kinase 1 (LATS1), and yes-associated protein 1 (YAP1)] were mainly observed around the hepatic portal area, and the expression levels of their mRNA and proteins were significantly decreased in energy restriction group (p <0.05). In summary, energy restriction in ram lambs impairs liver development by increasing apoptosis, which may occur via the Hippo signaling pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Dietary conjugated linoleic acid affects blood parameters, liver morphology and expression of selected hepatic genes in laying hens.

    PubMed

    Koronowicz, A A; Banks, P; Szymczyk, B; Leszczyńska, T; Master, A; Piasna, E; Szczepański, W; Domagała, D; Kopeć, A; Piątkowska, E; Laidler, P

    2016-10-01

    The objective of this research were to investigate the effect of a conjugated linoleic acid (CLA)-enriched diet on Isa Brown laying hen health status and to provide a comprehensive analysis of changes in blood parameters, liver morphology and selected hepatic gene expression. Hens were allocated to the control and experimental group (diet enriched with 0.75% CLA) for a total period of 4 m. At the end of the experiment half of the hens from each group were slaughtered for analyses. The remaining hens were transferred to an organic farm for the next 5 m and fed on the diet without CLA supplementation. The CLA-enriched diet resulted in significant changes in blood and serum parameters; specifically, haematocrit (HCT), mean corpuscular volume (MCV) and white blood cells (WBC) count were decreased compared to the control. The total cholesterol (TC) was not significantly affected while the triacylglycerol's (TG) concentration was elevated. The activity of alanine aminotransferase (ALT) was significantly increased in the CLA-supplemented group, while aspartate aminotransferase (AST) showed an increasing tendency. Liver biopsies showed pathological changes classified as non-alcoholic fatty liver disease (NAFLD). Additionally, the expression of hepatic genes involved in fatty acids synthesis (ME1, ACLY, ACC, FASN, SCD1), oxidation (CPT1α, PPARA), detoxification processes (Cytochrome P450, CYP, Flavin-containing monooxygenase, FMO3), oxidative stress (NOX4, XbP1) and inflammation (IL6, TNFα) were elevated. Cessation of CLA supplementation for 5 m of organic farming resulted in normalisation of blood and hepatic parameters to the levels observed in control hens. The results of this study indicate that dietary CLA triggers an integrated stress response in laying hens and activates mechanisms involved in liver detoxification.

  10. [Metabolism of lipoproteins in rats treated with ethinyl estradiol].

    PubMed

    Tvorogova, M G; Titov, V N

    1986-01-01

    Effect of ethinyl-estradiol on metabolism of lipoproteins was studied in rat blood. Administration of ethinyl-estradiol at a dose of 50 micrograms/kg of body mass led to hypocholesterolemia and to hypertriglyceridemia in blood of experimental animals as well as the hormone impaired lipid composition of all the lipoprotein classes. These alterations in lipid composition of lipoproteins occurred as a result of an increase in biosynthesis and secretion of very low density lipoproteins as well as due to impairments of lipoprotein transformation in blood serum caused by a decrease in activity of main enzymes responsible for the transformation of lipoproteins in circulation--lipoprotein lipase, liver triglyceride lipase and lecithin-cholesterol acyltransferase.

  11. Perchlorate exposure induces hypothyroidism and affects thyroid-responsive genes in liver but not brain of quail chicks.

    PubMed

    Chen, Yu; McNabb, F M Anne; Sible, Jill C

    2009-10-01

    Ground-dwelling birds in perchlorate-contaminated areas are exposed to perchlorate ion, a known thyroid disruptor, and might be vulnerable to the developmental effects of perchlorate-induced hypothyroidism. We hypothesized that perchlorate-induced hypothyroidism would alter the expression of thyroid-responsive genes involved in thyroid hormone (TH) regulation and in the development of target organ function. Japanese quail chicks were exposed to 2000 mg/L ammonium perchlorate in drinking water for 7.5 weeks beginning on day 5 posthatch. Hypothyroidism was evident after 2 weeks of exposure as lower plasma THs and lower TH content in exposed chicks than in controls. The degree of hypothyroidism was increased at 7.5 weeks, as indicated by significant thyroid gland hypertrophy and sustained changes in thyroid function. After 2 weeks of exposure, hypothyroidism increased type 2 5'-deiodinase (D2) mRNA level and decreased Spot 14 (SP14) mRNA level in the liver, whereas D2 mRNA and RC3 mRNA levels in brain were not affected. After 7.5 weeks of exposure, mRNA levels in the exposed group did not differ from those in controls in either the liver or brain, suggesting the responsiveness of these genes to THs decreased during development. These results suggest that the brain, but not the liver, was protected from the effects of hypothyroidism, probably by changes in D2 activity at the protein level and/or regulation of TH entry and exit from the brain. We concluded that perchlorate exposure caused hypothyroidism in young Japanese quail and affected the expression of thyroid-responsive genes during early posthatch development.

  12. Dietary fatty acids affect mitochondrial phospholipid compositions and mitochondrial gene expression of rainbow trout liver at different ages.

    PubMed

    Almaida-Pagán, P F; De Santis, C; Rubio-Mejía, O L; Tocher, D R

    2015-01-01

    Mitochondria are among the first responders to various stressors that challenge the homeostasis of cells and organisms. Mitochondrial decay is generally associated with impairment in the organelle bioenergetics function and increased oxidative stress, and it appears that deterioration of mitochondrial inner membrane phospholipids (PL), particularly cardiolipin (CL), and accumulation of mitochondrial DNA (mtDNA) mutations are among the main mechanisms involved in this process. In the present study, liver mitochondrial membrane PL compositions, lipid peroxidation, and mtDNA gene expression were analyzed in rainbow trout fed three diets with the same base formulation but with lipid supplied either by fish oil (FO), rapeseed oil (RO), or high DHA oil (DHA) during 6 weeks. Specifically, two feeding trials were performed using fish from the same population of two ages (1 and 3 years), and PL class compositions of liver mitochondria, fatty acid composition of individual PL classes, TBARS content, and mtDNA expression were determined. Dietary fatty acid composition strongly affected mitochondrial membrane composition from trout liver but observed changes did not fully reflect the diet, particularly when it contained high DHA. The changes were PL specific, CL being particularly resistant to changes in DHA. Some significant differences observed in expression of mtDNA with diet may suggest long-term dietary effects in mitochondrial gene expression which could affect electron transport chain function. All the changes were influenced by fish age, which could be related to the different growth rates observed between 1- and 3-year-old trout but that could also indicate age-related changes in the ability to maintain structural homeostasis of mitochondrial membranes.

  13. Effects of 17α-ethinyl estradiol exposure on estrogen receptors α and β and vitellogenins A, B and C mRNA expression in the liver of sand goby (Pomatoschistus minutus).

    PubMed

    Humble, Joseph L; Saaristo, Minna; Lindström, Kai; Lehtonen, Kari K; Craft, John A

    2014-05-01

    This study aims to characterize the estrogen receptor (er) in sand goby (Pomatoschistus minutus) and determine the temporal effects of 17α-ethinyl estradiol (EE2) on erα and vitellogenin (vtg) gene expression in males. Two partial cDNA sequences (erα and erβ1) are presented showing conserved structural features with ers of other species. Transcript levels for both ers were low in control fish but EE2 exposure (11 ng/L, for 29 days) increased both to a pattern similar to vitellogenic females. The relative expression of three vtg genes (vtga, vtgb and vtgc) along with erα was determined in control and male fish exposed to EE2 (11 ng/L) at multiple time-points over 29 days. All four transcripts were significantly induced due to exposure and expression rose during the time course with distinct temporal patterns and vtga reached a substantially higher level at the end of the time course coinciding with rapid elevation in erα expression.

  14. Steroid beta-D-glucosidase in steer liver and kidney.

    PubMed

    Williamson, D G; Gwilliam, C; Layne, D S

    1977-01-01

    Homogenates of liver and kidney tissue from young steers had beta-D-glucosidase (EC 3.2.1.21) activity toward 17alpha-estradiol-3-glucoside, 17beta-estradiol-3-glucoside, 17alpha-estradiol-17-glucoside, and deoxycorticosterone-21-glucoside. The activity towards the phenolic 3-glucosides was largely present in the 100 000 X g supernatant, while that towards 17alpha-estradiol-17-glucoside was concentrated in the microsomes. The use of beef liver preparations for the hydrolysis of steroid 'glucuronide' fractions could result in hydrolysis of other steroid glycosides which might be present.

  15. Circadian-clock system in mouse liver affected by insulin resistance.

    PubMed

    Yang, Shu-Chuan; Tseng, Huey-Lin; Shieh, Kun-Ruey

    2013-07-01

    Circadian rhythms are exhibited in the physiological and behavioral processes of all mammals; they are generated by intracellular levels of circadian oscillators, which are named as a set of circadian-clock genes. These genes compose the transcriptional/translational feedback loops to regulate not only circadian rhythmicity, but also energy metabolism. Previous studies have shown that obesity and diabetes cause the dysregulation of the circadian-clock system, and vice versa. However, some diabetes subjects are lean with insulin resistance and the mechanisms of insulin resistance without obesity are much less well known. Therefore, whether insulin resistance alone is enough to influence the expression of circadian-clock genes is uncertain. This study employs a neonatal streptozotocin (STZ)-treated paradigm in mice to model the molecular and physiological progress of nonobese insulin resistance. A single injection of STZ into 2-d-old male C57BL/6 mice induces nonobese, hyperglycemic and hyperinsulinemic conditions, and the levels of gene expression in the liver by a real-time quantitative polymerase chain reaction are then measured. Although the levels of Bmal1 (brain and muscle Arnt-like protein-1), Per2 (period 2), and Cry1 (cryptochrome 1) mRNA expression in the liver change during the progress of insulin resistance conditions, the gene expression patterns still show circadian rhythmicity. This study suggests that changes in the hepatic circadian-clock gene expression mark an early event in the metabolic disruption associated with insulin resistance. Furthermore, 2 wks of treatment with the thiazolidinedione, pioglitazone, fully resolve the dysfunction in metabolic parameters and the changes in circadian-clock gene expression from early insulin resistance conditions. These results indicate that the circadian-clock system is sensitive to insulin resistance, and that treatment with thiazolidinediones can resolve changes in the circadian-clock system in a timely

  16. Estradiol Membrane-Initiated Signaling and Female Reproduction.

    PubMed

    Micevych, Paul E; Wong, Angela May; Mittelman-Smith, Melinda Anne

    2015-07-01

    The discoveries of rapid, membrane-initiated steroid actions and central nervous system steroidogenesis have changed our understanding of the neuroendocrinology of reproduction. Classical nuclear actions of estradiol and progesterone steroids affecting transcription are essential. However, with the discoveries of membrane-associated steroid receptors, it is becoming clear that estradiol and progesterone have neurotransmitter-like actions activating intracellular events. Ultimately, membrane-initiated actions can influence transcription. Estradiol membrane-initiated signaling (EMS) modulates female sexual receptivity and estrogen feedback regulating the luteinizing hormone (LH) surge. In the arcuate nucleus, EMS activates a lordosis-regulating circuit that extends to the medial preoptic nucleus and subsequently to the ventromedial nucleus (VMH)--the output from the limbic and hypothalamic regions. Here, we discuss how EMS leads to an active inhibition of lordosis behavior. To stimulate ovulation, EMS facilitates astrocyte synthesis of progesterone (neuroP) in the hypothalamus. Regulation of GnRH release driving the LH surge is dependent on estradiol-sensitive kisspeptin (Kiss1) expression in the rostral periventricular nucleus of the third ventricle (RP3V). NeuroP activation of the LH surge depends on Kiss1, but the specifics of signaling have not been well elucidated. RP3V Kiss1 neurons appear to integrate estradiol and progesterone information which feeds back onto GnRH neurons to stimulate the LH surge. In a second population of Kiss1 neurons, estradiol suppresses the surge but maintains tonic LH release, another critical component of the estrous cycle. Together, evidence suggests that regulation of reproduction involves membrane action of steroids, some of which are synthesized in the brain.

  17. Estradiol Membrane-Initiated Signaling and Female Reproduction

    PubMed Central

    Micevych, Paul E; Wong, Angela May; Mittelman-Smith, Melinda Anne

    2016-01-01

    The discoveries of rapid, membrane-initiated steroid actions and central nervous system steroidogenesis have changed our understanding of the neuroendocrinology of reproduction. Classical nuclear actions of estradiol and progesterone steroids affecting transcription are essential. However, with the discoveries of membrane-associated steroid receptors, it is becoming clear that estradiol and progesterone have neurotransmitter-like actions activating intracellular events. Ultimately, membrane-initiated actions can influence transcription. Estradiol membrane-initiated signaling (EMS) modulates female sexual receptivity and estrogen feedback regulating the luteinizing hormone (LH) surge. In the arcuate nucleus, EMS activates a lordosis-regulating circuit that extends to the medial preoptic nucleus and subsequently to the ventromedial nucleus (VMH)—the output from the limbic and hypothalamic regions. Here, we discuss how EMS leads to an active inhibition of lordosis behavior. To stimulate ovulation, EMS facilitates astrocyte synthesis of progesterone (neuroP) in the hypothalamus. Regulation of GnRH release driving the LH surge is dependent on estradiol-sensitive kisspeptin (Kiss1) expression in the rostral periventricular nucleus of the third ventricle (RP3V). NeuroP activation of the LH surge depends on Kiss1, but the specifics of signaling have not been well elucidated. RP3V Kiss1 neurons appear to integrate estradiol and progesterone information which feeds back onto GnRH neurons to stimulate the LH surge. In a second population of Kiss1 neurons, estradiol suppresses the surge but maintains tonic LH release, another critical component of the estrous cycle. Together, evidence suggests that regulation of reproduction involves membrane action of steroids, some of which are synthesized in the brain. PMID:26140715

  18. Catechol-O-methyltransferase is dispensable for vascular protection by estradiol in mouse models of atherosclerosis and neointima formation.

    PubMed

    Wilhelmson, Anna S; Bourghardt-Fagman, Johan; Gogos, Joseph A; Fogelstrand, Per; Tivesten, Asa

    2011-12-01

    Estradiol is converted to the biologically active metabolite 2-methoxyestradiol via the activity of the enzyme catechol-O-methyltransferase (COMT). Exogenous administration of both estradiol and 2-methoxyestradiol reduces experimental atherosclerosis and neointima formation, and COMT-dependent formation of 2-methoxyestradiol likely mediates the antimitogenic effect of estradiol on smooth muscle cells in vitro. This study evaluated whether 2-methoxyestradiol mediates the vasculoprotective actions of estradiol in vivo. Wild-type (WT) and COMT knockout (COMTKO) mice on an apolipoprotein E-deficient background were gonadectomized and treated with estradiol or placebo. Exogenous estradiol reduced atherosclerotic lesion formation in both females (WT, -78%; COMTKO, -82%) and males (WT, -48%; COMTKO, -53%) and was equally effective in both genotypes. We further evaluated how exogenous estradiol affected neointima formation after ligation of the carotid artery in ovariectomized female mice; estradiol reduced intimal hyperplasia to a similar extent in both WT (-80%) and COMTKO (-77%) mice. In ovarian-intact female COMTKO mice, atherosclerosis was decreased (-25%) compared with WT controls. In conclusion, the COMT enzyme is dispensable for vascular protection by exogenous estradiol in experimental atherosclerosis and neointima formation in vivo. Instead, COMT deficiency in virgin female mice with intact endogenous production of estradiol results in relative protection against atherosclerosis.

  19. 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...

  20. 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...

  1. A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties.

    PubMed

    Clark, A M; Wheeler, S E; Young, C L; Stockdale, L; Shepard Neiman, J; Zhao, W; Stolz, D B; Venkataramanan, R; Lauffenburger, D; Griffith, L; Wells, A

    2016-12-20

    Distant metastasis is the major cause of breast cancer-related mortality, commonly emerging clinically after 5 or more years of seeming 'cure' of the primary tumor, indicating a quiescent dormancy. The lack of relevant accessible model systems for metastasis that recreate this latent stage has hindered our understanding of the molecular basis and the development of therapies against these lethal outgrowths. We previously reported on the development of an all-human 3D ex vivo hepatic microphysiological system that reproduces several features of liver physiology and enables spontaneous dormancy in a subpopulation of breast cancer cells. However, we observed that the dormant cells were localized primarily within the 3D tissue, while the proliferative cells were in contact with the polystyrene scaffold. As matrix stiffness is known to drive inflammatory and malignant behaviors, we explored the occurrence of spontaneous tumor dormancy and inflammatory phenotype. The microphysiological system was retrofitted with PEGDa-SynKRGD hydrogel scaffolding, which is softer and differs in the interface with the tissue. The microphysiological system incorporated donor-matched primary human hepatocytes and non-parenchymal cells (NPCs), with MDA-MB-231 breast cancer cells. Hepatic tissue in hydrogel scaffolds secreted lower levels of pro-inflammatory analytes, and was more responsive to inflammatory stimuli. The proportion of tumor cells entering dormancy was markedly increased in the hydrogel-supported tissue compared to polystyrene. Interestingly, an unexpected differential response of dormant cells to varying chemotherapeutic doses was identified, which if reflective of patient pathophysiology, has important implications for patient dosing regimens. These findings highlight the metastatic microphysiological system fitted with hydrogel scaffolds as a critical tool in the assessment and development of therapeutic strategies to target dormant metastatic breast cancer.

  2. Estradiol regulates human QT-interval: acceleration of cardiac repolarization by enhanced KCNH2 membrane trafficking.

    PubMed

    Anneken, Lars; Baumann, Stefan; Vigneault, Patrick; Biliczki, Peter; Friedrich, Corinna; Xiao, Ling; Girmatsion, Zenawit; Takac, Ina; Brandes, Ralf P; Kissler, Stefan; Wiegratz, Inka; Zumhagen, Sven; Stallmeyer, Birgit; Hohnloser, Stefan H; Klingenheben, Thomas; Schulze-Bahr, Eric; Nattel, Stanley; Ehrlich, Joachim R

    2016-02-14

    Modulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms. We measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy. Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles. A comprehensive cellular and molecular analysis was done to identify the mechanisms of hormonal QT-interval regulation. High estradiol levels, but neither progesterone nor estradiol/progesterone ratio, inversely correlated with QTc. Consistent with clinical data, in vitro estradiol stimulation (60 pmol/L, 48 h) enhanced IKCNH2. This increase was mediated by estradiol receptor-α-dependent promotion of KCNH2-channel trafficking to the cell membrane. To study the underlying mechanism, we focused on heat-shock proteins. The heat-shock protein-90 (Hsp90) inhibitor geldanamycin abolished estradiol-induced increase in IKCNH2. Geldanamycin had no effect on KCNH2 transcription or translation; nor did it affect expression of estradiol receptors and chaperones. Estradiol enhanced the physical interaction of KCNH2-channel subunits with heat-shock proteins and augmented ion-channel trafficking to the membrane. Elevated estradiol levels were associated with shorter QTc intervals in healthy women and female LQT-2 patients. Estradiol acts on KCNH2 channels via enhanced estradiol-receptor-α-mediated Hsp90 interaction, augments membrane trafficking and thereby increases repolarizing current. These results provide mechanistic insights into hormonal control of human ventricular repolarization and open novel therapeutic avenues. Published on behalf of the European Society of Cardiology. All rights

  3. Estradiol regulates human QT-interval: acceleration of cardiac repolarization by enhanced KCNH2 membrane trafficking

    PubMed Central

    Anneken, Lars; Baumann, Stefan; Vigneault, Patrick; Biliczki, Peter; Friedrich, Corinna; Xiao, Ling; Girmatsion, Zenawit; Takac, Ina; Brandes, Ralf P.; Kissler, Stefan; Wiegratz, Inka; Zumhagen, Sven; Stallmeyer, Birgit; Hohnloser, Stefan H.; Klingenheben, Thomas; Schulze-Bahr, Eric; Nattel, Stanley; Ehrlich, Joachim R.

    2016-01-01

    Background Modulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms. Methods and results We measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy. Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles. A comprehensive cellular and molecular analysis was done to identify the mechanisms of hormonal QT-interval regulation. High estradiol levels, but neither progesterone nor estradiol/progesterone ratio, inversely correlated with QTc. Consistent with clinical data, in vitro estradiol stimulation (60 pmol/L, 48 h) enhanced IKCNH2. This increase was mediated by estradiol receptor-α-dependent promotion of KCNH2-channel trafficking to the cell membrane. To study the underlying mechanism, we focused on heat-shock proteins. The heat-shock protein-90 (Hsp90) inhibitor geldanamycin abolished estradiol-induced increase in IKCNH2. Geldanamycin had no effect on KCNH2 transcription or translation; nor did it affect expression of estradiol receptors and chaperones. Estradiol enhanced the physical interaction of KCNH2-channel subunits with heat-shock proteins and augmented ion-channel trafficking to the membrane. Conclusion Elevated estradiol levels were associated with shorter QTc intervals in healthy women and female LQT-2 patients. Estradiol acts on KCNH2 channels via enhanced estradiol-receptor-α-mediated Hsp90 interaction, augments membrane trafficking and thereby increases repolarizing current. These results provide mechanistic insights into hormonal control of human ventricular repolarization and open novel therapeutic avenues. PMID:26271031

  4. [Oral combined contraception: is there any difference between ethinyl-estradiol and estradiol?].

    PubMed

    Trémollieres, F

    2012-02-01

    Estradiol 17-β, which is the natural estrogen in women, offers an alternative to ethinyl-estradiol to be used in combined oral contraceptives. Thanks to its biochemical structure, estradiol has a far lesser impact on the synthesis of hepatic proteins than ethinyl-estradiol, which is likely to result in a better metabolic and vascular profile. However and until lately, the different clinical trials that had investigated estradiol-containing oral contraceptives were limited by bleeding disturbances, with breakthrough and irregular bleeding and higher rates of discontinuation. Development of anti-gonadotropic progestins with a potent endometrial activity is likely to make possible their combination with estradiol in oral contraceptives. The objective of this current review is to provide an overview of the development of combined oral contraceptives containing natural estrogen from the respective biochemical and pharmacological characteristics of ethinyl-estradiol and estradiol.

  5. Absorption and distribution of estradiol from male seminal emissions during mating

    PubMed Central

    Pollock, Tyler

    2016-01-01

    Estradiol-17β (E2) plays critical roles in female maturation, sexual receptivity, ovulation and fertility. In many mammals, contact with males can similarly affect these female parameters, whereas male excretions contain significant quantities of E2. We administered radiolabeled estradiol ([3H]E2) to male mice in doses representing a small fraction of their endogenous E2. These males were paired with sexually receptive females, and radioactivity was traced into the females’ systems. In Experiment 1, males were given [3H]E2 at 24 and 1 h before mating. Male-to-female [3H]E2 transfer intensified with increasing numbers of intromissions and spiked in the uterus after insemination. In Experiment 2, sexually experienced young males received [3H]E2 at 72 and 24 h before mating, and all mated to ejaculation. The copulatory plug deposited in the female reproductive tract contained substantial levels of radioactivity. The uteri, other tissues and blood serum of females displayed radioactivity indicative of E2 transfer. In Experiment 3, radioactivity was observed 3 and 18 h after insemination in the females’ uteri and other tissues, including parts of the brain. In Experiment 4, we observed substantial levels of radioactivity in semen as well as the copulatory plugs retrieved from the females after mating. Transferred E2 could directly affect abundant estrogen receptors in the female reproductive tract without potential metabolism by the liver. Sexually transferred E2 may facilitate uterine preparation for blastocyst implantation. These data converge with several lines of evidence indicating that male-sourced E2 can transfer to proximate females in bioactive form, contributing to various mammalian pheromonal effects. PMID:27758953

  6. Parameters affecting different acoustic radiation force impulse applications in the diagnosis of fibrotic liver changes

    PubMed Central

    Galgenmueller, Sabrina; Jaeger, Heike; Kratzer, Wolfgang; Schmidt, Stefan A; Oeztuerk, Suemeyra; Haenle, Mark M; Mason, Richard A; Graeter, Tilmann

    2015-01-01

    AIM: To analyze the virtual touch tissue quantification (VTTQ) and virtual touch imaging quantification (VTIQ) techniques, and identify possible factors that may influence VTTQ and VTIQ measurements. METHODS: One hundred and eighty-six (104 women/82 men) of 323 subjects met the inclusion criteria (age > 18 years, no history of chronic or gastrointestinal disease, body-mass index (BMI) < 30 kg/m², a fasting period of at least three hours, no history of hepatotoxic pharmaceuticals, alcohol consumption < 24 g/d in men and < 12 g/d in women, and normal findings upon ultrasound examination of the abdomen). Measurements were taken at depths of 50 mm with VTTQ, 15 mm and 25 mm with VTIQ in the right hepatic lobe, and at 15 mm with only VTIQ in the left hepatic lobe. The examiner acquired six measurements per position, thereby giving 24 measurements in total. RESULTS: The 95% confidence intervals of mean were 1.23-1.29 m/s for VTTQ and 1.29-1.37 m/s, 1.17-1.23 m/s, and 1.48-1.57 m/s for VTIQ in a depth of 15 mm and 25 mm in the right hepatic lobe and 15 mm in the left hepatic lobe. Only superficial measurements in the right hepatic lobe with the VTIQ method exhibited an effect of age on shear wave velocity. Measurements acquired using the 6C1 probe with the VTTQ method showed no dependence on BMI. By comparison, BMI influenced measurements taken with the VTIQ method using the 9L4 probe in the superficial and deep areas of the right hepatic lobe, as well as in the left hepatic lobe (P = 0.0160, P = 0.0019, P = 0.0173, respectively). Gender influenced measurements at depths of 50 mm with VTTQ and 25 mm with VTIQ in the right hepatic lobe (P = 0.0001, P = 0.0269). Significant differences were found between measurements with the 6C1 (VTTQ) and 9L4 probes (VTIQ) (P = 0.0067), between superficial and deep measurements (P < 0.0001), and between the right and left lobes of the liver (P < 0.0001). CONCLUSION: Measurements in the right lobe and deep regions are preferable. Gender

  7. Xenobiotic-contaminated diets affect hepatic lipid metabolism: Implications for liver steatosis in Sparus aurata juveniles.

    PubMed

    Maradonna, F; Nozzi, V; Santangeli, S; Traversi, I; Gallo, P; Fattore, E; Mita, D G; Mandich, A; Carnevali, O

    2015-10-01

    The metabolic effects induced by feed contaminated with a lower or a higher concentration of -nonylpnenol (NP), 4-tert-octylphenol (t-OP) or bisphenol A (BPA), three environmental endocrine disruptors, were assessed in juvenile sea bream liver. Histological analysis demonstrated that all these three xenobiotics induced hepatic lipid accumulation and steatosis. These findings prompted analysis of the expression of the major molecules involved in lipid metabolism: peroxisome proliferator activated receptors (which is encoded by ppars), fatty acid synthase (encoded by fas), lipoprotein lipase (encoded by lpl) and hormone-sensitive lipase (encoded by hsl). The enzymes encoded by ppars and fas are in fact responsible for lipid accumulation, whereas lpl- and hsl- encoded proteins play a pivotal role in fat mobilization. The three xenobiotics modulated ppar mRNA expression: pparα mRNA expression was induced by the higher dose of each contaminant; pparβ mRNA expression was upregulated by the lower doses and in BPA2 fish ppary mRNA overexpression was induced by all pollutants. These data agreed with the lipid accumulation profiles documented by histology. Fas mRNA levels were modulated by the two NP doses and the higher BPA concentration. Lpl mRNA was significantly upregulated in all experimental groups except for BPA1 fish while hsl mRNA was significantly downregulated in all groups except for t-OP2 and BPA1 fish. The plasma concentrations of cortisol, the primary stress biomarker, were correlated with the levels of pepck mRNA level. This gene encodes phosphoenolpyruvate carboxykinase which is one of the key enzymes of gluconeogenesis. Pepck mRNA was significantly overexpressed in fish exposed to NP2 and both t-OP doses. Finally, the genes encoding cyclooxygenase 2 (cox2) and 5-lipoxygenase (5 lox), the products of which are involved in the inflammatory response, transcriptions were significantly upregulated in NP and BPA fish, whereas they were unchanged in t

  8. Mechanism of estradiol-induced block of voltage-gated K+ currents in rat medial preoptic neurons.

    PubMed

    Druzin, Michael; Malinina, Evgenya; Grimsholm, Ola; Johansson, Staffan

    2011-01-01

    The present study was conducted to characterize possible rapid effects of 17-β-estradiol on voltage-gated K(+) channels in preoptic neurons and, in particular, to identify the mechanisms by which 17-β-estradiol affects the K(+) channels. Whole-cell currents from dissociated rat preoptic neurons were studied by perforated-patch recording. 17-β-Estradiol rapidly (within seconds) and reversibly reduced the K(+) currents, showing an EC(50) value of 9.7 µM. The effect was slightly voltage dependent, but independent of external Ca(2+), and not sensitive to an estrogen-receptor blocker. Although 17-α-estradiol also significantly reduced the K(+) currents, membrane-impermeant forms of estradiol did not reduce the K(+) currents and other estrogens, testosterone and cholesterol were considerably less effective. The reduction induced by estradiol was overlapping with that of the K(V)-2-channel blocker r-stromatoxin-1. The time course of K(+) current in 17-β-estradiol, with a time-dependent inhibition and a slight dependence on external K(+), suggested an open-channel block mechanism. The properties of block were predicted from a computational model where 17-β-estradiol binds to open K(+) channels. It was concluded that 17-β-estradiol rapidly reduces voltage-gated K(+) currents in a way consistent with an open-channel block mechanism. This suggests a new mechanism for steroid action on ion channels.

  9. Mechanism of Estradiol-Induced Block of Voltage-Gated K+ Currents in Rat Medial Preoptic Neurons

    PubMed Central

    Druzin, Michael; Malinina, Evgenya; Grimsholm, Ola; Johansson, Staffan

    2011-01-01

    The present study was conducted to characterize possible rapid effects of 17-β-estradiol on voltage-gated K+ channels in preoptic neurons and, in particular, to identify the mechanisms by which 17-β-estradiol affects the K+ channels. Whole-cell currents from dissociated rat preoptic neurons were studied by perforated-patch recording. 17-β-estradiol rapidly (within seconds) and reversibly reduced the K+ currents, showing an EC50 value of 9.7 µM. The effect was slightly voltage dependent, but independent of external Ca2+, and not sensitive to an estrogen-receptor blocker. Although 17-α-estradiol also significantly reduced the K+ currents, membrane-impermeant forms of estradiol did not reduce the K+ currents and other estrogens, testosterone and cholesterol were considerably less effective. The reduction induced by estradiol was overlapping with that of the KV-2-channel blocker r-stromatoxin-1. The time course of K+ current in 17-β-estradiol, with a time-dependent inhibition and a slight dependence on external K+, suggested an open-channel block mechanism. The properties of block were predicted from a computational model where 17-β-estradiol binds to open K+ channels. It was concluded that 17-β-estradiol rapidly reduces voltage-gated K+ currents in a way consistent with an open-channel block mechanism. This suggests a new mechanism for steroid action on ion channels. PMID:21625454

  10. Catalase and estradiol inhibit mitochondrial protein S-glutathionylation.

    PubMed

    Hu, Bin; Allina, Jorge; Bai, Jingxiang; Kesar, Vivek; Odin, Joseph A

    2012-08-01

    Regulation and downstream effects of mitochondrial protein S-glutathionylation in response to oxidative stress are poorly understood. The study aim was to determine whether anti-oxidants such as catalase and estradiol alter mitochondrial protein S-glutathionylation and in turn affect apoptosis following ultraviolet B (UV-B) light irradiation. HeLa cells were transduced with increasing amounts of adenovirus encoding catalase (Ad-Cat) and β-galactosidase (Ad-Lac Z) or pre-incubated with estradiol before induction of apoptosis by UV-B light exposure. Inhibition of mitochondrial protein S-glutathionylation was assessed using autoantibodies specific for the non-S-glutathionylated form of PDC-E2. The percentage of apoptotic cells following UV-B irradiation were not significantly different between mock cells (cells with no virus infection) and Ad-Cat and Ad-Lac Z infected cells at all viral doses (all p > 0.050). Autoantibody staining of non-S-glutathionylated PDC-E2 in apoptotic cells was three times greater in only Ad-Cat infected cells compared to only Ad-Lac Z infected cells (81.3 ± 16.7 vs 26 ± 7.2 %, respectively, p = 0.030). Similarly estradiol treatment (33 and 100 nM) also significantly increased PDC-E2 staining in apoptotic cells compared to non-treated cells (both p < 0.010). The percentage of apoptotic cells was not significantly different with any of the estradiol concentrations (all p > 0.100). The observed procaspase 12 cleavage following UV-B irradiation suggests that a mitochondrial-independent apoptotic pathway was activated. In conclusion, following an apoptotic stimulus, estradiol may inhibit mitochondrial protein S-glutathionylation without inhibiting apoptosis. This effect may play a role in ninefold greater prevalence of autoantibodies against PDC-E2 in women with primary biliary cirrhosis.

  11. 21 CFR 522.840 - Estradiol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Estradiol. 522.840 Section 522.840 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 DRUGS § 522.840 Estradiol....

  12. 21 CFR 522.840 - Estradiol.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Estradiol. 522.840 Section 522.840 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 DRUGS § 522.840 Estradiol....

  13. 21 CFR 522.840 - Estradiol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Estradiol. 522.840 Section 522.840 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 DRUGS § 522.840 Estradiol....

  14. 21 CFR 522.840 - Estradiol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Estradiol. 522.840 Section 522.840 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 DRUGS § 522.840 Estradiol....

  15. 21 CFR 522.840 - Estradiol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Estradiol. 522.840 Section 522.840 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 DRUGS § 522.840 Estradiol....

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

    PubMed

    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.

  17. 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.

  18. De novo synthesized estradiol protects against methylmercury-induced neurotoxicity in cultured rat hippocampal slices.

    PubMed

    Yamazaki, Takeshi; Yamamoto, Megumi; Ishihara, Yasuhiro; Komatsu, Shota; Munetsuna, Eiji; Onizaki, Masahiro; Ishida, Atsuhiko; Kawato, Suguru; Mukuda, Takao

    2013-01-01

    Estrogen, a class of female sex steroids, is neuroprotective. Estrogen is synthesized in specific areas of the brain. There is a possibility that the de novo synthesized estrogen exerts protective effect in brain, although direct evidence for the neuroprotective function of brain-synthesized estrogen has not been clearly demonstrated. Methylmercury (MeHg) is a neurotoxin that induces neuronal degeneration in the central nervous system. The neurotoxicity of MeHg is region-specific, and the molecular mechanisms for the selective neurotoxicity are not well defined. In this study, the protective effect of de novo synthesized 17β-estradiol on MeHg-induced neurotoxicity in rat hippocampus was examined. Neurotoxic effect of MeHg on hippocampal organotypic slice culture was quantified by propidium iodide fluorescence imaging. Twenty-four-hour treatment of the slices with MeHg caused cell death in a dose-dependent manner. The toxicity of MeHg was attenuated by pre-treatment with exogenously added estradiol. The slices de novo synthesized estradiol. The estradiol synthesis was not affected by treatment with 1 µM MeHg. The toxicity of MeHg was enhanced by inhibition of de novo estradiol synthesis, and the enhancement of toxicity was recovered by the addition of exogenous estradiol. The neuroprotective effect of estradiol was inhibited by an estrogen receptor (ER) antagonist, and mimicked by pre-treatment of the slices with agonists for ERα and ERβ, indicating the neuroprotective effect was mediated by ERs. Hippocampus de novo synthesized estradiol protected hippocampal cells from MeHg-induced neurotoxicity via ERα- and ERβ-mediated pathways. The self-protective function of de novo synthesized estradiol might be one of the possible mechanisms for the selective sensitivity of the brain to MeHg toxicity.

  19. De Novo Synthesized Estradiol Protects against Methylmercury-Induced Neurotoxicity in Cultured Rat Hippocampal Slices

    PubMed Central

    Ishihara, Yasuhiro; Komatsu, Shota; Munetsuna, Eiji; Onizaki, Masahiro; Ishida, Atsuhiko; Kawato, Suguru; Mukuda, Takao

    2013-01-01

    Background Estrogen, a class of female sex steroids, is neuroprotective. Estrogen is synthesized in specific areas of the brain. There is a possibility that the de novo synthesized estrogen exerts protective effect in brain, although direct evidence for the neuroprotective function of brain-synthesized estrogen has not been clearly demonstrated. Methylmercury (MeHg) is a neurotoxin that induces neuronal degeneration in the central nervous system. The neurotoxicity of MeHg is region-specific, and the molecular mechanisms for the selective neurotoxicity are not well defined. In this study, the protective effect of de novo synthesized 17β-estradiol on MeHg-induced neurotoxicity in rat hippocampus was examined. Methodology/Principal Findings Neurotoxic effect of MeHg on hippocampal organotypic slice culture was quantified by propidium iodide fluorescence imaging. Twenty-four-hour treatment of the slices with MeHg caused cell death in a dose-dependent manner. The toxicity of MeHg was attenuated by pre-treatment with exogenously added estradiol. The slices de novo synthesized estradiol. The estradiol synthesis was not affected by treatment with 1 µM MeHg. The toxicity of MeHg was enhanced by inhibition of de novo estradiol synthesis, and the enhancement of toxicity was recovered by the addition of exogenous estradiol. The neuroprotective effect of estradiol was inhibited by an estrogen receptor (ER) antagonist, and mimicked by pre-treatment of the slices with agonists for ERα and ERβ, indicating the neuroprotective effect was mediated by ERs. Conclusions/Significance Hippocampus de novo synthesized estradiol protected hippocampal cells from MeHg-induced neurotoxicity via ERα- and ERβ-mediated pathways. The self-protective function of de novo synthesized estradiol might be one of the possible mechanisms for the selective sensitivity of the brain to MeHg toxicity. PMID:23405170

  20. Membrane-Initiated Estradiol Signaling Induces Spinogenesis Required for Female Sexual Receptivity

    PubMed Central

    Christensen, Amy; Dewing, Phoebe

    2011-01-01

    Estrogens have profound actions on the structure of the nervous system during development and in adulthood. One of the signature actions of estradiol is to alter the morphology of neural processes. In the hippocampus, estradiol modulates spines and cellular excitability that affect cognitive behaviors. In the hypothalamus, estradiol increases spine density in mediobasal hypothalamic nuclei that regulate reproduction. The hypothalamic arcuate nucleus (ARH), an important site for modulation of female sexual receptivity, has a sexual dimorphism in dendritic spine density that favors females. In the present study, we used both β-actin immunostaining and Golgi staining to visualize estradiol-induced changes in spine density in Long–Evans rats. Golgi impregnation was used to visualize spine shape, and then β-actin immunoreactivity was used as a semiquantitative measure of spine plasticity since actin forms the core of dendritic spines. At 4 h after estradiol treatment, both β-actin immunofluorescence and filopodial spines were increased (from 70.57 ± 1.09% to 78.01 ± 1.05%, p < 0.05). Disruption of estradiol-induced β-actin polymerization with cytochalasin D attenuated lordosis behavior, indicating the importance of estradiol-mediated spinogenesis for female sexual receptivity (81.43 ± 7.05 to 35.00 ± 11.76, p < 0.05). Deactivation of cofilin, an actin depolymerizing factor is required for spinogenesis. Membrane-initiated estradiol signaling involving the metabotropic glutamate receptor 1a was responsible for the phosphorylation and thereby deactivation of cofilin. These data demonstrate that estradiol-induced spinogenesis in the ARH is an important cellular mechanism for the regulation of female sexual behavior. PMID:22131419

  1. Maternal Serum Lipid, Estradiol, and Progesterone Levels in Pregnancy, and the Impact of Placental and Hepatic Pathologies

    PubMed Central

    Pecks, U.; Rath, W.; Kleine-Eggebrecht, N.; Maass, N.; Voigt, F.; Goecke, T. W.; Mohaupt, M. G.; Escher, G.

    2016-01-01

    Objective: Lipids and steroid hormones are closely linked. While cholesterol is the substrate for (placental) steroid hormone synthesis, steroid hormones regulate hepatic lipid production. The aim of this study was to quantify circulating steroid hormones and lipid metabolites, and to characterize their interactions in normal and pathological pregnancies with a focus on hepatic and placental pathologies. Methods: A total of 216 serum samples were analyzed. Group A consisted of 32 patients with uncomplicated pregnancies who were analyzed at three different time-points in pregnancy (from the first through the third trimester) and once post partum. Group B consisted of 36 patients (24th to 42nd week of gestation) with pregnancy pathologies (IUGR n = 10, preeclampsia n = 13, HELLP n = 6, intrahepatic cholestasis n = 7) and 31 controls with uncomplicated pregnancies. Steroid profiles including estradiol, progesterone, and dehydroepiandrosterone were measured by GC-MS and compared with lipid concentrations. Results: In Group A, cholesterol and triglycerides correlated positively with estradiol (cholesterol ρ = 0.50, triglycerides ρ = 0.57) and progesterone (ρ = 0.49, ρ = 0.53) and negatively with dehydroepiandrosterone (ρ = − 0.47, ρ = − 0.38). Smoking during pregnancy affected estradiol concentrations, leading to lower levels in the third trimester compared to non-smoking patients (p < 0.05). In Group B, cholesterol levels were found to be lower in IUGR pregnancies and in patients with HELLP syndrome compared to controls (p < 0.05). Steroid hormone concentrations of estradiol (p < 0.05) and progesterone (p < 0.01) were lower in pregnancies with IUGR. Discussion: Lipid and steroid levels were affected most in IUGR pregnancies, while only minor changes in concentrations were observed for other pregnancy-related disorders. Each of the analyzed entities displayed specific changes. However, since the

  2. Ketogenic diet delays the phase of circadian rhythms and does not affect AMP-activated protein kinase (AMPK) in mouse liver.

    PubMed

    Genzer, Yoni; Dadon, Maayan; Burg, Chen; Chapnik, Nava; Froy, Oren

    2015-12-05

    Ketogenic diet (KD) is used for weight loss or to treat epilepsy. KD leads to liver AMP-activated protein kinase (AMPK) activation, which would be expected to inhibit gluconeogenesis. However, KD leads to increased hepatic glucose output. As AMPK and its active phosphorylated form (pAMPK) show circadian oscillation, this discrepancy could stem from wrong-time-of-day sampling. The effect of KD was tested on mouse clock gene expression, AMPK, mTOR, SIRT1 and locomotor activity for 2 months and compared to low-fat diet (LFD). KD led to 1.5-fold increased levels of blood glucose and insulin. Brain pAMPK/AMPK ratio was 40% higher under KD, whereas that in liver was not affected. KD led to 40% and 20% down-regulation of the ratio of pP70S6K/P70S6K, the downstream target of mTOR, in the brain and liver, respectively. SIRT1 levels were 40% higher in the brain, but 40% lower in the liver of KD-fed mice. Clock genes showed delayed rhythms under KD. In the brain of KD-fed mice, amplitudes of clock genes were down-regulated, whereas 6-fold up-regulation was found in the liver. The metabolic state under KD indicates reduced satiety in the brain and reduced anabolism alongside increased gluconeogenesis in the liver.

  3. Ablation of systemic SIRT1 activity promotes nonalcoholic fatty liver disease by affecting liver-mesenteric adipose tissue fatty acid mobilization

    USDA-ARS?s Scientific Manuscript database

    The incidence of nonalcoholic fatty liver disease (NAFLD) is escalating paralleled with obesity rates in both adults and children. Mammalian sirtuin 1 (SIRT1), a highly conserved NAD+-dependent protein deacetylase, has been identified as a metabolic regulator of lipid homeostasis and a potential tar...

  4. Hernia fibroblasts lack β-estradiol induced alterations of collagen gene expression

    PubMed Central

    2006-01-01

    Background Estrogens are reported to increase type I and type III collagen deposition and to regulate Metalloproteinase 2 (MMP-2) expression. These proteins are reported to be dysregulated in incisional hernia formation resulting in a significantly decreased type I to III ratio. We aimed to evaluate the β-estradiol mediated regulation of type I and type III collagen genes as well as MMP-2 gene expression in fibroblasts derived from patients with or without history of recurrent incisional hernia disease. We compared primary fibroblast cultures from male/female subjects without/without incisional hernia disease. Results Incisional hernia fibroblasts (IHFs) revealed a decreased type I/III collagen mRNA ratio. Whereas fibroblasts from healthy female donors responded to β-estradiol, type I and type III gene transcription is not affected in fibroblasts from males or affected females. Furthermore β-estradiol had no influence on the impaired type I to III collagen ratio in fibroblasts from recurrent hernia patients. Conclusion Our results suggest that β-estradiol does not restore the imbaired balance of type I/III collagen in incisional hernia fibroblasts. Furthermore, the individual was identified as an independent factor for the β-estradiol induced alterations of collagen gene expression. The observation of gender specific β-estradiol-dependent changes of collagen gene expression in vitro is of significance for future studies of cellular response. PMID:17010202

  5. Modulation of SHBG binding to testosterone and estradiol by sex and morbid obesity.

    PubMed

    Grasa, María Del Mar; Gulfo, José; Camps, Núria; Alcalá, Rosa; Monserrat, Laura; Moreno-Navarrete, José María; Ortega, Francisco José; Esteve, Montserrat; Remesar, Xavier; Fernández-López, José Antonio; Fernández-Real, José Manuel; Alemany, Marià

    2017-04-01

    Sex hormone-binding globulin (SHBG) binds and transports testosterone and estradiol in plasma. The possibility that SHBG is a mixture of transporting proteins has been postulated. We analyzed in parallel the effects of obesity status on the levels and binding capacity of circulating SHBG and their relationship with testosterone and estradiol. Anthropometric measures and plasma were obtained from apparently healthy young (i.e. 35 ± 7 years) premenopausal women (n = 32) and men (n = 30), with normal weight and obesity (BMI >30 kg/m(2)). SHBG protein (Western blot), as well as the plasma levels of testosterone, estradiol, cortisol and insulin (ELISA) were measured. Specific binding of estradiol and testosterone to plasma SHBG was analyzed using tritium-labeled hormones. Significant differences in SHBG were observed within the obesity status and gender, with discordant patterns of change in testosterone and estradiol. In men, testosterone occupied most of the binding sites. Estrogen binding was much lower in all subjects. Lower SHBG of morbidly obese (BMI >40 kg/m(2)) subjects affected testosterone but not estradiol. The ratio of binding sites to SHBG protein levels was constant for testosterone, but not for estradiol. The influence of gender was maximal in morbid obesity, with men showing the highest binding/SHBG ratios. The results reported here are compatible with SHBG being a mixture of at least two functionally different hormone-binding globulins, being affected by obesity and gender and showing different structure, affinities for testosterone and estradiol and also different immunoreactivity. © 2017 European Society of Endocrinology.

  6. Cytochrome P450 1A2 Metabolizes 17β-Estradiol to Suppress Hepatocellular Carcinoma

    PubMed Central

    Ren, Jianwai; Chen, George G.; Liu, Yi; Su, Xianwei; Hu, Baoguang; Leung, Billy C. S.; Wang, Y.; Ho, Rocky L. K.; Yang, Shengli; Lu, Gang; Lee, C. G.; Lai, Paul B. S.

    2016-01-01

    Hepatocellular carcinoma (HCC) occurs more frequently in men than in women. It is commonly agreed that estrogen plays important roles in suppressing HCC development, however, the underlying mechanism remains largely unknown. Since estrogen is mainly metabolized in liver and its metabolites affect cell proliferation, we sought to investigate if the liver-specific cytochrome P450 1A2 (CYP1A2) mediated the inhibitory effect of estrogen on HCC. In this study, the expression of estrogen-metabolizing enzyme CYP1A2 was determined in HCC tissues and cell lines. Cell proliferation and apoptosis were assessed in cells with or without CYP1A2 overexpression. The levels of 17β-estradiol (E2) and its metabolite 2-methoxyestradiol (2-ME) were determined. A xenograft tumor model in mice was established to confirm the findings. It was found that CYP1A2 expression was greatly repressed in HCC. E2 suppressed HCC cell proliferation and xenograft tumor development by inducing apoptosis. The inhibitory effect was significantly enhanced in cells with CYP1A2 overexpression, which effectively conversed E2 to the cytotoxic 2-ME. E2 in combination with sorafenib showed an additive effect on HCC. The anti-HCC effect of E2 was not associated with estrogen receptors ERα and ERβ as well as tumor suppressor P53 but enhanced by the approved anti-HCC drug sorafenib. In addition, HDAC inhibitors greatly induced CYP1A2 promoter activities in cancer cells, especially liver cancer cells, but not in non-tumorigenic cells. Collectively, CYP1A2 metabolizes E2 to generate the potent anti-tumor agent 2-ME in HCC. The reduction of CYP1A2 significantly disrupts this metabolic pathway, contributing the progression and growth of HCC and the gender disparity of this malignancy. PMID:27093553

  7. Protein restriction during pregnancy affects maternal liver lipid metabolism and fetal brain lipid composition in the rat.

    PubMed

    Torres, Nimbe; Bautista, Claudia J; Tovar, Armando R; Ordáz, Guillermo; Rodríguez-Cruz, Maricela; Ortiz, Victor; Granados, Omar; Nathanielsz, Peter W; Larrea, Fernando; Zambrano, Elena

    2010-02-01

    Suboptimal developmental environments program offspring to lifelong metabolic problems. The aim of this study was to determine the impact of protein restriction in pregnancy on maternal liver lipid metabolism at 19 days of gestation (dG) and its effect on fetal brain development. Control (C) and restricted (R) mothers were fed with isocaloric diets containing 20 and 10% of casein. At 19 dG, maternal blood and livers and fetal livers and brains were collected. Serum insulin and leptin levels were determinate in mothers. Maternal and fetal liver lipid and fetal brain lipid quantification were performed. Maternal liver and fetal brain fatty acids were quantified by gas chromatography. In mothers, liver desaturase and elongase mRNAs were measured by RT-PCR. Maternal body and liver weights were similar in both groups. However, fat body composition, including liver lipids, was lower in R mothers. A higher fasting insulin at 19 dG in the R group was observed (C = 0.2 +/- 0.04 vs. R = 0.9 +/- 0.16 ng/ml, P < 0.01) and was inversely related to early growth retardation. Serum leptin in R mothers was significantly higher than that observed in C rats (C = 5 +/- 0.1 vs. R = 7 +/- 0.7 ng/ml, P < 0.05). In addition, protein restriction significantly reduced gene expression in maternal liver of desaturases and elongases and the concentration of arachidonic (AA) and docosahexanoic (DHA) acids. In fetus from R mothers, a low body weight (C = 3 +/- 0.3 vs. R = 2 +/- 0.1 g, P < 0.05), as well as liver and brain lipids, including the content of DHA in the brain, was reduced. This study showed that protein restriction during pregnancy may negatively impact normal fetal brain development by changes in maternal lipid metabolism.

  8. 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 following...

  9. 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...

  10. 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...

  11. Chronic ethanol consumption disrupts the core molecular clock and diurnal rhythms of metabolic genes in the liver without affecting the suprachiasmatic nucleus.

    PubMed

    Filiano, Ashley N; Millender-Swain, Telisha; Johnson, Russell; Young, Martin E; Gamble, Karen L; Bailey, Shannon M

    2013-01-01

    Chronic ethanol consumption disrupts several metabolic pathways including β-oxidation and lipid biosynthesis, facilitating the development of alcoholic fatty liver disease. Many of these same metabolic pathways are directly regulated by cell autonomous circadian clocks, and recent studies suggest that disruption of daily rhythms in metabolism contributes to multiple common cardiometabolic diseases (including non-alcoholic fatty liver disease). However, it is not known whether ethanol disrupts the core molecular clock in the liver, nor whether this, in turn, alters rhythms in lipid metabolism. Herein, we tested the hypothesis that chronic ethanol consumption disrupts the molecular circadian clock in the liver and potentially changes the diurnal expression patterns of lipid metabolism genes. Consistent with previous studies, male C57BL/6J mice fed an ethanol-containing diet exhibited higher levels of liver triglycerides compared to control mice, indicating hepatic steatosis. Further, the diurnal oscillations of core clock genes (Bmal1, Clock, Cry1, Cry2, Per1, and Per2) and clock-controlled genes (Dbp, Hlf, Nocturnin, Npas2, Rev-erbα, and Tef) were altered in livers from ethanol-fed mice. In contrast, ethanol had only minor effects on the expression of core clock genes in the suprachiasmatic nucleus (SCN). These results were confirmed in Per2(Luciferase) knock-in mice, in which ethanol induced a phase advance in PER2::LUC bioluminescence oscillations in liver, but not SCN. Further, there was greater variability in the phase of PER2::LUC oscillations in livers from ethanol-fed mice. Ethanol consumption also affected the diurnal oscillations of metabolic genes, including Adh1, Cpt1a, Cyp2e1, Pck1, Pdk4, Ppargc1a, Ppargc1b and Srebp1c, in the livers of C57BL/6J mice. In summary, chronic ethanol consumption alters the function of the circadian clock in liver. Importantly, these results suggest that chronic ethanol consumption, at levels sufficient to cause steatosis

  12. Chronic Ethanol Consumption Disrupts the Core Molecular Clock and Diurnal Rhythms of Metabolic Genes in the Liver without Affecting the Suprachiasmatic Nucleus

    PubMed Central

    Filiano, Ashley N.; Millender-Swain, Telisha; Johnson, Russell; Young, Martin E.; Gamble, Karen L.; Bailey, Shannon M.

    2013-01-01

    Chronic ethanol consumption disrupts several metabolic pathways including β-oxidation and lipid biosynthesis, facilitating the development of alcoholic fatty liver disease. Many of these same metabolic pathways are directly regulated by cell autonomous circadian clocks, and recent studies suggest that disruption of daily rhythms in metabolism contributes to multiple common cardiometabolic diseases (including non-alcoholic fatty liver disease). However, it is not known whether ethanol disrupts the core molecular clock in the liver, nor whether this, in turn, alters rhythms in lipid metabolism. Herein, we tested the hypothesis that chronic ethanol consumption disrupts the molecular circadian clock in the liver and potentially changes the diurnal expression patterns of lipid metabolism genes. Consistent with previous studies, male C57BL/6J mice fed an ethanol-containing diet exhibited higher levels of liver triglycerides compared to control mice, indicating hepatic steatosis. Further, the diurnal oscillations of core clock genes (Bmal1, Clock, Cry1, Cry2, Per1, and Per2) and clock-controlled genes (Dbp, Hlf, Nocturnin, Npas2, Rev-erbα, and Tef) were altered in livers from ethanol-fed mice. In contrast, ethanol had only minor effects on the expression of core clock genes in the suprachiasmatic nucleus (SCN). These results were confirmed in Per2Luciferase knock-in mice, in which ethanol induced a phase advance in PER2::LUC bioluminescence oscillations in liver, but not SCN. Further, there was greater variability in the phase of PER2::LUC oscillations in livers from ethanol-fed mice. Ethanol consumption also affected the diurnal oscillations of metabolic genes, including Adh1, Cpt1a, Cyp2e1, Pck1, Pdk4, Ppargc1a, Ppargc1b and Srebp1c, in the livers of C57BL/6J mice. In summary, chronic ethanol consumption alters the function of the circadian clock in liver. Importantly, these results suggest that chronic ethanol consumption, at levels sufficient to cause steatosis

  13. 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.

  14. Changes in hippocampal function of ovariectomized rats after sequential low doses of estradiol to simulate the preovulatory estrogen surge

    PubMed Central

    Scharfman, Helen E.; Hintz, Tana M.; Gomez, Juan; Stormes, Kerry A.; Barouk, Sharon; Malthankar-Phatak, Gauri H.; McCloskey, Daniel P.; Luine, Victoria N.; MacLusky, Neil J.

    2008-01-01

    In adult female rats, robust hippocampal changes occur when estradiol rises on the morning of proestrus. Whether estradiol mediates these changes, however, remains unknown. To address this issue, we used sequential injections of estradiol to simulate two key components of the preovulatory surge: the rapid rise in estradiol on proestrous morning, and the slower rise during the preceding day, diestrus 2. Animals were examined mid-morning of simulated proestrus, and compared to vehicle-treated or intact rats. In both simulated and intact rats, CA1-evoked responses were potentiated in hippocampal slices, and presynaptic mechanisms appeared to contribute. In CA3, multiple population spikes were evoked in response to mossy fiber stimuli, and expression of brain-derived neurotrophic factor was increased. Simulation of proestrous morning also improved performance on object and place recognition tests, in comparison to vehicle treatment. Surprisingly, effects on CA1-evoked responses showed a dependence on estradiol during simulated diestrus 2, as well as a dependence on proestrous morning. Increasing estradiol above the physiological range on proestrous morning paradoxically decreased evoked responses in CA1. However, CA3 pyramidal cell activity increased further, and became synchronized. Together, the results confirm that physiological estradiol levels are sufficient to profoundly affect hippocampal function. In addition: (i) changes on proestrous morning appear to depend on slow increases in estradiol during the preceding day; (ii) effects are extremely sensitive to the peak serum level on proestrous morning; and (iii) there are striking subfield differences within the hippocampus. PMID:17970745

  15. Ozone-derived Oxysterols Affect Liver X Receptor (LXR) Signaling: A POTENTIAL ROLE FOR LIPID-PROTEIN ADDUCTS.

    PubMed

    Speen, Adam M; Kim, Hye-Young H; Bauer, Rebecca N; Meyer, Megan; Gowdy, Kymberly M; Fessler, Michael B; Duncan, Kelly E; Liu, Wei; Porter, Ned A; Jaspers, Ilona

    2016-11-25

    When inhaled, ozone (O3) interacts with cholesterols of airway epithelial cell membranes or the lung-lining fluid, generating chemically reactive oxysterols. The mechanism by which O3-derived oxysterols affect molecular function is unknown. Our data show that in vitro exposure of human bronchial epithelial cells to O3 results in the formation of oxysterols, epoxycholesterol-α and -β and secosterol A and B (Seco A and Seco B), in cell lysates and apical washes. Similarly, bronchoalveolar lavage fluid obtained from human volunteers exposed to O3 contained elevated levels of these oxysterol species. As expected, O3-derived oxysterols have a pro-inflammatory effect and increase NF-κB activity. Interestingly, expression of the cholesterol efflux pump ATP-binding cassette transporter 1 (ABCA1), which is regulated by activation of the liver X receptor (LXR), was suppressed in epithelial cells exposed to O3 Additionally, exposure of LXR knock-out mice to O3 enhanced pro-inflammatory cytokine production in the lung, suggesting LXR inhibits O3-induced inflammation. Using alkynyl surrogates of O3-derived oxysterols, our data demonstrate adduction of LXR with Seco A. Similarly, supplementation of epithelial cells with alkynyl-tagged cholesterol followed by O3 exposure causes observable lipid-LXR adduct formation. Experiments using Seco A and the LXR agonist T0901317 (T09) showed reduced expression of ABCA1 as compared with stimulation with T0901317 alone, indicating that Seco A-LXR protein adduct formation inhibits LXR activation by traditional agonists. Overall, these data demonstrate that O3-derived oxysterols have pro-inflammatory functions and form lipid-protein adducts with LXR, thus leading to suppressed cholesterol regulatory gene expression and providing a biochemical mechanism mediating O3-derived formation of oxidized lipids in the airways and subsequent adverse health effects.

  16. Promotion of human adipocyte precursor replication by 17beta-estradiol in culture.

    PubMed Central

    Roncari, D A; Van, R L

    1978-01-01

    The influence of 17beta-estradiol and 17alpha-estradiol on adult human omental adipocyte precursors grown in a propagating culture system was studied. Cells were grown in subculture in the presence or absence of hormone. 17beta-estradiol resulted in significant promotion of adipocyte precursor replication, as determined by cell counting and incorporation of radioactive thymidine into DNA. The hormone stimulated cell multiplication in the concentration range 0.5--500 ng/ml growth medium. The highest level tested was 500 ng/ml. The maximal effects were obtained at 50 ng/ml (P less than 0.001 by paired t test, 48 h after hormone addition). All 10 cell strains (five were derived from men and five from women) that were tested responded similarly to the hormone. 17beta-estradiol did not affect cell size. 17alpha-estradiol did not promote the replication of adipocyte precursors, nor did it influence cell size. Thus, 17beta-estradiol, which is the active isomer in known target tissues, stimulates the multiplication of human adipocyte precursors in culture. Images PMID:690182

  17. Altered functional brain asymmetry for mental rotation: effect of estradiol changes across the menstrual cycle

    PubMed Central

    Zhu, Xun; Kelly, Thomas H.; Curry, Thomas E.; Lal, Chitra; Joseph, Jane E.

    2015-01-01

    Mental rotation is a visuo-spatial task associated with pronounced sex differences. Performance is also affected by gonadal hormones such as testosterone and estradiol. To better understand hormonal modulation of the neural substrates of mental rotation, the present study examined the influence of estradiol using functional magnetic resonance imaging. Ten pre-menopausal women were tested on a 3D mental rotation task during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle. Change in estradiol between the two phases was confirmed by hormone assays. Brain activation patterns were similar across the two phases, but the change in estradiol had different associations with the two hemispheres. Better performance in the LF than the EF phase was associated with a pattern of reduced recruitment of the right hemisphere and increased recruitment of the left hemisphere. The increased recruitment of the left hemisphere was directly associated with greater changes in estradiol. Given that the right hemisphere is the dominant hemisphere in visuo-spatial processing, our results suggest that estradiol is associated with reduced functional asymmetry, consistent with recent accounts of hormonal modulation of neurocognitive function. PMID:26222958

  18. Altered functional brain asymmetry for mental rotation: effect of estradiol changes across the menstrual cycle.

    PubMed

    Zhu, Xun; Kelly, Thomas H; Curry, Thomas E; Lal, Chitra; Joseph, Jane E

    2015-09-30

    Mental rotation is a visuospatial task associated with pronounced sex differences. Performance is also affected by gonadal hormones such as testosterone and estradiol. To better understand hormonal modulation of the neural substrates of mental rotation, the present study examined the influence of estradiol using functional MRI. Ten premenopausal women were tested on a 3D mental rotation task during the early follicular and late follicular phases of the menstrual cycle. Change in estradiol between the two phases was confirmed by hormone assays. Brain activation patterns were similar across the two phases, but the change in estradiol had different associations with the two hemispheres. Better performance in the late follicular than the early follicular phase was associated with a pattern of reduced recruitment of the right hemisphere and increased recruitment of the left hemisphere. The increased recruitment of the left hemisphere was directly associated with greater changes in estradiol. Given that the right hemisphere is the dominant hemisphere in visuospatial processing, our results suggest that estradiol is associated with reduced functional asymmetry, consistent with recent accounts of hormonal modulation of neurocognitive function.

  19. 17β-estradiol enhances memory duration in the main olfactory bulb in CD-1 mice.

    PubMed

    Dillon, T Samuel; Fox, Laura C; Han, Crystal; Linster, Christiane

    2013-12-01

    Rodents rely heavily on odor detection, discrimination, and memory to locate food, find mates, care for pups, and avoid predators. Estrogens have been shown to increase memory retention in rodents performing spatial memory and object placement tasks. Here we evaluate the extent to which 17β-estradiol modulates memory formation and duration in the olfactory system. Adult CD-1 mice were gonadectomized and given either systemic 17β-estradiol replacement, local 17β-estradiol in the main olfactory bulb, or no replacement. Before performing the behavioral task the mice were given saline or PHTPP (an estrogen receptor β [ER-β] antagonist) via bilateral infusion into the main olfactory bulb. As the beta-type estrogen receptor (ER-β) is more abundant than the alpha-type estrogen receptor in the murine main olfactory bulb, the current study focuses on 17β-estradiol and its interactions with ERβ. Habituation, a simple, nonassociative learning task in which an animal is exposed to the same odor over successive presentations, was used to evaluate the animals' ability to detect odors and form an olfactory memory. To evaluate memory duration, we added a final trial of intertrial interval time (30 or 60 min) in which we presented the habituated odor. Neither surgical nor drug manipulation affected the ability of mice to detect or habituate to an odor. After habituation, gonadectomized 17β-estradiol-treated mice retained memory of an odor for 30 min, whereas non-estradiol-treated, 17β-estradiol+ERβ antagonist (PHTPP), and untreated male mice did not remember an odor 30 min after habituation. The results show that both systemic and local bulbar infusions of 17β-estradiol enhance odor memory duration in mice.

  20. Ethinyl Estradiol and Etonogestrel Vaginal Ring

    MedlinePlus

    ... a class of medications called combination hormonal contraceptives (birth control medications). Etonogestrel is a progestin and ethinyl estradiol ... contraceptive ring is a very effective method of birth control but does not prevent the spread of human ...

  1. Estradiol valerate and tibolone: effects on memory.

    PubMed

    Aguiar, R B de; Dickel, O E; Cunha, R W; Monserrat, J M; Barros, D M; Martinez, P E

    2006-12-01

    This study investigated the effects of estradiol valerate (EV) and tibolone (TB) treatments on some memory parameters of ovariectomized young (2 months), adult (8 months) and old (20 months) female rats. A Sham-operated group was used as control and the animals were treated daily, by oral gavage, with saline (Sham and placebo NR group), EV (0.3 mg/kg) or TB (0.5 or 1 mg/kg, TB1 and TB2, respectively). In step-down inhibitory avoidance task, the latency of old TB2-treated females in the short-term test was significantly inferior (p<0.05), compared to TB2 adults. In the elevated plus maze, adult NR females spent significantly less time (p<0.05) in the open arms as compared with EV and TB2-treated animals. Additionally, adult TB2-treated females spent significantly less time in the closed arms compared to Sham, NR and TB1 groups. Finally, in the water maze retention test, young TB1-treated animals performed worse when compared to Sham, EV and TB2 females. In the old animals, EV treatment hampered subject performance as compared to all other treatments. Taken together, these results indicate that ovarian hormones differently affect female memory in an age-dependent manner.

  2. A pilot study estimating liver fibrosis with ultrasound shear-wave elastography: does the cause of liver disease or location of measurement affect performance?

    PubMed

    Beland, Michael D; Brown, Sanford F; Machan, Jason T; Taliano, Ross J; Promrat, Kittichai; Cronan, John J

    2014-09-01

    The purpose of this study was to evaluate the diagnostic accuracy of real-time shear-wave elastography for assessment of liver fibrosis in an unselected patient population, comparing shear-wave elastography measurements obtained at and remote from the site of random liver biopsy. In a prospective study of 50 patients (21 with and 29 without hepatitis C) referred for clinically indicated random liver biopsy for diffuse liver disease, shear-wave elastography measurements were taken from four locations before biopsy: one at the left lobe, two at the right lobe, and one at the biopsy location. The mean, minimum, maximum, and SD of shear-wave elastography were compared with pathologic grading. Steatosis and serum markers were analyzed using multiple logistic regression. Optimized shear-wave elastography thresholds were calculated using AUC analysis. The AUC (95% CI) at the biopsy site, ipsilateral lobe, and contralateral lobe were 0.82 (0.63-1.0), 0.84 (0.67-1.0), and 0.59 (0.19-0.99) in hepatitis C patients; 0.89 (0.75-1.0), 0.88 (0.73-1.0), and 0.93 (0.80-1.0) in nonhepatitis C patients; and 0.85 (0.74-0.96), 0.89 (0.79-0.99), and 0.80 (0.67-0.93) in all patients, respectively. Optimized biopsy site shear-wave elastography values for detecting Metavir score F2 or greater were 1.87 m/s (75% sensitivity and specificity), 2.00 m/s (80% sensitivity and specificity), and 1.89 m/s (76% sensitivity and specificity) in hepatitis C, nonhepatitis C, and all patients, respectively. Steatosis and serum markers were not significant. Real-time shear-wave elastography accurately predicted significant fibrosis (stage ≥ 2) in an unselected patient population with diffuse disease, including patients with and without hepatitis C. Shear-wave elastography best predicts pathologic grading when taken at the biopsy site or ipsilateral lobe in hepatitis C patients. Percentage steatosis was not predictive of shear-wave elastography results.

  3. Liver metastases

    MedlinePlus

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver metastases

  4. Multivariate analysis of the factors affecting attitude toward living liver donation among workers in surgical services in Spanish, Mexican, and Cuban hospitals.

    PubMed

    Ríos, A; López-Navas, A; Ayala-García, M A; Sebastián, M J; Abdo-Cuza, A; Febrero, B; Ramírez, E J; Muñoz, G; Palacios, G; Suárez-López, J; Castellanos, R; Rodríguez, J S; Martínez, M A; Nieto, A; Martínez-Alarcón, L; Ramis, G; Ramírez, P; Parrilla, P

    2012-01-01

    Current liver donation rates are insufficient to cover transplant needs. Therefore, it is essential to promote living liver donation (LLD) given the ever decreasing morbidity and mortality in the donor and the improving results in the recipient. LLD is becoming increasingly accepted. However, in the health care system, a percentage of the personnel are not in favor. To analyze the attitude of personnel in surgical services in Spain and Latin-America hospitals toward LLD. As part of the "International Collaborative Donor Project," a random sample was taken and stratified according to surgical service and job category in 10 hospitals; three in Spain, five in Mexico, and two in Cuba (n = 496). Attitude was evaluated using a validated survey that was completed anonymously and self-administered. Eighty-six percent (n = 425) of respondents were in favor of related living liver donation, and 30% (n = 147) were in favor if it were not related. According to country, 88% of the Mexican respondents were in favor of living liver donation, 85% of the Cubans, and 82% of the Spanish (P > .05). In the multivariate analysis of the variables with most weight affecting attitude toward LLD, the following significant associations were found: (1) a favourable attitude toward living kidney donation (odds ratio [OR] = 91; P < .001); (2) acceptance of a donated living liver if one were needed (OR = 11; P < .001); and (3) family discussion about donation and transplantation (OR = 2.581; P = .037). Attitude toward related living liver donation was very favorable among hospital personnel in Spanish and Latin American surgical services. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Testosterone-derived estradiol production by male endothelium is robust and dependent on p450 aromatase via estrogen receptor alpha.

    PubMed

    Villablanca, Amparo C; Tetali, Sarada; Altman, Robin; Ng, Kenneth F; Rutledge, John C

    2013-12-01

    Vascular endothelium expresses both the estrogen receptors (ERs) α and β, and ERα mediates development of early atherosclerosis in male mice. This process is thought to be testosterone-dependent. We hypothesized that male murine aortic endothelium produces robust levels of estradiol by aromatase conversion of testosterone, and that regulation of this process is mediated by the presence of ERs, primarily ERα. Aortic endothelium was isolated from ERα knockout (ERα -/-) and wild-type (ERα +/+) male mice and treated with testosterone or the 5α reduction product dihydrotestosterone (DHT), with or without the P450 aromatase inhibitor anastrazole, or a non-specific estrogen receptor antagonist. Aromatase gene expression and estradiol production were assayed. Treatment with testosterone, but not DHT, caused increased aromatase expression and estradiol production in ERα +/+ endothelium that was attenuated by disruption of ERα in the ERα -/- group. Anastrazole inhibition of aromatase reduced testosterone-induced aromatase expression and estradiol levels in both ERα -/- and ERα +/+ endothelium. Antagonism of both ERs decreased testosterone-induced aromatase expression in both wild-type and knockout groups. The effects of the receptor antagonist on estradiol production differed between the two groups, however, with a reduction in estradiol release from the ERα +/+ cells and complete abolition of estradiol release from the ERα -/- cells. Thus, estradiol production in vascular endothelium from male mice is robust, depends on the aromatic conversion of testosterone and requires functional ERα to achieve maximal levels of estradiol generation. Local vascular production of aromatase-mediated estradiol in response to circulating testosterone may affect ERα-dependent mechanisms to increase susceptibility to early atheroma formation in male mice. This pathway may have important therapeutic relevance for reducing the risk of atherosclerotic cardiovascular disease in

  6. Reproduction Does Not Adversely Affect Liver Mitochondrial Respiratory Function but Results in Lipid Peroxidation and Increased Antioxidants in House Mice.

    PubMed

    Mowry, Annelise V; Kavazis, Andreas N; Sirman, Aubrey E; Potts, Wayne K; Hood, Wendy R

    2016-01-01

    Reproduction is thought to come at a cost to longevity. Based on the assumption that increased energy expenditure during reproduction is associated with increased free-radical production by mitochondria, oxidative damage has been suggested to drive this trade-off. We examined the impact of reproduction on liver mitochondrial function by utilizing post-reproductive and non-reproductive house mice (Mus musculus) living under semi-natural conditions. The age-matched post-reproductive and non-reproductive groups were compared after the reproductive females returned to a non-reproductive state, so that both groups were in the same physiological state at the time the liver was collected. Despite increased oxidative damage (p = 0.05) and elevated CuZnSOD (p = 0.002) and catalase (p = 0.04) protein levels, reproduction had no negative impacts on the respiratory function of liver mitochondria. Specifically, in a post-reproductive, maintenance state the mitochondrial coupling (i.e., respiratory control ratio) of mouse livers show no negative impacts of reproduction. In fact, there was a trend (p = 0.059) to suggest increased maximal oxygen consumption by liver mitochondria during the ADP stimulated state (i.e., state 3) in post-reproduction. These findings suggest that oxidative damage may not impair mitochondrial respiratory function and question the role of mitochondria in the trade-off between reproduction and longevity. In addition, the findings highlight the importance of quantifying the respiratory function of mitochondria in addition to measuring oxidative damage.

  7. Differential TGFβ pathway targeting by miR-122 in humans and mice affects liver cancer metastasis

    PubMed Central

    Yin, Shenyi; Fan, Yu; Zhang, Hanshuo; Zhao, Zhihua; Hao, Yang; Li, Juan; Sun, Changhong; Yang, Junyu; Yang, Zhenjun; Yang, Xiao; Lu, Jian; Xi, Jianzhong Jeff

    2016-01-01

    Downregulation of a predominantly hepatocyte-specific miR-122 is associated with human liver cancer metastasis, whereas miR-122-deficient mice display normal liver function. Here we show a functional conservation of miR-122 in the TGFβ pathway: miR-122 target site is present in the mouse but not human TGFβR1, whereas a noncanonical target site is present in the TGFβ1 5′UTR in humans and other primates. Experimental switch of the miR-122 target between the receptor TGFβR1 and the ligand TGFβ1 changes the metastatic properties of mouse and human liver cancer cells. High expression of TGFβ1 in human primary liver tumours is associated with poor survival. We identify over 50 other miRNAs orthogonally targeting ligand/receptor pairs in humans and mice, suggesting that these are evolutionarily common events. These results reveal an evolutionary mechanism for miRNA-mediated gene regulation underlying species-specific physiological or pathological phenotype and provide a potentially valuable strategy for treating liver-associated diseases. PMID:26987776

  8. Current Metabolic Status Affects Urinary Liver-Type Fatty-Acid Binding Protein in Normoalbuminuric Patients With Type 2 Diabetes

    PubMed Central

    Ito, Hiroyuki; Yamashita, Hitomi; Nakashima, Mina; Takaki, Akifusa; Yukawa, Chiduko; Matsumoto, Suzuko; Omoto, Takashi; Shinozaki, Masahiro; Nishio, Shinya; Abe, Mariko; Antoku, Shinichi; Mifune, Mizuo; Togane, Michiko

    2017-01-01

    Background We aimed to study the association between urinary liver-type fatty acid-binding protein (L-FABP), a biomarker of tubulointerstitial injury, and the clinical characteristics of normoalbuminuric and albuminuric patients with type 2 diabetes in order to detect the factors affecting urinary L-FABP. Methods Urinary L-FABP levels were measured in 788 patients with type 2 diabetes and again in 666 patients at 6 months after the initial measurement. The association between the urinary L-FABP level and the clinical parameters was investigated in a retrospective cross-sectional study and a subsequent observation. Results The HbA1c (odds ratio (OR): 1.42; 95% confidence interval (CI): 1.11 - 1.79; P < 0.01), systolic blood pressure (OR: 1.03; 95% CI: 1.01 - 1.05; P < 0.01) levels and estimated glomerular filtration rate (OR: 0.98; 95% CI: 0.96 - 1.00; P = 0.01) were significantly associated with the high levels of urinary L-FABP (> 8.4 μg/gCr) in normoalbuminuric patients. However, a logistic regression analysis revealed that use of renin-angiotensin system (RAS) inhibitors (OR: 2.22; 95% CI: 1.16 - 4.89; P = 0.02), urinary albumin-to-creatinine ratio (ACR) (OR: 1.01; 95% CI: 1.00 - 1.01; P < 0.01) and serum HDL-cholesterol concentration (OR: 0.33; 95% CI: 0.11 - 0.89; P = 0.03) were significantly associated in albuminuric patients. In the follow-up observation, the change in urinary L-FABP was found to be significantly (P < 0.01) influenced by the change in the HbA1c level in both the normoalbuminuric and albuminuric patients. Conclusions High urinary L-FABP is associated with part of the current metabolic abnormalities, including high levels of HbA1c and systolic blood pressure among normoalbuminuric patients with type 2 diabetes. PMID:28270898

  9. Gill and liver histopathological changes in yellow perch (Perca flavescens) and goldfish (Carassius auratus) exposed to oil sands process-affected water.

    PubMed

    Nero, V; Farwell, A; Lister, A; Van der Kraak, G; Lee, L E J; Van Meer, T; MacKinnon, M D; Dixon, D G

    2006-03-01

    The extraction of bitumen from the Athabasca oil sands (Alberta, Canada) produces significant volumes of process-affected water containing elevated levels of naphthenic acids (NAs), ions, and polycyclic aromatic hydrocarbons (PAHs). The sublethal response of aquatic organisms exposed to oil sands constituents in experimental aquatic environments that represent possible reclamation options has been studied. In this study, the effects of process-affected waters on gill and liver tissues in yellow perch (Perca flavescens) and caged goldfish (Carassius auratus) held in several reclamation ponds at Syncrude's Mildred Lake site have been assessed. Following a 3-week exposure, significant gill (epithelial cell necrosis, mucous cell proliferation) and liver (hepatocellular degeneration, inflammatory cell infiltration) histopathological changes were noted in fish held in waters containing high levels of oil sands process-affected water. In addition, measurements of gill dimensions (gill morphometrical indices) proved sensitive and provided evidence of a physiological disturbance (gas exchange) with exposure to oil sands materials. Due to the complexity of oil sands process-affected water, the cause of the alterations could not be attributed to specific oil sands constituents. However, the histopathological parameters were strong indicators of exposure to oil sands process-affected water and morphometrical data were sensitive indicators of pathological response, which can be used to identify the interactive effects of ionic content, NAs, and PAHs in future laboratory studies.

  10. Melatonin affects conjugation of 4-hydroxynonenal with glutathione in liver of pacu, a hypoxia-tolerant fish.

    PubMed

    Bastos, F F; Tobar, S A L; Dantas, R F; Silva, E S; Nogueira, N P A; Paes, M C; Righi, B D P; Bastos, J Cunha; Bastos, V L F Cunha

    2013-10-01

    In cytosol from liver of pacu, Piaractus mesopotamicus, a hypoxia-tolerant fish that dwells in Pantanal, we found an enzyme activity capable of modulating the alkenal 4-hydroxy-2-nonenal (HNE) by conjugating it with glutathione (GST-HNE activity). HNE is a downstream metabolite from the oxidation of polyunsaturated fatty acids by reactive oxygen species arisen from mitochondria of animal cells. HNE production may increase more intensively under oxidative stress. Harmful effects to cell survival may occur when HNE increases over 10(-4) M. Pacus submitted to hypoxia in July (cold season in Pantanal) showed 40% less of this GST-HNE conjugating activity in their liver cytosol. Injecting pacus subjected to hypoxia during the cold season with a summer physiological dose of melatonin caused their liver cytosolic GST-HNE activity to increase up to the levels found in the warm season. From October to March (warm season in Pantanal), pacus are prone to oxidative stress particularly during potamodromous active oxygen-demanding swimming, when they migrate up rivers to spawn. Thus, our findings point out that the higher levels of melatonin in circulation during the summer are important to avoid the increase of 4-HNE inside liver cells of this fish species.

  11. Feeding of potato, tomato and eggplant alkaloids affects food consumption and body and liver weights in mice.

    PubMed

    Friedman, M; Henika, P R; Mackey, B E

    1996-04-01

    Reduced liver weight was used to evaluate the potential toxicity in mice of four naturally occurring steroidal glycoalkaloids: alpha-chaconine and alpha-solanine, alpha-tomatine and solasonine. Increased liver weights was used to evaluate the three corresponding steroidal aglycones: solanidine, tomatidine, and solasodine and the non-alkaloid adrenal steroid dehydroepiandrosterone (DHEA). Adult female Swiss-Webster mice were fed diets containing test compound concentrations of 0 (control), 1.2, 2.4 or 4.8 mmol/kg diet for 7, 14 or 28 d. Absolute liver weights (LW) and relative liver weights (liver weight/body weight x 100, %LW/BW) were determined at autopsy. The %LW/BW was lower than that of controls in mice fed the potato glycoalkaloid alpha-chaconine (-10%, P < or = 0.05) for 7 d with the 2.4 mmol/kg diet dose. Under these same conditions, %LW/BW was greater than that of controls in mice fed two aglycones: solanidine (27%, P < or = 0.001) and solasodine (8%, P < or = 0.01). Relative liver weight increases induced by the aglycones were determined under time and dose conditions in which differences in body weight and food consumption were not significant (2.4 mmol/kg diet for 28 d). Under these conditions, the observed %LW/BW increases relative to the controls were as follows: solanidine (32%, P < or = 0.001), solasodine (22%, P < or = 0.001) and DHEA (16%, P < or = 0.001). Solanidine, solasodine and DHEA were equally potent and were more potent than tomatidine. We also observed that the greater %LW/BW in mice fed 2.4 mmol/kg diet solasodine or solanidine for 14 d declined to near control values if they were fed control diets for another 14 d. The increase in relative liver weight induced by solanidine and solasodine is a reversible adaptive response. These findings and the apparent effects of structure on biological activity should serve as a guide for the removal of the most toxic ++compounds from plant foods. The implications of the results for food safety and

  12. Liver transplant

    MedlinePlus

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  13. Estradiol-17beta and dihydrotestosterone differentially regulate vitellogenin and insulin-like growth factor-I production in primary hepatocytes of the tilapia Oreochromis mossambicus.

    PubMed

    Riley, Larry G; Hirano, Tetsuya; Grau, E Gordon

    2004-06-01

    Effects of estradiol-17beta (E2) and 5alpha-dihydrotestosterone (DHT) on the production of vitellogenin (Vg), insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGFBPs) were examined in vitro using primary hepatocyte culture of the tilapia. Estradiol produced a significant and concentration-related stimulation of Vg release and concomitant, concentration-related reduction in IGF-I mRNA expression in both male and female hepatocytes. In male hepatocytes, DHT significantly increased IGF-I expression, whereas DHT inhibited IGF-I expression and stimulated Vg release in female hepatocytes. Estradiol treatment significantly reduced the release of 25 kDa IGFBP, while stimulating the release of 30 kDa IGFBP from male hepatocytes. In female hepatocytes, E2 significantly increased both 25 and 30 kDa IGFBPs. In male hepatocytes, DHT significantly reduced 25 kDa IGFBP without affecting 30 kDa IGFBP. Conversely, DHT treatment of hepatocytes from female fish significantly increased both the 25 and 30 kDa IGFBPs. The different growth rates observed between male and female tilapia may be a result of gonadal steroid hormones eliciting direct and antagonistic effects on production of IGF-I (growth) and Vg (reproduction) in the liver. Indeed, the different growth patterns likely result from a difference in the sensitivity of male and female hepatocytes to gonadal steroid hormones. These results also indicate direct effects of gonadal steroid hormones on production of IGFBPs, which may play a role in regulating IGF-I mediated growth.

  14. Effects of chronic estradiol treatment on the thyroid gland structure and function of ovariectomized rats.

    PubMed

    Abdel-Dayem, Menna M; Elgendy, Mohamed S

    2009-08-30

    Estrogen therapy is widely used nowadays in women to treat many postmenopausal symptoms but it may have some undesirable effects due to multiple organs affection. So, the aim of this study was to determine the effects of chronic estradiol treatment on the structure and function of the thyroid gland in ovarictomized rats as a model simulating menopause. Thirty adult female Wistar rats divided into three groups were used in this study; the first group was sham-operated, while the second and third groups were ovariectomized. The first and second groups were injected with olive oil while the third group was injected with estradiol dipropionate daily for three months, after that; hormonal assay for T3, T4, TSH and specimens of the thyroid were taken and processed to be examined by light and electron microscopy. The results of this study revealed that serum levels of T3 and T4 decreased in ovariectomized animals and significantly increased after estradiol treatment, while TSH increased in ovariectomized animals and decreased with estradiol treatment. Histological and morphometric study in ovariectomized group revealed marked accumulation of colloid in follicular lumens with decreased epithelial height in addition to increased connective tissue amount. After estradiol treatment the follicles became smaller in size, having small amount of colloid with increased epithelial height in addition to decreased connective tissue content. Ultrastructural study supported these results in addition to the presence of large amount of intracytoplasmic colloid vesicles after estradiol treatment. Low estrogen level may lead to mild thyroidal hypofunction while estradiol treatment may lead to hyperactivity so it should be used very cautiously in the treatment of postmenopausal symptoms to avoid its undesirable stimulatory effect on the thyroid.

  15. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Peripheral microvascular vasodilatory response to estradiol and genistein in women with insulin resistance

    PubMed Central

    Wenner, Megan M.; Taylor, Hugh S.; Stachenfeld, Nina S.

    2015-01-01

    Objective Estradiol enhances vasodilation in healthy women, but vascular effects of the phytoestrogen genistein are still under investigation. Insulin resistance (IR) compromises microvascular function. We therefore examined the interaction of estradiol, genistein, and IR on microvascular vasodilatory responsiveness. Methods We hypothesized that estradiol and genistein increase microvascular vasodilation in healthy women (control, n=8, 23±2 yr, BMI 25.9±2.9 kg/m2) but not in women with IR (n=7, 20±1 yr, BMI 27.3±3.0 kg/m2). We used the cutaneous circulation as a model of microvascular vasodilatory function. We determined cutaneous vascular conductance (CVC) with laser Doppler flowmetry and beat-to-beat blood pressure during local cutaneous heating (42°C) with estradiol or genistein microdialysis perfusions. Because heat induced vasodilation is primarily an NO mediated response, we examined microvascular vasodilation with and without L-NMMA. Results In control women, estradiol enhanced CVC (94.4±2.6 % vs. saline 81.6±4.2 % CVCmax, P<0.05), which was reversed with L-NMMA (80.9±7.8 % CVCmax, P<0.05), but genistein did not affect vasodilation. Neither estradiol nor genistein altered CVC in IR, although L-NMMA attenuated CVC during genistein. Conclusions Our study does not support improved microvascular responsiveness during genistein exposure in healthy young women, and demonstrates that neither estradiol nor genistein improve microvascular vasodilatory responsiveness in women with IR. PMID:25996650

  17. Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethindrone.

    PubMed

    Trapnell, C B; Donahue, S R; Collins, J M; Flockhart, D A; Thacker, D; Abernethy, D R

    1998-12-01

    To evaluate the effect of thalidomide on the plasma pharmacokinetics of ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone). Ten women who had undergone surgical sterilization were enrolled in an open-label crossover study conducted in the Georgetown University Clinical Research Center. The pharmacokinetics of single doses of 0.07 mg ethinyl estradiol and 2 mg norethindrone were measured at baseline and after 3 weeks of 200 mg thalidomide. Compliance with the thalidomide regimen was assessed with use of Medication Event Monitoring System (MEMS) caps. No changes were observed in the pharmacokinetics of ethinyl estradiol or norethindrone with thalidomide therapy. The mean +/- SD area under the plasma concentration-time curve (AUC0-infinity) for ethinyl estradiol was 6580 +/- 1100 ng.h/L at baseline and 5970 +/- 1560 ng.h/L after the thalidomide regimen (paired t test, P > .05). The values for norethindrone were 103 +/- 54 micrograms.h/L and 107 +/- 58 micrograms.h/L (paired t test, P > .05). No changes were observed for other pharmacokinetic parameters assessed for either ethinyl estradiol or norethindrone. No accumulation of thalidomide was seen after 21 days of therapy: day 1 AUC0-infinity 41.1 +/- 13.9 micrograms.h/mL; day 21 AUC0-infinity 59.6 +/- 27.3 micrograms.h/mL (paired t test, P > .05). No changes were observed for other pharmacokinetic parameters assessed for thalidomide between days 1 and 21. Thalidomide was well tolerated but caused variable degrees of sedation. The average thalidomide compliance rate was 97%. The pharmacokinetics of thalidomide do not change with 3 weeks of daily dosing. Thalidomide does not alter the pharmacokinetics of ethinyl estradiol or norethindrone. Therefore there is no drug interaction between thalidomide and these 2 drugs. The efficacy of oral contraceptives containing ethinyl estradiol and norethindrone should not be affected by concomitant thalidomide therapy.

  18. Estradiol Uptake in a Combined Magnetic Ion Exchange - Ultrafiltration (MIEX-UF) Process During Water Treatment.

    PubMed

    Imbrogno, Alessandra; Biscarat, Jennifer; Schafer, Andrea Iris

    2017-01-01

    Estrogens and their synthetic analogues are widely used as pharmaceuticals. Upon oral administration these drugs are eventually excreted via urine. The persistence of these pharmaceuticals and inefficient removal by water treatment lead to accumulation in surface water and effluents with negative effects for aquatic life and human health. In this study, the uptake of estradiol by a combined magnetic ion exchange resin - ultrafiltration process (MIEX-UF) was investigated. This is a relatively common process used in drinking water treatment for the removal of natural organic matter. However, uptake of micropollutants, such as steroidal pharmaceuticals, may occur as a side effect of water treatment due to the high affinity for polymeric materials. To elucidate the mechanism governing estradiol partitioning between water, resin and membrane, the influence of different parameters, such as pH, humic acid concentration and membrane molecular-weight-cut-off (MWCO) was studied. Humic acid concentration and pH affected estradiol uptake most. At pH 11 the most significant increase of estradiol uptake was observed for MIEX-UF process (30 ng/g corresponding to 80%) compared with individual UF (17 ng/g corresponding to 12%). The presence of humic acid slightly reduced estradiol uptake at pH 11 (about 55%) due to competition for the ion exchange binding sites. Results demonstrated that the uptake of estradiol, which is amongst the most potent EDCs detected in surface water, in the MIEX-UF process can reach significant quantities (30 ng/g of resin) leading to uncontrolled accumulation of this micropollutant during drinking water treatment. This study gives a novel contribution in the understanding the mechanism of the unanticipated accumulation of pharmaceuticals, such as estradiol, in the drinking water treatment process. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

    PubMed Central

    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.

    2014-01-01

    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. PMID:24878606

  20. Supplementation of Eurycoma longifolia Jack Extract for 6 Weeks Does Not Affect Urinary Testosterone: Epitestosterone Ratio, Liver and Renal Functions in Male Recreational Athletes

    PubMed Central

    Chen, Chee Keong; Mohamad, Wan Mohd Zahiruddin Wan; Ooi, Foong Kiew; Ismail, Shaiful Bahari; Abdullah, Mohamad Rusli; George, Annie

    2014-01-01

    Background: Eurycoma longifolia Jack (ElJ) has been shown to elevate serum testosterone and increased muscle strength in humans. This study investigated the effects of Physta® a standardized water extract of ElJ (400 mg/day for 6 weeks) on testosterone: epitestosterone (T:E) ratio, liver and renal functions in male recreational athletes. Methods: A total of 13 healthy male recreational athletes were recruited in this double blind, placebo-controlled, cross-over study. The participants were required to consume either 400 mg of ElJ or placebo daily for 6 weeks in the first supplementation regimen. Following a 3 week wash-out period, the participants were requested to consume the other supplement for another 6 weeks. Mid-stream urine samples and blood samples were collected prior to and after 6 weeks of supplementation with either ElJ or placebo. The urine samples were subsequently analyzed for T:E ratio while the blood samples were analyzed for liver and renal functions. Results: T:E ratio was not significantly different following 6 weeks supplementation of either ElJ or placebo compared with their respective baseline values. Similarly, there were no significant changes in both the liver and renal functions tests following the supplementation of ElJ. Conclusions: Supplementation of ElJ i.e. Physta® at a dosage of 400 mg/day for 6 weeks did not affect the urinary T:E ratio and hence will not breach any doping policies of the International Olympic Committee for administration of exogenous testosterone or its precursor. In addition, the supplementation of ElJ at this dosage and duration was safe as it did adversely affect the liver and renal functions. PMID:25013692

  1. Estradiol-sertraline synergy in ovariectomized rats.

    PubMed

    Sell, Stacy L; Craft, Rebecca M; Seitz, Patricia K; Stutz, Sonja J; Cunningham, Kathryn A; Thomas, Mary L

    2008-09-01

    This study investigated estradiol (E(2)) modulation of the antidepressant effects of a selective serotonin (5-HT) reuptake inhibitor (SSRI; sertraline) and a tricyclic antidepressant (imipramine) as measured by the forced swim test (FST) followed by assessment of gene and protein expression for the 5-HT transporter (SERT) and multiple 5-HT receptors. Female Sprague-Dawley rats were ovariectomized (OVX) and two-thirds of the rats received E(2) implants (OVE). 4 weeks later, implants were withdrawn in half of the OVE rats (OVW) to capture a time point when E(2) levels were rapidly declining. Rats in each hormone group were treated with vehicle, sertraline (10 mg/kg) or imipramine (10 mg/kg), 24, 5 and 1h before the FST. Immediately after the FST, midbrain, hippocampus and prefrontal cortex tissue was removed and frozen for analysis of gene expression via quantitative real-time PCR (midbrain tissue) and protein expression via Western blot (prefrontal cortex and hippocampal tissue). In the FST, sertraline decreased immobility and increased swimming in OVE rats, as well as increased swimming in OVW rats. In contrast, no sertraline effect was observed in OVX rats. Rats treated with imipramine showed increased climbing but no changes in immobility or swimming. No changes in protein expression were detected in any treatment group. However, in vehicle-treated rats, E(2) increased midbrain SERT mRNA expression, with no effect on midbrain mRNA for the 5-HT receptors. In sertraline-treated rats, E(2) decreased 5-HT(2A) receptor mRNA, and E(2)-withdrawal increased 5-HT(1A), 5-HT(2A) and 5-HT(2C) receptor mRNA. In imipramine-treated rats, E(2) (and E(2)-withdrawal) did not affect mRNA expression for any of the target genes. Thus, E(2) synergized behaviorally and neurochemically with an SSRI but not a tricyclic antidepressant.

  2. TGF-β1 pathway affects the protein expression of many signaling pathways, markers of liver cancer stem cells, cytokeratins, and TERT in liver cancer HepG2 cells.

    PubMed

    Wang, Xin-Hong; Liu, Ming-Na; Sun, Xun; Xu, Chun-Huan; Liu, Jing; Chen, Jing; Xu, Rui-Ling; Li, Bao-Xin

    2016-03-01

    Liver cancer is one of the most common human malignancies, and transforming growth factor-beta (TGF-β) pathway plays a key role in its pathogenesis. To study the relationship between TGF-β pathway and the related protein expression of many signaling pathway, markers of stem cells, CK family, and others, liver cancer HepG2 cells were transfected with siRNA directed against TGF-β1 or were treated with exogenous TGF-β1. Then, these protein levels were measured by Western blotting. After siRNA transfection, TGF-β1 protein level was decreased, indicating that the siRNA against it was effective. In exogenous TGF-β1 group, the expression of smad4, smad2/3, and β-catenin proteins was increased, whereas that of p-smad2/3, CD133, cleaved Notch1, and epithelial cell adhesion molecule (EpCAM) proteins at 48 h was decreased. The expression of CK8 and CK18 proteins was increased at 24 h and was decreased at 48 and 96 h. In TGF-β1-silenced group, the expression of smad2/3, β-catenin, cleaved-notch1, and CK18 proteins was decreased, while that of smad4, p-smad2/3, CD133, EpCAM, and CK8 proteins was increased. TERT protein expression was slightly increased in exogenous TGF-β1 group at 48 h and in TGF-β1-silenced group at 96 h. TGF-β1 did not affect the protein expression of CK19 and HIF-1. Thus, TGF-β1 pathway plays an important role in cell regulation of liver cancer through the modulation of these proteins. These data will contribute to the understanding of the pathogenesis of liver cancer and the role of TGF-β pathway in this process.

  3. Enantioselective S-oxygenation of para-methoxyphenyl-1,3-dithiolane by various tissue preparations: effect of estradiol.

    PubMed

    Cashman, J R; Olsen, L D; Lambert, C E; Presas, M J

    1990-02-01

    Liver, kidney, and lung microsomes prepared from nonpretreated female Sprague-Dawley rats catalyze the NADPH- and oxygen-dependent S-oxygenation of para-methoxyphenyl-1,3-dithiolane. Studies on the biochemical mechanism of dithiolane S-oxygenation in liver, kidney, and lung microsomes suggest that this reaction is catalyzed in a diastereoselective and enantioselective fashion by the flavin-containing monooxygenase and, to a lesser extent, the cytochromes P-450. This conclusion is based on results examining the effects of selective cytochrome P-450 inhibitors and positive effectors, microsome heat-inactivation treatment, and alternate substrates for the flavin-containing monooxygenase. Liver and kidney microsomes prepared from ovarectomized female rats tended to have decreased S-oxygenase activity, compared with nonpretreated female rats, whereas ovarectomized rats pretreated with estradiol had markedly lower S-oxygenase activity. In contrast, lung microsomal S-oxygenase activity, which is low in pulmonary microsomes from nonpretreated female rats, increases 2-4-fold after ovariectomization and estradiol pretreatment. In female Sprague-Dawley rats, estradiol pretreatment is mainly responsible for the large decrease (or increase) in S-oxygenase activity observed in the tissues examined, although it is unlikely that estradiol alone controls flavin-containing monooxygenase S-oxygenase activity.

  4. Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer

    PubMed Central

    2010-01-01

    Background Estrogens suppress tumor growth in prostate cancer which progresses despite anorchid serum androgen levels, termed castration resistant prostate cancers (CRPC), although the mechanisms are unclear. We hypothesize that estrogen inhibits CRPC in anorchid animals by suppressing tumoral androgens, an effect independent of the estrogen receptor. Methods The human CRPC xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo, 17β-estradiol or 17β-estradiol and estrogen receptor antagonist ICI 182,780. Effects of 17β-estradiol on tumor growth were evaluated and tissue testosterone (T) and dihydrotestosterone (DHT) evaluated by mass spectrometry. Results Treatment of LuCaP 35V with 17β-estradiol slowed tumor growth compared to controls (tumor volume at day 21: 785 ± 81 mm3 vs. 1195 ± 84 mm3, p = 0.002). Survival was also significantly improved in animals treated with 17β-estradiol (p = 0.03). The addition of the estrogen receptor antagonist ICI 182,780 did not significantly change survival or growth. 17β-estradiol in the presence and absence of ICI 182,780 suppressed tumor testosterone (T) and dihydrotestosterone (DHT) as assayed by mass spectrometry. Tissue androgens in placebo treated LuCaP 35V xenografts were; T = 0.71 ± 0.28 pg/mg and DHT = 1.73 ± 0.36 pg/mg. In 17β-estradiol treated LuCaP35V xenografts the tissue androgens were, T = 0.20 ± 0.10 pg/mg and DHT = 0.15 ± 0.15 pg/mg, (p < 0.001 vs. controls). Levels of T and DHT in control liver tissue were < 0.2 pg/mg. Conclusions CRPC in anorchid animals maintains tumoral androgen levels despite castration. 17β-estradiol significantly suppressed tumor T and DHT and inhibits growth of CRPC in an estrogen receptor independent manner. The ability to manipulate tumoral androgens will be critical in the development and testing of agents targeting CRPC through tissue steroidogenesis. PMID:20509933

  5. Redox regulation of protein tyrosine phosphatase 1B by manipulation of dietary selenium affects the triglyceride concentration in rat liver.

    PubMed

    Mueller, Andreas S; Klomann, Sandra D; Wolf, Nicole M; Schneider, Sandra; Schmidt, Rupert; Spielmann, Julia; Stangl, Gabriele; Eder, Klaus; Pallauf, Josef

    2008-12-01

    Protein tyrosine phosphatase 1B (PTP1B) is a key enzyme in the counter-regulation of insulin signaling and in the stimulation of fatty acid synthesis. Selenium (Se), via the activities of glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), is involved in the removal of H(2)O(2) and organic peroxides, which are critical compounds in the modulation of PTP1B activity via glutathionylation. Our study with growing rats investigated how the manipulation of dietary Se concentration influences the regulation of PTP1B and lipogenic effects mediated by PTP1B. Weanling albino rats were divided into 3 groups of 10. The negative control group (NC) was fed a Se-deficient diet for 8 wk. Rats in groups Se75 and Se150 received diets supplemented with 75 or 150 microg Se/kg. Se supplementation of the rats strongly influenced expression and activity of the selenoenzymes cytosolic GPx, plasma GPx, phospholipidhydroperoxide GPx, and cytosolic TrxR, and liver PTP1B. Liver PTP1B activity was significantly higher in groups Se75 and Se150 than in the NC group and this was attributed to a lowered inhibition of the enzyme by glutathionylation. The increased liver PTP1B activity in groups Se75 and Se150 resulted in 1.1- and 1.4-fold higher liver triglyceride concentrations than in the NC rats. The upregulation of the sterol regulatory element binding protein-1c and of fatty acid synthase, 2 PTP1B targets, provided a possible explanation for the lipogenic effect of PTP1B due to the manipulation of dietary Se. We therefore conclude that redox-regulated proteins, such as PTP1B, represent important interfaces between dietary antioxidants such as Se and the regulation of metabolic processes.

  6. Overexpression of Peroxiredoxin 4 Affects Intestinal Function in a Dietary Mouse Model of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Noguchi, Hirotsugu; Mazaki, Yuichi; Kurahashi, Toshihiro; Izumi, Hiroto; Wang, Ke-Yong; Guo, Xin; Uramoto, Hidetaka; Kohno, Kimitoshi; Taniguchi, Hatsumi; Tanaka, Yoshiya; Fujii, Junichi; Sasaguri, Yasuyuki; Tanimoto, Akihide; Nakayama, Toshiyuki

    2016-01-01

    Background Accumulating evidence has shown that methionine- and choline-deficient high fat (MCD+HF) diet induces the development of nonalcoholic fatty liver disease (NAFLD), in which elevated reactive oxygen species play a crucial role. We have reported that peroxiredoxin 4 (PRDX4), a unique secretory member of the PRDX antioxidant family, protects against NAFLD progression. However, the detailed mechanism and potential effects on the intestinal function still remain unclear. Methods & Results Two weeks after feeding mice a MCD+HF diet, the livers of human PRDX4 transgenic (Tg) mice exhibited significant suppression in the development of NAFLD compared with wild-type (WT) mice. The serum thiobarbituric acid reactive substances levels were significantly lower in Tg mice. In contrast, the Tg small intestine with PRDX4 overexpression showed more suppressed shortening of total length and villi height, and more accumulation of lipid in the jejunum, along with lower levels of dihydroethidium binding. The enterocytes exhibited fewer apoptotic but more proliferating cells, and inflammation was reduced in the mucosa. Furthermore, the small intestine of Tg mice had significantly higher expression of cholesterol absorption-regulatory factors, including liver X receptor-α, but lower expression of microsomal triglyceride-transfer protein. Conclusion Our present data provide the first evidence of the beneficial effects of PRDX4 on intestinal function in the reduction of the severity of NAFLD, by ameliorating oxidative stress-induced local and systemic injury. We can suggest that both liver and intestine are spared, to some degree, by the antioxidant properties of PRDX4. PMID:27035833

  7. Muscle or liver-specific Sirt3 deficiency induces hyperacetylation of mitochondrial proteins without affecting global metabolic homeostasis

    PubMed Central

    Fernandez-Marcos, Pablo J.; Jeninga, Ellen H.; Canto, Carles; Harach, Taoufiq; de Boer, Vincent C. J.; Andreux, Penelope; Moullan, Norman; Pirinen, Eija; Yamamoto, Hiroyasu; Houten, Sander M.; Schoonjans, Kristina; Auwerx, Johan

    2012-01-01

    Sirt3 is a mitochondrial sirtuin, predominantly expressed in highly metabolic tissues. Germline ablation of Sirt3 has major metabolic consequences, including increased susceptibility to metabolic damage and oxidative stress after high fat feeding. In order to determine the contribution of liver and skeletal muscle to these phenotypes, we generated muscle-specific Sirt3 (Sirt3skm−/−) and liver-specific Sirt3 (Sirt3hep−/−) knock-out mice. Despite a marked global hyperacetylation of mitochondrial proteins, Sirt3skm−/− and Sirt3hep−/− mice did not manifest any overt metabolic phenotype under either chow or high fat diet conditions. Similarly, there was no evidence for increased oxidative stress in muscle or liver when Sirt3 was ablated in a tissue-specific manner. These observations suggest that the mitochondrial hyperacetylation induced by Sirt3-deletion in a tissue specific manner is not necessarily linked to mitochondrial dysfunction and does not recapitulate the metabolic abnormalities observed in the germline Sirt3 knock-out mice. PMID:22645641

  8. Prolonged, but transient, elevation of liver and biliary function tests in a healthy infant affected with breast milk jaundice.

    PubMed

    Poddighe, Dimitri; Castelli, Lucia; Marseglia, Gian Luigi; Bruni, Paola

    2014-05-28

    Unconjugated hyperbilirubinaemia is a common finding in newborns. When it is exaggerated, it is usually investigated in order to exclude several diseases, such as newborn's haemolytic diseases, infections or hypothyroidism. Breast milk jaundice is a form of neonatal jaundice related to breast feeding and it is not usually associated with any clinical issue and/or other laboratory abnormalities. We describe a case of breast milk jaundice being associated, unexpectedly, to significant elevation of plasmatic liver and biliary enzymes. Despite the infant's good clinical condition and growth, several investigations were performed and these ruled out metabolic, infectious and autoimmune liver diseases. All liver function tests normalised by 6-7 months of life. We suggest that the finding of hypertransaminasaemia and hyper-γ-glutamyl transpeptidase in a benign clinical context (similar to what we described) should be followed for 6-7 months before performing sophisticated and expensive diagnostic investigations which aim at excluding some unlikely and severe diseases in a completely asymptomatic infant.

  9. Muscle or liver-specific Sirt3 deficiency induces hyperacetylation of mitochondrial proteins without affecting global metabolic homeostasis.

    PubMed

    Fernandez-Marcos, Pablo J; Jeninga, Ellen H; Canto, Carles; Harach, Taoufiq; de Boer, Vincent C J; Andreux, Penelope; Moullan, Norman; Pirinen, Eija; Yamamoto, Hiroyasu; Houten, Sander M; Schoonjans, Kristina; Auwerx, Johan

    2012-01-01

    Sirt3 is a mitochondrial sirtuin, predominantly expressed in highly metabolic tissues. Germline ablation of Sirt3 has major metabolic consequences, including increased susceptibility to metabolic damage and oxidative stress after high fat feeding. In order to determine the contribution of liver and skeletal muscle to these phenotypes, we generated muscle-specific Sirt3 (Sirt3(skm-/-)) and liver-specific Sirt3 (Sirt3(hep-/-)) knock-out mice. Despite a marked global hyperacetylation of mitochondrial proteins, Sirt3(skm-/-) and Sirt3(hep-/-) mice did not manifest any overt metabolic phenotype under either chow or high fat diet conditions. Similarly, there was no evidence for increased oxidative stress in muscle or liver when Sirt3 was ablated in a tissue-specific manner. These observations suggest that the mitochondrial hyperacetylation induced by Sirt3-deletion in a tissue specific manner is not necessarily linked to mitochondrial dysfunction and does not recapitulate the metabolic abnormalities observed in the germline Sirt3 knock-out mice.

  10. Copper and endogenous mediators of estradiol action.

    PubMed

    Fishman, J H; Fishman, J

    1988-04-29

    Divalent copper increases by severalfold specific estradiol binding in rat uterine cytosol at 37 degrees C. Two endogenous substances have now been isolated from the cytosol one of which sharply inhibits the copper effect while the other sharply promotes it. The inhibitor is thermostable, it is adsorbed by dextran coated charcoal and elutes from Sephadex columns with water. The promoter is thermolabile at 60 degrees C, it is not readily adsorbed by the charcoal and elutes from Sephadex columns with KCl. The two substances are thought to be mediators of estradiol action.

  11. Bisphenol A and estradiol are equipotent in antagonizing cisplatin-induced cytotoxicity in breast cancer cells.

    PubMed

    LaPensee, Elizabeth W; LaPensee, Christopher R; Fox, Sejal; Schwemberger, Sandy; Afton, Scott; Ben-Jonathan, Nira

    2010-04-28

    Resistance to chemotherapy is a major problem facing breast cancer patients. Cisplatin, a highly effective DNA-damaging drug, has shown only little success in breast cancer treatment. We are reporting that low nanomolar doses of bisphenol A (BPA) or estradiol antagonize cisplatin cytotoxicity in breast cancer cells, with their effects not mediated via classical estrogen receptors. Although both compounds increase the expression of Bcl-2, a Bcl-2 inhibitor completely blocked the protective effects of BPA while only partially affecting those of estradiol. Blockade of BPA and E2 actions should sensitize ER-negative breast tumors to anti-cancer drugs and allow for the inclusion of cisplatin in treatment regimens.

  12. 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.

  13. The effects of estradiol on mood and behavior in human female adolescents: a systematic review.

    PubMed

    Balzer, Ben W R; Duke, Sally-Anne; Hawke, Catherine I; Steinbeck, Katharine S

    2015-03-01

    Mood disorders and health risk behaviors increase in adolescence. Puberty is considered to contribute to these events. However, the precise impact of pubertal hormone changes to the emergence of mood disorders and risk behaviors is relatively unclear. It is important that inappropriate attribution is not made. Our aim was to determine what is known about the effect of endogenous estradiol on human adolescent girls' mood and behavior. The databases searched were MEDLINE, Embase, PsycINFO, Education Resources Information Center (ERIC), Pre-MEDLINE, Web of Science, and Scopus for all dates to October 2014. For inclusion, contemporaneous hormone and mood or behavioral assessment was required. Data were extracted following a template created by the authors. Fourteen studies met our inclusion criteria. There was some consistency in findings for mood and estradiol levels, with associations between estradiol and depression and emotional tone and risk taking. Results were less consistent for studies assessing other mood and behavioral outcomes. Most studies were cross-sectional in design; assay methodologies used in older studies may lack the precision to detect early pubertal hormone levels. Three longitudinal and several cross-sectional studies indicate potential associations between estradiol and certain mood or affective states, especially depression and mood variability though there are insufficient data to confirm that the rise in estradiol during puberty is causative. We believe that it is important for health professionals to take care when attributing adolescent psychopathology to puberty hormones, as the current data supporting these assertions are limited.

  14. Effects of Elevated β-Estradiol Levels on the Functional Morphology of the Testis - New Insights

    PubMed Central

    Leavy, Myles; Trottmann, Matthias; Liedl, Bernhard; Reese, Sven; Stief, Christian; Freitag, Benjamin; Baugh, John; Spagnoli, Giulio; Kölle, Sabine

    2017-01-01

    Elevated estradiol levels are correlated with male infertility. Causes of hyperestrogenism include diseases of the adrenal cortex, testis or medications affecting the hypothalamus-pituitary-gonadal axis. The aim of our study was to elucidate the effects of estradiol treatment on testicular cellular morphology and function, with reference to the treatment regimen received. Testes samples (n = 9) were obtained post-orchiectomy from male-to-female transsexuals within the age range of 26–52 years. Each patient had a minimum of 1–6 years estradiol treatment. For comparison, additional samples were obtained from microscopically unaltered testicular tissue surrounding tumors (n = 7). The tissues obtained were investigated by stereomicroscopy, histochemistry, scanning electron microscopy (SEM) and immunohistochemistry. Our studies revealed that estradiol treatment significantly decreased the diameter of the seminiferous tubules (p < 0.05) and induced fatty degeneration in the surrounding connective tissue. An increase in collagen fiber synthesis in the extracellular matrix (ECM) surrounding the seminiferous tubules was also induced. Spermatogenesis was impaired resulting in mainly spermatogonia being present. Sertoli cells revealed diminished expression of estrogen receptor alpha (ERα). Both Sertoli and Leydig cells showed morphological alterations and glycoprotein accumulations. These results demonstrate that increased estradiol levels drastically impact the human testis. PMID:28045098

  15. Estradiol and raloxifene protect cultured SN4741 neurons against oxidative stress.

    PubMed

    Biewenga, Eric; Cabell, Leigh; Audesirk, Teresa

    2005-01-20

    A large body of research has documented neuroprotective effects of estrogen against oxidative stress. Some neurodegenerative diseases such as Parkinson's disease, in which oxidative stress has been implicated as a contributing factor, affect more males than females, suggesting a possible protective effect of estrogen. We used the clonal substantia nigra cell line SN4741 to compare the neuroprotective properties of estrogen and raloxifene against oxidative stress, and to determine whether raloxifene acted as an estrogen agonist or antagonist in this system. We pretreated SN4741 cultures with alpha-estradiol, beta-estradiol, and raloxifene, and exposed them to hydrogen peroxide. Low nanomolar levels of raloxifene, beta-estradiol, and alpha-estradiol all significantly reduced cell death caused by oxidative stress. The estrogen receptor (ER) antagonist ICI 182,780 failed to reverse the neuroprotection by beta-estradiol, suggesting that the effect is not mediated by a classical ER. Western blotting using an antibody to the C-terminus region of ER-alpha revealed two bands, one at approximately 67 kDa (corresponding to ER-alpha) and a more prominent band at approximately 55-56 kDa. These results suggest that, in this cell line, both raloxifene and estrogen may be acting via a non-classical estrogen receptor.

  16. Gene expression profile regulated by the HPV16 E7 oncoprotein and estradiol in cervical tissue

    PubMed Central

    Cortés-Malagón, Enoc M.; Bonilla-Delgado, José; Díaz-Chávez, José; Hidalgo-Miranda, Alfredo; Romero-Cordoba, Sandra; Üren, Aykut; Çelik, Haydar; McCormick, Matthew; Munguía-Moreno, José A.; Ibarra-Sierra, Eloisa; Escobar-Herrera, Jaime; Lambert, Paul F.; Mendoza-Villanueva, Daniel; Bermudez-Cruz, Rosa M.; Gariglio, Patricio

    2014-01-01

    The HPV16 E7 oncoprotein and 17β-estradiol are important factors for the induction of premalignant lesions and cervical cancer. The study of these factors is crucial for a better understanding of cervical tumorigenesis. Here, we assessed the global gene expression profiles induced by the HPV16 E7 oncoprotein and/or 17β-estradiol in cervical tissue of FvB and K14E7 transgenic mice. We found that the most dramatic changes in gene expression occurred in K14E7 and FvB groups treated with 17β-estradiol. A large number of differentially expressed genes involved in the immune response were observed in 17β-estradiol treated groups. The E7 oncoprotein mainly affected the expression of genes involved in cellular metabolism. Our microarray data also identified differentially expressed genes that have not previously been reported in cervical cancer. The identification of genes regulated by E7 and 17β-estradiol, provides the basis for further studies on their role in cervical carcinogenesis. PMID:24210110

  17. Estradiol regulates expression of miRNAs associated with myogenesis in rainbow trout

    USDA-ARS?s Scientific Manuscript database

    17-Estradiol (E2) is a steroid hormone that negatively affects muscle growth in rainbow trout, but the mechanism associated with this response is not fully understood. To better characterize the effects of E2 on muscle, we identified differentially regulated microRNAs (miRNAs) and muscle atrophy-rel...

  18. Pregnancy rates after ewes were treated with estradiol-17beta and oxytocin.

    USDA-ARS?s Scientific Manuscript database

    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...

  19. 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…

  20. 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…

  1. Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure.

    PubMed

    Li, Han-Min; Ye, Zhi-Hua; Zhang, Jun; Gao, Xiang; Chen, Yan-Ming; Yao, Xin; Gu, Jian-Xun; Zhan, Lei; Ji, Yang; Xu, Jian-Liang; Zeng, Ying-He; Yang, Fan; Xiao, Lin; Sheng, Guo-Guang; Xin, Wei; Long, Qi; Zhu, Qing-Jing; Shi, Zhao-Hong; Ruan, Lian-Guo; Yang, Jia-Yao; Li, Chang-Chun; Wu, Hong-Bin; Chen, Sheng-Duo; Luo, Xin-La

    2014-12-28

    To study the clinical efficacy of traditional Chinese medicine (TCM) intervention "tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment" ("TTK") for treating liver failure due to chronic hepatitis B. We designed the study as a randomized controlled clinical trial. Registration number of Chinese Clinical Trial Registry is ChiCTR-TRC-12002961. A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study. Participants were randomly assigned to the following three groups: (1) a modern medicine control group (MMC group, 36 patients); (2) a "tonifying qi and detoxification" ("TQD") group (72 patients); and (3) a "tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment" ("TTK") group (36 patients). Patients in the MMC group received general internal medicine treatment; patients in the "TQD" group were given a TCM formula "tonifying qi and detoxification" and general internal medicine treatment; patients in the "TTK" group were given a TCM formula of "TTK" and general internal medicine treatment. All participants were treated for 8 wk and then followed at 48 wk following their final treatment. The primary efficacy end point was the patient fatality rate in each group. Measurements of various virological and biochemical indicators served as secondary endpoints. The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups. At the 48-wk post-treatment time point, the patient fatality rates in the MMC, "TQD", and "TTK" groups were 51.61%, 35.38%, and 16.67%, respectively, and the differences between groups were statistically significant (P < 0.05). However, there were no significant differences in the levels of hepatitis B virus DNA or prothrombin activity among the three groups (P > 0.05). Patients in the "TTK

  2. Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure

    PubMed Central

    Li, Han-Min; Ye, Zhi-Hua; Zhang, Jun; Gao, Xiang; Chen, Yan-Ming; Yao, Xin; Gu, Jian-Xun; Zhan, Lei; Ji, Yang; Xu, Jian-Liang; Zeng, Ying-He; Yang, Fan; Xiao, Lin; Sheng, Guo-Guang; Xin, Wei; Long, Qi; Zhu, Qing-Jing; Shi, Zhao-Hong; Ruan, Lian-Guo; Yang, Jia-Yao; Li, Chang-Chun; Wu, Hong-Bin; Chen, Sheng-Duo; Luo, Xin-La

    2014-01-01

    AIM: To study the clinical efficacy of traditional Chinese medicine (TCM) intervention “tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment” (“TTK”) for treating liver failure due to chronic hepatitis B. METHODS: We designed the study as a randomized controlled clinical trial. Registration number of Chinese Clinical Trial Registry is ChiCTR-TRC-12002961. A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study. Participants were randomly assigned to the following three groups: (1) a modern medicine control group (MMC group, 36 patients); (2) a “tonifying qi and detoxification” (“TQD”) group (72 patients); and (3) a “tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment” (“TTK”) group (36 patients). Patients in the MMC group received general internal medicine treatment; patients in the “TQD” group were given a TCM formula “tonifying qi and detoxification” and general internal medicine treatment; patients in the “TTK” group were given a TCM formula of “TTK” and general internal medicine treatment. All participants were treated for 8 wk and then followed at 48 wk following their final treatment. The primary efficacy end point was the patient fatality rate in each group. Measurements of various virological and biochemical indicators served as secondary endpoints. The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups. RESULTS: At the 48-wk post-treatment time point, the patient fatality rates in the MMC, “TQD”, and “TTK” groups were 51.61%, 35.38%, and 16.67%, respectively, and the differences between groups were statistically significant (P < 0.05). However, there were no significant differences in the levels of hepatitis B virus DNA or prothrombin

  3. Influence of nicotine on progesterone and estradiol production of cultured human granulosa cells.

    PubMed

    Bódis, J; Hanf, V; Török, A; Tinneberg, H R; Borsay, P; Szabó, I

    1997-03-01

    The purpose of this study was to investigate the direct action of one of the main constituents of cigarette smoke on corpus luteum function. Progesterone and estradiol production were measured in the presence and absence of nicotine as free base or bitartrate salt with or without luteinizing hormone (LH) stimulation using radioimmunoassay in an in vitro granulosa cell culture system. Human granulosa cells were obtained from 19 patients undergoing in vitro fertilization embryo transfer treatment for infertility at the University Women's Hospital, Tübinge, Germany. Nicotine free base augmented estradiol secretion and inhibited progesterone secretion by human granulosa cells in a dose-dependent manner. Nicotine bitartrate had little effect on steroid secretion. If granulosa cells were stimulated with LH, both nicotine preparations suppressed estradiol secretion, however, only nicotine bitartrate additionally inhibited progesterone secretion. The results suggest that cigarette smoking specifically affects the control mechanisms of intraovarian processes which are responsible for normal luteal function.

  4. Cadmium affects the mitochondrial viability and the acid soluble thiols concentration in liver, kidney, heart and gills of Ancistrus brevifilis (Eigenmann, 1920)

    PubMed Central

    Velasquez-Vottelerd, P.; Anton, Y.; Salazar-Lugo, R.

    2015-01-01

    The freshwater fish Ancistrus brevifilis, which is found in Venezuelan rivers, is considered a potential sentinel fish in ecotoxicological studies. The cadmium (Cd) effect on the mitochondrial viability (MV) and acid soluble thiols levels (AST) in A. brevifilis tissues (liver, kidney, heart, and gill) was evaluated. Forty-two fish with similar sizes and weights were randomly selected, of which 7 fish (with their respective replicate) were exposed for 7 and 30 days to a Cd sublethal concentration (0.1 mg.l-1). We determined the MV through a Janus Green B colorimetric assay and we obtained the concentration of AST by Ellman’s method. Mitochondrial viability decreased in fish exposed to Cd for 30 days with the liver being the most affected tissue. We also detected a significant decrease in AST levels was in fishes exposed to Cd for 7 days in liver and kidney tissues; these results suggests that AST levels are elevated in some tissues may act as cytoprotective and adaptive alternative mechanism related to the ROS detoxification, maintenance redox status and mitochondrial viability. Organ-specifics variations were observed in both assays. We conclude that the Cd exposure effect on AST levels and MV, vary across fish tissues and is related to the exposure duration, the molecule dynamics in different tissues, the organism and environmental conditions. PMID:26623384

  5. Estradiol-induced alopecia in five dogs after contact with a transdermal gel used for the treatment of postmenopausal symptoms in women.

    PubMed

    Wiener, Dominique J; Rüfenacht, Silvia; Koch, Hans J; Mauldin, Elizabeth A; Mayer, Ursula; Welle, Monika M

    2015-10-01

    Noninflammatory alopecia is a frequent problem in dogs. Estrogen-induced alopecia is well described in dogs, with estrogen producing testicular tumors and canine female hyperestrogenism. To increase awareness that extensive alopecia in dogs can be caused by exposure to estradiol gel used by owners to treat their postmenopausal symptoms. Skin biopsies from five dogs with extensive alopecia were examined. Owners were asked for a thorough case history, including possible exposure to an estradiol gel. Complete blood work and serum chemistry panel analysis were performed to investigate possible underlying causes. Formalin-fixed skin biopsy samples were obtained from lesional skin and histopathology was performed. All owners confirmed the use of a transdermal estradiol gel and close contact with the affected dogs before development of alopecia. Histopathologic examination showed a similar picture in all five dogs. Most hair follicles were predominantly either in kenogen or telogen and hair follicle infundibula showed mild to moderate dilation. Hair regrowth was present in all five dogs after the exposure to the estradiol gel was stopped or minimized. Blood work and serum chemistry panel were within normal limits in all cases. One dog had elevated estradiol concentrations, whereas in another dog estradiol concentrations were within normal limits. Alopecia can occur after contact with a transdermal gel used as treatment for postmenopausal symptoms in women. Estradiol gel used by female owners therefore represents a possible cause for noninflammatory alopecia in dogs. Estradiol concentrations are not necessarily elevated in affected dogs. © 2015 ESVD and ACVD.

  6. 21 CFR 556.240 - Estradiol and related esters.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol... increments above the concentrations of estradiol naturally present in untreated animals: (a) In uncooked...

  7. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  8. 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... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  10. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  11. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  12. 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,…

  13. 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,…

  14. 21 CFR 522.2477 - Trenbolone acetate and estradiol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... milligrams (mg) trenbolone acetate and 24 mg estradiol (one implant consisting of 6 pellets, each pellet containing 20 mg trenbolone acetate and 4 mg estradiol) per implant dose. (B) 120 mg trenbolone acetate and 24 mg estradiol (one implant consisting of 7 pellets, each of 6 pellets containing 20 mg...

  15. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...: (1) Suckling beef calves—(i) Amount—(A) 100 milligrams (mg) progesterone and 10 mg estradiol benzoate (one implant consisting of 4 pellets, each pellet containing 25 mg progesterone and 2.5 mg estradiol benzoate) per implant dose. (B) 100 mg progesterone and 10 mg estradiol benzoate (one implant consisting...

  16. 21 CFR 522.2477 - Trenbolone acetate and estradiol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... milligrams (mg) trenbolone acetate and 24 mg estradiol (one implant consisting of 6 pellets, each pellet containing 20 mg trenbolone acetate and 4 mg estradiol) per implant dose. (B) 120 mg trenbolone acetate and 24 mg estradiol (one implant consisting of 7 pellets, each of 6 pellets containing 20 mg...

  17. 3,5,3′-Triiodo-L-Thyronine- and 3,5-Diiodo-L-Thyronine- Affected Metabolic Pathways in Liver of LDL Receptor Deficient Mice

    PubMed Central

    Moreno, Maria; Silvestri, Elena; Coppola, Maria; Goldberg, Ira J.; Huang, Li-Shin; Salzano, Anna M.; D'Angelo, Fulvio; Ehrenkranz, Joel R.; Goglia, Fernando

    2016-01-01

    3,5,3′-triiodo-L-thyronine (T3) and 3,5-diiodo-L-thyronine (T2), when administered to a model of familial hypercholesterolemia, i.e., low density lipoprotein receptor (LDLr)-knockout (Ldlr−/−) mice fed with a Western type diet (WTD), dramatically reduce circulating total and very low-density lipoprotein/LDL cholesterol with decreased liver apolipoprotein B (ApoB) production. The aim of the study was to highlight putative molecular mechanisms to manage cholesterol levels in the absence of LDLr. A comprehensive comparative profiling of changes in expression of soluble proteins in livers from Ldlr−/− mice treated with either T3 or T2 was performed. From a total proteome of 450 liver proteins, 25 identified proteins were affected by both T2 and T3, 18 only by T3 and 9 only by T2. Using in silico analyses, an overlap was observed with 11/14 pathways common to both iodothyronines, with T2 and T3 preferentially altering sub-networks centered around hepatocyte nuclear factor 4 α (HNF4α) and peroxisome proliferator-activated receptor α (PPARα), respectively. Both T2 and T3 administration significantly reduced nuclear HNF4α protein content, while T2, but not T3, decreased the expression levels of the HNFα transcriptional coactivator PGC-1α. Lower PPARα levels were found only following T3 treatment while both T3 and T2 lowered liver X receptor α (LXRα) nuclear content. Overall, this study, although it was not meant to investigate the use of T2 and T3 as a therapeutic agent, provides novel insights into the regulation of hepatic metabolic pathways involved in T3- and T2-driven cholesterol reduction in Ldlr−/− mice. PMID:27909409

  18. ELEVATION OF SERUM 17-B-ESTRADIOL IN CHANNEL CATFISH FOLLOWING INJECTION OF 17-B-ESTRADIOL, ETHYNYL ESTRADIOL, ESTRONE, ESTRIOL, AND ESTRADIOL-17B- GLUCURONIDE

    EPA Science Inventory

    17-b-Estradiol is naturally converted in numerous organisms to various derivatives/metabolites, which may be excreted from the organism into its immediate external environment. There is a paucity of data regarding the biological effects of the derivatives/metabolites on aquatic o...

  19. Liver Transplant

    MedlinePlus

    ... Home > Your Liver > Liver Disease Information > Liver Transplant Liver Transplant Explore this section to learn more about ... resource. www.paulcox.com.au Why is the liver important? The liver is the second largest organ ...

  20. Coffee consumption could affect the activity of some liver enzymes and other biochemical parameters in healthy drinkers.

    PubMed

    Onuegbu, Anaelechi J; Olisekodiaka, Japhet M; Adebolu, Olubukunmi E; Adesiyan, Adekunle; Ayodele, Olugbenga E

    2011-01-01

    To investigate the effect of coffee consumption on some liver function indices in adult male and female Nigerians. Thirty apparently healthy subjects, consisting of 18 men and 12 women, were made to consume 2 g of coffee daily for a total of 30 days. Activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and plasma concentrations of total and conjugated bilirubin, total protein and albumin were determined using standard methods. Relative to baseline values, coffee consumption raised mean levels of ALT by 4 IU/l (p < 0.001), AST by 2.0 1 U/l (p < 0.001), ALP by 3.0 1 U/l (p < 0.01), total bilirubin by 0.90 mg/dl (p < 0.05) and total protein by 1.1 g/l (p < 0.05). Gender differences were observed. Significantly higher mean ALP concentration was only seen in male subjects, while mean bilirubin concentration was significantly raised in female volunteers alone. On the other hand, the mean total protein and albumin concentrations in individual male and female groups were not significantly altered (p > 0.05 in each case). The result obtained from the study suggests that short-term consumption of coffee might have a significant effect on the integrity of the liver function tests studied. Copyright © 2011 S. Karger AG, Basel.

  1. Donation After Circulatory Death for Liver Transplantation: A Meta-Analysis on the Location of Life Support Withdrawal Affecting Outcomes.

    PubMed

    Cao, Yiming; Shahrestani, Sara; Chew, Hong Chee; Crawford, Michael; Macdonald, Peter Simon; Laurence, Jerome; Hawthorne, Wayne John; Dhital, Kumud; Pleass, Henry

    2016-07-01

    Liver transplantation using donation after circulatory death (DCD) donors is associated with inferior outcomes compared to donation after brain death (DBD). Prolonged donor warm ischemic time has been identified as the key factor responsible for this difference. Various aspects of the donor life support withdrawal procedure, including location of withdrawal and administration of antemortem heparin, are thought to play important roles in mitigating the effects of warm ischemia. However, a systematic exploration of these factors is important for more confident integration of these practices into a standard DCD protocol. Medline, EMBASE, and Cochrane libraries were systematically searched and 23 relevant studies identified for analysis. Donation after circulatory death recipients were stratified according to location of life support withdrawal (intensive care unit or operating theater) and use of antemortem heparin. Donation after circulatory death recipients had comparable 1-year patient survival to DBD recipients if the location of withdrawal of life support was the operating theater, but not if the location was the intensive care unit. Likewise, the inferior 1-year graft survival and higher incidence of ischemic cholangiopathy of DCD compared with DBD recipients were improved by withdrawal in operating theater, although higher rates of ischemic cholangiopathy and worse graft survival were still observed in DCD recipients. Furthermore, administering heparin before withdrawal of life support reduced the incidence of primary nonfunction of the allograft. Our evidence suggests that withdrawal in the operating theater and premortem heparin administration improve DCD liver transplant outcomes, thus allowing for the most effective usage of these valuable organs.

  2. Metabolically active extracellular vesicles released from hepatocytes under drug-induced liver-damaging conditions modify serum metabolome and might affect different pathophysiological processes.

    PubMed

    Royo, Felix; Palomo, Laura; Mleczko, Justyna; Gonzalez, Esperanza; Alonso, Cristina; Martínez, Ibon; Pérez-Cormenzana, Miriam; Castro, Azucena; Falcon-Perez, Juan M

    2017-02-15

    Hepatocytes are involved in the endogenous and drug metabolism; many of the enzymes involved in those processes are incorporated into extracellular vesicles and secreted into the bloodstream. Liver-damaging conditions modify the molecular cargo of those vesicles significantly. However, no information about the effect of these hepatic vesicles on the extracellular environment is available. Drug-induced liver damage increases the number of circulating extracellular vesicles and affects the release and content of hepatocyte-derived vesicles. In this work, we evaluated the metabolic effect of these vesicles on the composition of the serum. We performed a targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) metabolomics analysis of serum samples. The samples had been first incubated with hepatic extracellular vesicles from hepatocytes challenged with acetaminophen or diclofenac. The incubation affected the serum levels of 67 metabolites, such as amino acids and different species of lipids. The metabolites included various species of phosphatidylcholines and phosphatidylethanolamines. These compounds are the components of biological membranes; our observations suggest that the vesicles might take part in remodelling and maintenance of the membranes. Alterations in the levels of some other serum metabolites might have deleterious consequences, for example, the tetracosanoic acid with its cardiovascular effects. However, some of the metabolites whose levels were increased, including alpha-linoleic and tauroursodeoxycholic acids, have been reported to have a protective effect. Our targeted metabolomics analysis indicated that the hepatic extracellular vesicles act as nano-metabolic machines supplying the extracellular environment with the means to integrate diverse tissue responses. In conclusion, we show that the hepatic extracellular vesicles are metabolically active and might play a role in the physiopathological response to hepatic insults

  3. Liver disease in menopause.

    PubMed

    Brady, Carla W

    2015-07-07

    There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure.

  4. The organizational and aromatization hypotheses apply to rapid, nonclassical hormone action: neonatal masculinization eliminates rapid estradiol action in female hippocampal neurons.

    PubMed

    Meitzen, John; Grove, Danielle D; Mermelstein, Paul G

    2012-10-01

    Early exposure to the steroid sex hormone testosterone and its estrogen metabolite estradiol masculinize neural tissue during a developmental critical period. Many aspects of neuron anatomy and physiology are permanently altered, including later sensitivity to estradiol. Although it is well established that early hormone exposure alters neuronal responsiveness regarding classical estradiol actions (i.e. acting via nuclear estrogen receptors), it has not yet been determined whether it also alters neuronal processing of nonclassical estrogen receptor signaling, including the actions of membrane-associated estrogen receptors. Hence, we tested whether membrane estrogen receptor regulation of cAMP response element binding protein (CREB) phosphorylation observed in female (but not male) hippocampal pyramidal neurons is due to the lack of androgen and/or estrogen exposure in females during this critical period. Female rat neonates on postnatal d 0 and 1 were systemically injected with one of four compounds: vehicle, testosterone, the nonaromatizable androgen dihydrotestosterone, or estradiol. On postnatal d 2, primary hippocampal neuron cultures were generated from these animals. After 8-9 d in culture, we assessed whether estradiol affected CREB phosphorylation. Neurons from female neonates exposed to testosterone lacked estradiol signaling to CREB. In contrast, dihydrotestosterone injections of female neonates did not disrupt estradiol regulation of CREB. Estradiol injections of female neonates, however, eliminated estradiol signaling to CREB. These findings indicate that testosterone aromatization to estradiol leads to a masculinization/defeminization process whereby hippocampal neurons fail to exhibit rapid estradiol signaling to CREB. Broadly, these findings extend the organizational and aromatization hypotheses to rapid, nonclassical hormone action.

  5. The Organizational and Aromatization Hypotheses Apply to Rapid, Nonclassical Hormone Action: Neonatal Masculinization Eliminates Rapid Estradiol Action in Female Hippocampal Neurons

    PubMed Central

    Grove, Danielle D.; Mermelstein, Paul G.

    2012-01-01

    Early exposure to the steroid sex hormone testosterone and its estrogen metabolite estradiol masculinize neural tissue during a developmental critical period. Many aspects of neuron anatomy and physiology are permanently altered, including later sensitivity to estradiol. Although it is well established that early hormone exposure alters neuronal responsiveness regarding classical estradiol actions (i.e. acting via nuclear estrogen receptors), it has not yet been determined whether it also alters neuronal processing of nonclassical estrogen receptor signaling, including the actions of membrane-associated estrogen receptors. Hence, we tested whether membrane estrogen receptor regulation of cAMP response element binding protein (CREB) phosphorylation observed in female (but not male) hippocampal pyramidal neurons is due to the lack of androgen and/or estrogen exposure in females during this critical period. Female rat neonates on postnatal d 0 and 1 were systemically injected with one of four compounds: vehicle, testosterone, the nonaromatizable androgen dihydrotestosterone, or estradiol. On postnatal d 2, primary hippocampal neuron cultures were generated from these animals. After 8–9 d in culture, we assessed whether estradiol affected CREB phosphorylation. Neurons from female neonates exposed to testosterone lacked estradiol signaling to CREB. In contrast, dihydrotestosterone injections of female neonates did not disrupt estradiol regulation of CREB. Estradiol injections of female neonates, however, eliminated estradiol signaling to CREB. These findings indicate that testosterone aromatization to estradiol leads to a masculinization/defeminization process whereby hippocampal neurons fail to exhibit rapid estradiol signaling to CREB. Broadly, these findings extend the organizational and aromatization hypotheses to rapid, nonclassical hormone action. PMID:22865367

  6. Fathead minnow and bluegill sunfish life-stage responses to 17β-estradiol exposure in outdoor mesocosms

    USGS Publications Warehouse

    Elliott, Sarah M.; Kiesling, Richard L.; Jorgenson, Zachary G.; Rearick, Daniel C.; Schoenfuss, Heiko L.; Fredricks, Kim T.; Gaikowski, Mark P.

    2014-01-01

    Developmental and reproductive effects of 17β-estradiol (E2) exposure on two generations of fathead minnows and one generation of bluegill sunfish were assessed. Fish were exposed to E2 for six continuous weeks in outdoor mesocosms simulating natural lake environments. First generation fish were exposed while sexually mature. Second generation fathead minnows were exposed either during early development, sexual maturity, or both stages. Multiple endpoints were measured to assess effects of E2 exposure on fecundity and fish health and development. Plasma vitellogenin concentrations were highly variable in all fish. Differences in egg production timing for both species indicate differences in fecundity between females exposed to E2 and controls. First generation fathead minnows exposed to E2 had lower body condition factors and reduced secondary sexual characteristic expression by males. Only a difference in relative liver weight was observed in second generation fathead minnows. First generation bluegill males exposed to E2 had significantly smaller testes compared to controls. Although fish response was highly variable, results indicate that exposure to E2 at environmentally relevant concentrations affect fathead minnow and bluegill sunfish health and development, which may have implications for the health and sustainability of fish populations. Furthermore, exposure timing and environmental factors affect fish response to E2 exposure.

  7. Source of metabolizable energy affects gene transcription in metabolic pathways in adipose and liver tissue of nonlactating, pregnant dairy cows.

    PubMed

    Crookenden, M A; Mandok, K S; Grala, T M; Phyn, C V C; Kay, J K; Greenwood, S L; Roche, J R

    2015-02-01

    The objective of this experiment was to determine if transcript abundance of genes involved in metabolic pathways in adipose and liver tissue could provide some explanation for the low efficiency with which ME in autumn pasture is used for BW gain. Nonlactating, pregnant (208 ± 19 d of gestation or approximately 75 d precalving) dairy cows (n = 90) were randomly allocated to either a control diet (i.e., offered fresh autumn pasture to maintenance requirements: 0.55 MJ ME/kg of measured metabolic BW [BW0.75] per day) or, in addition to the control diet, 1 of 2 supplement amounts (2.5 and 5.0 kg DM/d) of autumn pasture or 1 of 4 supplementary feeds (i.e., a control and 2 levels of feeding for each of 5 feeds: 11 groups of cows). Along with autumn pasture, evaluated feeds included spring pasture silage, maize silage, maize grain, and palm kernel expeller. Adipose and liver tissues were biopsied in wk 4 of the experiment and transcript abundance of genes involved in metabolic pathways associated with energy metabolism, lipolysis, and lipogenesis was determined. Additional feed, irrespective of type, increased BW gain (P < 0.01) and this effect was reflected in the expression of genes in adipose and liver tissue. However, autumn pasture had lower energy-use efficiency than the other feeds. Genes involved in both lipogenesis (ACACA, THRSP, GPAM, GPD1, and LPL) and lipolysis (PNPLA2) were upregulated (P < 0.05) in adipose tissue in response to increased ME intake/kilogram BW0.75. Hepatic expression of APOA1 decreased and that of APOB increased (P < 0.05) in cows offered maize grain and maize silage (i.e., starch-containing feeds). In comparison, pasture-fed cows demonstrated a degree of uncoupling of the somatotropic axis, with lower hepatic transcript abundance of both GHR1A and IGF-1 compared with cows offered any of the other 4 feeds. Changes to gene transcription indicate a possible molecular mechanism for the poor BW gain evident in ruminants consuming autumn

  8. Protein-enriched meal replacements do not adversely affect liver, kidney or bone density: an outpatient randomized controlled trial.

    PubMed

    Li, Zhaoping; Treyzon, Leo; Chen, Steve; Yan, Eric; Thames, Gail; Carpenter, Catherine L

    2010-12-31

    There is concern that recommending protein-enriched meal replacements as part of a weight management program could lead to changes in biomarkers of liver or renal function and reductions in bone density. This study was designed as a placebo-controlled clinical trial utilizing two isocaloric meal plans utilizing either a high protein-enriched (HP) or a standard protein (SP) meal replacement in an outpatient weight loss program. 100 obese men and women over 30 years of age with a body mass index (BMI) between 27 to 40 kg/m2 were randomized to one of two isocaloric weight loss meal plans 1). HP group: providing 2.2 g protein/kg of lean body mass (LBM)/day or 2). SP group: providing 1.1 g protein/kg LBM/day. Meal replacement (MR) was used twice daily (one meal, one snack) for 3 months and then once a day for 9 months. Body weight, lipid profiles, liver function, renal function and bone density were measured at baseline and 12 months. Seventy subjects completed the study. Both groups lost weight (HP -4.29 ± 5.90 kg vs. SP -4.66 ± 6.91 kg, p < 0.01) and there was no difference in weight loss observed between the groups at one year. There was no significant change noted in liver function [AST (HP -2.07 ± 10.32 U/L, p = 0.28; SP 0.27 ± 6.67 U/L, p = 0.820), ALT (HP -1.03 ± 10.08 U/L, p = 0.34; SP -2.6 ± 12.51 U/L, p = 0.24), bilirubin (HP 0.007 ± 0.33, U/L, p = 0.91; SP 0.07 ± 0.24 U/L, p = 0.120), alkaline phosphatase (HP 2.00 ± 9.07 U/L, p = 0.240; SP -2.12 ± 11.01 U/L, p = 0.280)], renal function [serum creatinine (HP 0.31 ± 1.89 mg/dL, p = 0.380; SP -0.05 ± 0.15 mg/dL, p = 0.060), urea nitrogen (HP 1.33 ± 4.68 mg/dL, p = 0.130; SP -0.24 ± 3.03 mg/dL, p = 0.650), 24 hour urine creatinine clearance (HP -0.02 ± 0.16 mL/min, p = 0.480; SP 1.18 ± 7.53 mL/min, p = 0.400), and calcium excretion (HP -0.41 ± 9.48 mg/24 hours, p = 0.830; SP -0.007 ± 6.76 mg/24 hours, p = 0.990)] or in bone mineral density by DEXA (HP 0.04 ± 0.19 g/cm2, p = 0.210; SP -0.03 ± 0

  9. Protein-enriched meal replacements do not adversely affect liver, kidney or bone density: an outpatient randomized controlled trial

    PubMed Central

    2010-01-01

    Background There is concern that recommending protein-enriched meal replacements as part of a weight management program could lead to changes in biomarkers of liver or renal function and reductions in bone density. This study was designed as a placebo-controlled clinical trial utilizing two isocaloric meal plans utilizing either a high protein-enriched (HP) or a standard protein (SP) meal replacement in an outpatient weight loss program. Subjects/methods 100 obese men and women over 30 years of age with a body mass index (BMI) between 27 to 40 kg/m2 were randomized to one of two isocaloric weight loss meal plans 1). HP group: providing 2.2 g protein/kg of lean body mass (LBM)/day or 2). SP group: providing 1.1 g protein/kg LBM/day. Meal replacement (MR) was used twice daily (one meal, one snack) for 3 months and then once a day for 9 months. Body weight, lipid profiles, liver function, renal function and bone density were measured at baseline and 12 months. Results Seventy subjects completed the study. Both groups lost weight (HP -4.29 ± 5.90 kg vs. SP -4.66 ± 6.91 kg, p < 0.01) and there was no difference in weight loss observed between the groups at one year. There was no significant change noted in liver function [AST (HP -2.07 ± 10.32 U/L, p = 0.28; SP 0.27 ± 6.67 U/L, p = 0.820), ALT (HP -1.03 ± 10.08 U/L, p = 0.34; SP -2.6 ± 12.51 U/L, p = 0.24), bilirubin (HP 0.007 ± 0.33, U/L, p = 0.91; SP 0.07 ± 0.24 U/L, p = 0.120), alkaline phosphatase (HP 2.00 ± 9.07 U/L, p = 0.240; SP -2.12 ± 11.01 U/L, p = 0.280)], renal function [serum creatinine (HP 0.31 ± 1.89 mg/dL, p = 0.380; SP -0.05 ± 0.15 mg/dL, p = 0.060), urea nitrogen (HP 1.33 ± 4.68 mg/dL, p = 0.130; SP -0.24 ± 3.03 mg/dL, p = 0.650), 24 hour urine creatinine clearance (HP -0.02 ± 0.16 mL/min, p = 0.480; SP 1.18 ± 7.53 mL/min, p = 0.400), and calcium excretion (HP -0.41 ± 9.48 mg/24 hours, p = 0.830; SP -0.007 ± 6.76 mg/24 hours, p = 0.990)] or in bone mineral density by DEXA (HP 0.04

  10. Does the standard vs piggyback surgical technique affect the development of early acute renal failure after orthotopic liver transplantation?

    PubMed

    Cabezuelo, J B; Ramirez, P; Acosta, F; Torres, D; Sansano, T; Pons, J A; Bru, M; Montoya, M; Rios, A; Sánchez Bueno, F; Robles, R; Parrilla, P

    2003-08-01

    The objective of this study was to evaluate the effect of the surgical technique on postoperative renal function during the first week after liver transplantation (OLT). We performed a retrospective study of 184 consecutive OLT. Criteria for acute renal failure were: serum creatinine >1.5 mg/dL, an increase by 50% in the baseline serum creatinine, or oliguria requiring renal replacement therapy. The distribution of patients according to the surgical technique was: standard (n=84), venovenous bypass (n=20), and piggyback (n=80). Other variables analyzed were: intraoperative requirement for blood products, treatment with adrenergic agonists, intraoperative complications, and postreperfusion syndrome. Univariate analysis showed the following parameters to be significantly related to postoperative renal failure: intraoperative fresh frozen plasma and cryoprecipitate requirements, intraoperative complications, postreperfusion syndrome, need for noradrenaline or dobutamine, standard surgical technique versus piggyback (39% vs 18%, P<.01) and venovenous vs piggyback (50% vs 18%, P<.01). Logistic regression analysis identified the following variables as having independent prognostic value: (1) Standard surgical technique vs piggyback (OR=3.3, P=.01); (2) venovenous vs piggyback (OR=4.7, P=.02); and (3) >20 U cryoprecipitate requirement (OR=1.04, P=.01). In conclusion, compared with the piggyback technique, the standard surgical technique appears to be an independent risk factor for postoperative acute renal failure. When venovenous bypass is used in patients who do not tolerate trial clamping of inferior vena cava, it does not reduce the incidence of postoperative renal failure. Finally, the piggyback technique significantly reduces the probability of acute renal failure after liver transplantation.

  11. Fetal Hypothalamus-Pituitary-Adrenal Responses to Estradiol Sulfate

    PubMed Central

    2011-01-01

    Estradiol (E2) is an important modifier of the activity of the fetal hypothalamus-pituitary-adrenal axis. We have reported that estradiol-3-sulfate (E2SO4) circulates in fetal blood in far higher concentrations than E2 and that the fetal brain expresses steroid sulfatase, required for local deconjugation of E2SO4. We performed the present study to test the hypothesis that chronic infusion of E2SO4 chronically increases ACTH and cortisol secretion and that it shortens gestation. Chronically catheterized fetal sheep were treated with E2SO4 intracerebroventricular (n = 5), E2SO4 iv (n = 4), or no steroid infusion (control group, n = 5). Fetuses were subjected to arterial blood sampling every other day until spontaneous birth for plasma hormone analysis. Treatment with E2SO4 attenuated preparturient increases in ACTH secretion near term without affecting the ontogenetic rise in plasma cortisol. Infusion of E2SO4 intracerebroventricularly significantly increased plasma E2, plasma E2SO4, and plasma progesterone and shortened gestation compared with all other groups. These results are consistent with the conclusion that E2SO4: 1) interacts with the hypothalamus-pituitary-adrenal axis primarily by stimulating cortisol secretion and inhibiting ACTH and pro-ACTH secretion by negative feedback; and 2) stimulates the secretion of E2 and E2SO4. We conclude that the endocrine response to E2SO4 in the fetus is not identical with the response to E2. PMID:21952234

  12. Yucca schidigera can promote rabbit growth, fecundity, affect the release of hormones in vivo and in vitro, induce pathological changes in liver, and reduce ovarian resistance to benzene.

    PubMed

    Földešiová, Martina; Baláži, Andrej; Chrastinová, Ľubica; Pivko, Juraj; Kotwica, Jan; Harrath, Abdel Halim; Chrenek, Peter; Sirotkin, Alexander V

    2017-08-01

    This study evaluated the effect of Yucca schidigera (YS) extract on the physiological, reproductive, and endocrine indexes of New Zealand White rabbit does. Six-week-old rabbit does were fed a standard diet (control group) or a diet enriched with 5 or 20g of Y powder extract per 100-kg feed mixture for 350days. The does were artificially inseminated after induction of superovulation. Weight gain; conception and kindling rate; viability of pups and mothers; histopathological state of liver and muscle; plasma levels of progesterone (P4), oxytocin (OT), and prostaglandin F (PGF); and the release of P4, insulin-like growth factor I (IGF-I), OT, and PGF by isolated ovarian fragments and their response to the addition of benzene were analyzed. YS extract supplementation promoted weight gain and induced histopathological changes in the liver (creased vacuolization and occurrence of fuchsinophile inclusions in hepatocytes, liver fibrosis, hyperemia, occurrence of Kupffer cells, signs of necrosis and inflammation). YS consumption was not associated with changes in muscle (occurrence of fuchsinophile inclusions and signs of atrophy, interstitial edema, and inflammation), although Y2 increased muscle vascularization. YS supplementation increased conception and kindling rates but did not affect viability of pups or adult animals. Moreover, it enhanced plasma OT and PGF levels; plasma P4 concentration was increased by low-dose YS, but decreased by high-dose YS. Cultured ovarian fragments isolated from YS-fed does released more P4 and PGF and less IGF-I than ovarian fragments of control animals. However, YS supplementation did not affect ovarian OT release. Benzene alone did not influence the release of hormones by ovaries of control does. YS supplementation induced the inhibitory effect of benzene on the release of PGF, but not on other ovarian hormones. Collectively, these results suggest that dietary supplementation of YS extract can stimulate rabbit performance (growth and

  13. Microenvironment of liver regeneration in liver cancer.

    PubMed

    Li, Han-Min; Ye, Zhi-Hua

    2017-07-01

    The occurrence and development of liver cancer are essentially the most serious outcomes of uncontrolled liver regeneration. The progression of liver cancer is inevitably related to the abnormal microenvironment of liver regeneration. The deterioration observed in the microenvironment of liver regeneration is a necessary condition for the occurrence, development and metastasis of cancer. Therefore, the use of a technique to prevent and treat liver cancer via changes in the microenvironment of liver regeneration is a novel strategy. This strategy would be an effective way to delay, prevent or even reverse cancer occurrence, development and metastasis through an improvement in the liver regeneration microenvironment along with the integrated regulation of multiple components, targets, levels, channels and time sequences. In addition, the treatment of "tonifying Shen (Kidney) to regulate liver regeneration and repair by affecting stem cells and their microenvironment" can regulate "the dynamic imbalance between the normal liver regeneration and the abnormal liver regeneration"; this would improve the microenvironment of liver regeneration, which is also a mechanism by which liver cancer may be prevented or treated.

  14. Acute exposure to solar simulated ultraviolet radiation affects oxidative stress-related biomarkers in skin, liver and blood of hairless mice.

    PubMed

    Svobodová, Alena Rajnochová; Galandáková, Adéla; Sianská, Jarmila; Doležal, Dalibor; Ulrichová, Jitka; Vostálová, Jitka

    2011-01-01

    The ultraviolet (UV) region of solar radiation is a critical factor in the initiation and development of a number of skin diseases. However, it is not only skin which is directly exposed to solar light that is affected by UV radiation, through low molecular weight mediators, generated upon irradiation, "non-skin" tissues can also be affected. The aim of this study was to examine in detail, the acute effects of UVA and UVB wavebands on hairless mice. Female SKH-1 hairless mice were exposed to a single dose of UVB (200, 800 mJ/cm(2)) or UVA (10, 20 J/cm(2)) using a solar simulator. The effects on haematological parameters, activity and/or expression of antioxidant enzymes, level of glutathione (GSH), markers of oxidative damage (lipid peroxidation and carbonylated proteins) were analysed in erythrocytes, plasma, liver and whole skin homogenates. No macroscopic changes were observed either 4 or 24 h after UVA/UVB exposure. The blood count showed a significant increase in leukocyte number and reduction of platelets 4 h following UVA and UVB irradiation, which disappeared 24 h after irradiation except for the higher UVA dose. Changes in oxidative stress-related parameters, particularly activity of catalase (CAT) and superoxide dismutase (SOD) and level of GSH and lipid peroxidation products, were found in skin, erythrocytes and liver. The expression of several enzymes (CAT, SOD, glutathione transferase (GST), nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (NQO1) and hem oxygenase-1 (HO-1)) in skin was affected following UVA and UVB radiation. Increase in carbonylated proteins was found in plasma and skin samples.

  15. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Comparison of three extraction methods for 17beta-estradiol in sand, bentonite, and organic-rich silt loam.

    PubMed

    Chun, Soul; Lee, Jaehoon; Geyer, Roland; White, David C

    2005-01-01

    Extraction is an important procedure for samples that contain soil because other compounds in soil may affect analysis of estrogens. This study was conducted to evaluate three different extraction methods for 17beta-estradiol in soil. Sand, bentonite, and organic-rich silt loam were spiked with 1 mg kg(-1) of 17beta-estradiol as a model compound of estrogens. 17beta-estradiol and its metabolites, estrone and estriol, were extracted using (i) a modified Bligh and Dyer extraction, (ii) a pressurized fluid extraction, and (iii) a diethyl ether extraction, and measured by liquid chromatography tandem mass spectrometry. There were significant differences in the extraction efficiency for 17beta-estradiol among the extraction methods and the soils: the efficiencies ranged from 10% to 97%. Overall, the diethyl ether extraction method had the largest efficiency of 17beta-estradiol with 45% and 57% for bentonite and silt loam, respectively. Transformation of 17beta-estradiol to estrone and estriol in the different extraction methods was less than 3.6% during the extraction procedures. This study underlined the importance of sample preparation for estrogen analysis in soil samples.

  17. Suppressive effects of estradiol on 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated transcriptional activation of murine Cyp1a-1 in mouse hepatoma Hepa 1c1c7 cells.

    PubMed

    Jeong, H G; Lee, S S

    1998-11-27

    Cultured mouse hepatoma Hepa lclc7 cells were treated with either estradiol or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or in combination to assess the role of estradiol in the process of Cypla-1 induction. Estradiol at a concentration as high as 1 microM slightly increased the activity of Cypla-1-specific 7-ethoxyresorufin O-deethylase (EROD); in contrast, TCDD-induced EROD activity and Cypla-1 mRNA levels were markedly reduced in the concomitant treatment of TCDD and estradiol in a dose-dependent manner. Treatment with tamoxifen, an anti-estrogen which acts through the estrogen receptor, did not affect the suppressive effects of estradiol on TCDD-induced EROD activity. Electrophoretic mobility shift assay using nuclear extract of cells revealed that estradiol reduced transformation of the Ah receptor to the form capable of specifically binding to an oligonucleotide containing dioxin-response element (DRE) sequence. Consistent with this, estradiol decreased TCDD-induced increased chloramphenicol acetyltransferase (CAT) activity from a DRE-containing CAT reporter plasmid after transient transfection into the cells. The levels of the cytosolic [3H]TCDD-Ah receptor complex were reduced by estradiol in competitive Ah receptor binding assay using [3H]TCDD. This study demonstrated that estradiol acts as an antagonist to TCDD and can regulate Cyp1a-1 expression in an Ah receptor-dependent manner but not through estradiol receptor in Hepa 1c1c7 cells.

  18. Specific estrogen-binding protein of rat liver and sex steroid metabolism

    SciTech Connect

    Shchelkunova, T.A.; Rozen, V.B.; Smirnov, A.N.

    1986-01-01

    Model experiments were conducted to study the effect of a highly purified preparation of specific estrogen-binding protein (SEBP) on the intensity of estradiol and testosterone metabolism under the influence of enzymes in liver homogenate from female rats, not containing SEBP. The liver of mature female rats was homogenized in two volumes of 50 mM Tris-HCl buffer, pH 7.5, containing 600 mg% of glucose. The tritium-steroid was preincubated for 15 min at 0-4 C with 0-4 microg of the preparation of SEBP (200 microl). A standard preparation of partially purified SEBP was obtained from liver cystosol of mature male rats; affinity chromatography on estradiolagarose was used. It is shown that SEBP can really take part in regulation of the dynamics of sex steroids in the liver. E/sub 1/ did not affect the metabolic rate of H 3-E/sub 2/ by liver homogenate from females, but caused marked acceleration of H 3-E/sub 2/ metabolism by male liver homogenate.

  19. Progesterone and estradiol synergistically promote the lung metastasis of tuberin-deficient cells in a preclinical model of lymphangioleiomyomatosis

    PubMed Central

    Sun, Yang; Zhang, Erik; Lao, Taotao; Pereira, Ana M.; Li, Chenggang; Xiong, Li; Morrison, Tasha; Haley, Kathleen J.; Zhou, Xiaobo; Yu, Jane J.

    2014-01-01

    Lymphangioleiomyomatosis (LAM) is a female-predominant lung disease that can lead to respiratory failure. LAM cells typically have inactivating TSC2 mutations, leading to mTORC1 hyperactivation. The gender specificity of LAM suggests that female hormones contribute to disease progression. Clinical findings indicate that estradiol exacerbates LAM behaviors and symptoms. Although hormonal therapy with progesterone has been employed, the benefit in LAM improvement has not been achieved. We have previously found that estradiol promotes the survival and lung metastasis of cells lacking tuberin in a preclinical model of LAM. In this study, we hypothesize that progesterone alone or in combination with estradiol promote metastatic behaviors of TSC2-deficient cells. In cell culture models of TSC2-deficient LAM patient-derived and rat uterine leiomyoma-derived cells, we found that progesterone treatment or progesterone plus estradiol resulted in increased phosphorylation of Akt and ERK1/2, induced the proliferation, and enhanced the migration and invasiveness. In addition, treatment of progesterone plus estradiol synergistically decreased the levels of reactive oxygen species, and enhanced cell survival under oxidative stress. In a murine model of LAM, treatment of progesterone plus estradiol promoted the growth of xenograft tumors; however, progesterone treatment did not affect the development of xenograft tumors of Tsc2-deficient cells. Importantly, treatment of progesterone plus estradiol resulted in alteration of lung morphology, and significantly increased the number of lung micrometastases of Tsc2-deficient cells compared with estradiol treatment alone. Collectively, these data indicate that progesterone increases the metastatic potential of TSC2-deficient LAM patient-derived cells in vitro and lung metastasis in vivo. Thus, targeting progesterone-mediated signaling events may have therapeutic benefit for LAM and possibly other hormonally dependent cancers. PMID

  20. Neuroprotection by estradiol: a role of aromatase against spine synapse loss after blockade of GABA(A) receptors.

    PubMed

    Zhou, Lepu; Lehan, Nadine; Wehrenberg, Uwe; Disteldorf, Erik; von Lossow, Richard; Mares, Ute; Jarry, Hubertus; Rune, Gabriele M

    2007-01-01

    Estrogen has been suggested to be pro-epileptic by reducing GABA synthesis, resulting in increased spine density and a decreased threshold for seizures in the hippocampus, which, once they occur, are characterized by a dramatic spine loss in the affected brain areas. As considerable amounts of estradiol are synthesized in the hippocampus, in this study we focused on aromatase, the rate-limiting enzyme in estrogen synthesis in order to examine the role of locally synthesized estrogens in epilepsy. To this end, we first examined the effects of letrozole, a potent aromatase inhibitor, on GABA metabolism in single interneurons of hippocampal dispersion cultures. Letrozole downregulated estradiol release into the medium, as well as glutamate decarboxylase (GAD) expression and GABA synthesis, and decreased the number of GAD positive cells in the cultures. Next, we counted spine synapses and measured estradiol release of hippocampal slice cultures, in which GABA(A) receptors had been blocked by bicuculline, in order to mimic epileptic activity. Treatment of slice cultures with bicuculline resulted in a dramatic decrease in the number of spine synapses and in a significant suppression of estrogen synthesis. The decrease in synapse number in response to bicuculline was restored by combined application of estradiol and bicuculline. Surprisingly, estradiol alone had no effect on either spine synapse number or on GAD expression and GABA synthesis. "Rescue" of synapse number in "epileptic slices" by estradiol and maintenance of GABA metabolism by hippocampus-derived estradiol points to a neuroprotective role of aromatase in epilepsy. Re-filling of estradiol stores after their depletion due to overexcitation may therefore add to therapeutical strategies in epilepsy.

  1. Skeletal muscle mass to visceral fat area ratio is an important determinant affecting hepatic conditions of non-alcoholic fatty liver disease.

    PubMed

    Shida, Takashi; Akiyama, Kentaro; Oh, Sechang; Sawai, Akemi; Isobe, Tomonori; Okamoto, Yoshikazu; Ishige, Kazunori; Mizokami, Yuji; Yamagata, Kenji; Onizawa, Kojiro; Tanaka, Hironori; Iijima, Hiroko; Shoda, Junichi

    2017-08-08

    Not only obesity but also sarcopenia is associated with NAFLD. The influence of altered body composition on the pathophysiology of NAFLD has not been fully elucidated. The aim of this study is to determine whether skeletal muscle mass to visceral fat area ratio (SV ratio) affects NAFLD pathophysiology. A total of 472 subjects were enrolled. The association between SV ratio and NAFLD pathophysiological factors was assessed in a cross-sectional nature by stratification analysis. When the SV ratio was stratified by quartiles (Q 1-Q 4), the SV ratio showed a negative relationship with the degree of body mass index, HOMA-IR, and liver stiffness (Q 1, 8.9 ± 7.5 kPa, mean ± standard deviation; Q 2, 7.5 ± 6.2; Q 3, 5.8 ± 3.7; Q 4, 5.0 ± 1.9) and steatosis (Q 1, 282 ± 57 dB/m; Q 2, 278 ± 58; Q 3, 253 ± 57; Q 4, 200 ± 42) measured by transient elastography. Levels of leptin and biochemical markers of liver cell damage, liver fibrosis, inflammation and oxidative stress, and hepatocyte apoptosis were significantly higher in subjects in Q 1 than in those in Q 2, Q 3, or Q 4. Moreover, fat contents in femoral muscles were significantly higher in subjects in Q 1 and the change was associated with weakened muscle strength. In logistic regression analysis, NAFLD subjects with the decreased SV ratio were likely to have an increased risk of moderate-to-severe steatosis and that of advanced fibrosis. Decreased muscle mass coupled with increased visceral fat mass is closely associated with an increased risk for exacerbating NAFLD pathophysiology.

  2. Substantial replacement of lactose with fat in a high-lactose milk replacer diet increases liver fat accumulation but does not affect insulin sensitivity in veal calves.

    PubMed

    Pantophlet, A J; Gerrits, W J J; Vonk, R J; van den Borne, J J G C

    2016-12-01

    In veal calves, the major portion of digestible energy intake originates from milk replacer (MR), with lactose and fat contributing approximately 45 and 35%, respectively. In veal calves older than 4 mo, prolonged high intakes of MR may lead to problems with glucose homeostasis and insulin sensitivity, ultimately resulting in sustained insulin resistance, hepatic steatosis, and impaired animal performance. The contribution of each of the dietary energy sources (lactose and fat) to deteriorated glucose homeostasis and insulin resistance is currently unknown. Therefore, an experiment was designed to compare the effects of a high-lactose and a high-fat MR on glucose homeostasis and insulin sensitivity in veal calves. Sixteen male Holstein-Friesian calves (120±2.8kg of BW) were assigned to either a high-lactose (HL) or a high-fat (HF) MR for 13 consecutive weeks. After at least 7 wk of adaptation, whole-body insulin sensitivity and insulin secretion were assessed by euglycemic-hyperinsulinemic and hyperglycemic clamps, respectively. Postprandial blood samples were collected to assess glucose, insulin, and triglyceride responses to feeding, and 24-h urine was collected to quantify urinary glucose excretion. At the end of the trial, liver and muscle biopsies were taken to assess triglyceride contents in these tissues. Long-term exposure of calves to HF or HL MR did not affect whole-body insulin sensitivity (averaging 4.2±0.5×10(-2) [(mg/kg∙min)/(μU/mL)]) and insulin secretion. Responses to feeding were greater for plasma glucose and tended to be greater for plasma insulin in HL calves than in HF calves. Urinary glucose excretion was substantially higher in HL calves (75±13g/d) than in HF calves (21±6g/d). Muscle triglyceride content was not affected by treatment and averaged 4.5±0.6g/kg, but liver triglyceride content was higher in HF calves (16.4±0.9g/kg) than in HL calves (11.2±0.7g/kg), indicating increased hepatic fat accumulation. We conclude that

  3. High levels of dietary phytosterols affect lipid metabolism and increase liver and plasma TAG in Atlantic salmon (Salmo salar L.).

    PubMed

    Liland, Nina S; Espe, Marit; Rosenlund, Grethe; Waagbø, Rune; Hjelle, Jan I; Lie, Øyvind; Fontanillas, Ramon; Torstensen, Bente E

    2013-12-14

    Replacing dietary fishmeal (FM) and fish oil (FO) with plant ingredients in Atlantic salmon (Salmo salar L.) diets decreases dietary cholesterol and introduces phytosterols. The aim of the present study was to assess the effect of dietary sterol composition on cholesterol metabolism in Atlantic salmon. For this purpose, two dietary trials were performed, in which Atlantic salmon were fed either 100 % FM and FO (FM-FO) diet or one of the three diets with either high (80 %) or medium (40 %) plant protein (PP) and a high (70 %) or medium (35 %) vegetable oil (VO) blend (trial 1); or 70 % PP with either 100 % FO or 80 % of the FO replaced with olive, rapeseed or soyabean oil (trial 2). Replacing ≥ 70 % of FM with PP and ≥ 70 % of FO with either a VO blend or rapeseed oil increased plasma and liver TAG concentrations. These diets contained high levels of phytosterols and low levels of cholesterol. Fish fed low-cholesterol diets, but with less phytosterols, exhibited an increased expression of genes encoding proteins involved in cholesterol uptake and synthesis. The expression of these genes was, however, partially inhibited in rapeseed oil-fed fish possibly due to the high dietary and tissue phytosterol:cholesterol ratio. Atlantic salmon tissue and plasma cholesterol concentrations were maintained stable independent of the dietary sterol content.

  4. Sexual dimorphism of liver metastasis by murine pancreatic neuroendocrine tumors is affected by expression of complement C5.

    PubMed

    Contractor, Tanupriya; Kobayashi, Shinta; da Silva, Edaise; Clausen, Richard; Chan, Chang; Vosburgh, Evan; Tang, Laura H; Levine, Arnold J; Harris, Chris R

    2016-05-24

    In a mouse model for neuroendocrine tumors of the pancreas (PanNETs), liver metastasis occurred at a higher frequency in males. Male mice also had higher serum and intratumoral levels of the innate immunity protein complement C5. In mice that lost the ability to express complement C5, there was a lower frequency of metastasis, and males no longer had a higher frequency of metastasis than females. Treatment with PMX53, a small molecule antagonist of C5aR1/CD88, the receptor for complement C5a, also reduced metastasis. Mice lacking a functional gene for complement C5 had smaller primary tumors, which were less invasive and lacked the CD68+ macrophages that have previously been associated with metastasis in this type of tumor. This is the first report of a gene that causes sexual dimorphism of metastasis in a mouse model. In the human disease, which also shows sexual dimorphism for metastasis, clinically advanced tumors expressed more complement C5 than less advanced tumors.

  5. Gestational and postnatal protein deficiency affects postnatal development and histomorphometry of liver, kidneys, and ovaries of female rats' offspring.

    PubMed

    Almeida, Fernanda R C L; Silva, Gerluza A B; Fiúza, Aparecida T L; Chianca, Deoclécio A; Ferreira, Anderson J; Chiarini-Garcia, Hélio

    2012-04-01

    Pre- and postnatal protein deficiency may lead to decreased foetal intra-uterine development and postnatal growth, which is common in developing countries. The present study aimed to investigate the consequences of a low-protein intake during gestation and postnatally on adult female rats' offspring. Female rats were given either a control or a protein-deficient diet throughout the gestation and lactation periods. A subset of females was killed at day 20 of pregnancy for foetal and placental measurements. Another subset of females farrowed and the number, length, and weight of the offspring were measured. After weaning, the offspring received the same diet as their dams until 70 days of age. They were sacrificed, and some organs were weighed and collected for histomorphometrical analyses. Placental weight and size and foetal weight were lower in protein-deficient dams. The weight and length of pups at birth were also lower in the deficient group. The organs to body weight ratio were higher in the deficient animals at 70 days of age. The protein-deficient female offspring had a smaller ovarian area, greater numbers of primordial follicles and developing follicles per square millimetres of ovarian cortex, and no corpora lutea. The liver showed smaller nuclear diameter of the hepatocytes and height of the hepatocytes cords. The kidneys showed smaller cortical area with reduced glomerular number and diameter. These results provide the first evidence of the histomorphological changes of the association between gestational and postnatal protein deficiency in female rats' offspring.

  6. Pyruvate kinase M2 affects liver cancer cell behavior through up-regulation of HIF-1α and Bcl-xL in culture.

    PubMed

    Dong, Tianfu; Yan, Youde; Chai, Hao; Chen, Shenglin; Xiong, Xinkui; Sun, Daoyi; Yu, Yue; Deng, Lei; Cheng, Feng

    2015-02-01

    Cancer cells consume large amounts of glucose to produce lactate, even in the presence of ample oxygen. This phenomenon is known as the Warburg effect. The pyruvate kinase promotes aerobic glycolysis, and the pyruvate kinase M2 isoform (PKM2) is highly expressed in many cancer cells. Although the Warburg effect is a hallmark of cancer, the mechanism by which PKM2 contributes to the Warburg effect, and its role in tumor growth remain to be defined. We proposed that PKM2 activates transcription of hypoxia inducible factor-1α (HIF-1α) by phosphorylating STAT3 (signal transducer and activator of transcription 3) at Y705 (tyrosine 705) as a plausible mechanism for liver cancer cell proliferation. In the current study, we observed that PKM2 was over-expressed in hepatocellular carcinoma (HCC) tissues compared to adjacent normal tissues. The experiments further indicate that nuclear PKM2 is an active protein kinase in cultured cells. Knockdown of PKM2 affected the levels of HIF-1α and Bcl-xL (B-cell lymphoma-extra large), suggesting that PKM2 plays an important role in promoting cell proliferation. In conclusion, the current findings demonstrate that PKM2 is an active protein kinase, and promotes liver cancer cell proliferation by up-regulating HIF-1α and Bcl-xL expression. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  7. Ubiquinol affects the expression of genes involved in PPARα signalling and lipid metabolism without changes in methylation of CpG promoter islands in the liver of mice.

    PubMed

    Schmelzer, Constance; Kitano, Mitsuaki; Hosoe, Kazunori; Döring, Frank

    2012-03-01

    Coenzyme Q(10) is an essential cofactor in the respiratory chain and serves as a potent antioxidant in biological membranes. Recent studies in vitro and in vivo provide evidence that Coenzyme Q(10) is involved in inflammatory processes and lipid metabolism via gene expression. To study these effects at the epigenomic level, C57BL6J mice were supplemented for one week with reduced Coenzyme Q(10) (ubiquinol). Afterwards, gene expression signatures and DNA promoter methylation patterns of selected genes were analysed. Genome-wide transcript profiling in the liver identified 1112 up-regulated and 571 down-regulated transcripts as differentially regulated between ubiquinol-treated and control animals. Text mining and GeneOntology analysis revealed that the "top 20" ubiquinol-regulated genes play a role in lipid metabolism and are functionally connected by the PPARα signalling pathway. With regard to the ubiquinol-induced changes in gene expression of about +3.14-fold (p≤0.05), +2.18-fold (p≤0.01), and -2.13-fold (p≤0.05) for ABCA1, ACYP1, and ACSL1 genes, respectively, hepatic DNA methylation analysis of 282 (sense orientation) and 271 (antisense) CpG units in the respective promoter islands revealed no significant effect of ubiquinol. In conclusion, ubiquinol affects the expression of genes involved in PPARα signalling and lipid metabolism without changing the promoter DNA methylation status in the liver of mice.

  8. Compared with Powdered Lutein, a Lutein Nanoemulsion Increases Plasma and Liver Lutein, Protects against Hepatic Steatosis, and Affects Lipoprotein Metabolism in Guinea Pigs.

    PubMed

    Murillo, Ana Gabriela; Aguilar, David; Norris, Gregory H; DiMarco, Diana M; Missimer, Amanda; Hu, Siqi; Smyth, Joan A; Gannon, Sarah; Blesso, Christopher N; Luo, Yangchao; Fernandez, Maria Luz

    2016-10-01

    It is not clear how oil-in-water nanoemulsions of lutein may affect bioavailability and consequently alter lipoprotein metabolism, oxidative stress, and inflammation. The bioavailability as well as effects of a powdered lutein (PL) and an oil-in-water lutein nanoemulsion (NANO; particle size: 254.2 nm; polydispersity index: 0.29; and ζ-potential: -65 mV) on metabolic variables in liver, plasma, and adipose tissue in a guinea pig model of hepatic steatosis were evaluated. Twenty-four 2-mo-old male Hartley guinea pigs, weighing 200-300 g (n = 8/group), were fed diets containing 0.25 g cholesterol/100 g to induce liver injury for the duration of the study. They were allocated to control (0 mg lutein), PL (3.5 mg/d), or NANO (3.5 mg/d) groups. After 6 wk, plasma, liver, and adipose tissue were collected for determination of lutein, plasma lipids, tissue cholesterol, and inflammatory cytokines. The NANO group had 2-fold higher concentrations of lutein in plasma (P < 0.001) and 1.6-fold higher concentrations in liver (P < 0.001) than did the PL group, indicating greater bioavailability of this carotenoid. The NANO group also had 24% lower hepatic steatosis scores (P < 0.05), 31% lower hepatic cholesterol accumulation (P < 0.05), and 64% lower plasma alanine aminotransferase (P < 0.05) than did the control group. Hepatic oxidized LDL was 55% lower in both the PL and NANO groups than in the control group (P < 0.05). In plasma, the NANO group had 2-fold higher concentrations of LDL and HDL cholesterol as well as a 2-fold higher number of VLDL, LDL, and HDL particles than did the other 2 groups as evaluated by nuclear magnetic resonance. Furthermore, the NANO group had 15% higher concentrations of free cholesterol in adipose tissue, resulting in higher concentrations of inflammatory markers, than did the other 2 groups. These results indicate that, although this lutein nanoemulsion exerted protective effects against hepatic steatosis, plasma lipoproteins and adipose tissue

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

    PubMed

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

    2015-08-05

    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. 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. 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 = 0.0009), and E2 persisted whereas the

  10. 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

  11. Vitamin B1 Deficiency Does not Affect the Liver Concentrations of the Other Seven Kinds of B-Group Vitamins in Rats

    PubMed Central

    Shibata, Katsumi; Shimizu, Atsushi; Fukuwatari, Tsutomu

    2013-01-01

    We aimed to determine the effects of vitamin B1 deficiency on vitamin contents of urine, liver, and blood. In the current study, rats were divided into 3 groups (n = 5, each group): the first was freely fed a complete diet (ad lib-fed control group); the second freely fed a vitamin B1-free diet (vitamin B1 deficient group); and the third pair-fed a complete diet with the same amounts of the vitamin B1 deficient group (pair-fed control group). The experimental period was for 15 days. The blood concentrations of vitamin B2, PLP, vitamin B12, folic acid, and biotin were lower in the pair-fed control than in the ad lib-fed control and those of nicotinamide and pantothenic acid were the same. We conclude that Vitamin B1 deficiency did not affect concentrations of the other B-group vitamins. PMID:23935367

  12. Vitamin B1 Deficiency Does not Affect the Liver Concentrations of the Other Seven Kinds of B-Group Vitamins in Rats.

    PubMed

    Shibata, Katsumi; Shimizu, Atsushi; Fukuwatari, Tsutomu

    2013-01-01

    We aimed to determine the effects of vitamin B1 deficiency on vitamin contents of urine, liver, and blood. In the current study, rats were divided into 3 groups (n = 5, each group): the first was freely fed a complete diet (ad lib-fed control group); the second freely fed a vitamin B1-free diet (vitamin B1 deficient group); and the third pair-fed a complete diet with the same amounts of the vitamin B1 deficient group (pair-fed control group). The experimental period was for 15 days. The blood concentrations of vitamin B2, PLP, vitamin B12, folic acid, and biotin were lower in the pair-fed control than in the ad lib-fed control and those of nicotinamide and pantothenic acid were the same. We conclude that Vitamin B1 deficiency did not affect concentrations of the other B-group vitamins.

  13. Maternal weight gain induced by an obesogenic diet affects adipose accumulation, liver weight, and insulin homeostasis in the rat offspring depending on the sex.

    PubMed

    Cordero, P; Gomez-Uriz, A M; Milagro, F I; Campion, J; Martinez, J A

    2012-12-01

    The aim of this research was to analyze the influence of the maternal dietary intake before pregnancy, as well as the parental impact on the response to a transgenerational high-fat-diet in rats. Ten female Wistar rats were fed a standard or a high-fat-sucrose (HFS) diet in the 8 weeks prior to pregnancy. Adult offsprings were assigned to a control or obesogenic diet for 8 weeks. Then, rat tissues and plasma samples were collected for analyzing tissue weight, liver triglycerides, and biochemical parameters such as triglycerides, HDL cholesterol, glucose, and insulin levels. The offspring of rats fed a HFS diet gained less weight when they were fed the same diet than those fed a HFS diet combined with maternal control diet. Insulin levels were higher in rats fed a HFS diet (p<0.05) in both sexes; however, maternal HFS diet reversed, partially in males and total- ly in females, this hormonal imbalance. In male newborns, diet-induced maternal weight gain before pregnancy significantly influenced visceral (R 2 =0.373) and subcutaneous (R 2 =0.239) adipose deposition as well as liver weight (R 2 =0.130). Paternal genetic make-up was also a relevant factor affecting adiposity in both sexes (R 2 =0.333 in visceral fat; R 2 =0.183 in subcutaneous fat in males, and 0.292 and 0.282, respectively in females) as well as plasma triglycerides (R 2 =0.193 in males and R 2 =0.251 in females). The genetic parental background and pre-natal maternal diet are important factors in the response to a hypercaloric diet and affect body composition and glucose homeostasis traits, including insulin secretion and homeostatic model assessment index.

  14. Seizure facilitating activity of the oral contraceptive ethinyl estradiol.

    PubMed

    Younus, Iyan; Reddy, Doodipala Samba

    2016-03-01

    Contraceptive management is critical in women with epilepsy. Although oral contraceptives (OCs) are widely used by many women with epilepsy, little is known about their impact on epileptic seizures and epileptogenesis. Ethinyl estradiol (EE) is the primary component of OC pills. In this study, we investigated the pharmacological effect of EE on epileptogenesis and kindled seizures in female mice using the hippocampus kindling model. Animals were stimulated daily with or without EE until generalized stage 5 seizures were elicited. EE treatment significantly accelerated the rate of epileptogenesis. In acute studies, EE caused a significant decrease in the afterdischarge threshold and increased the incidence and severity of seizures in fully-kindled mice. In chronic studies, EE treatment caused a greater susceptibility to kindled seizures. Collectively, these results are consistent with moderate proconvulsant-like activity of EE. Such excitatory effects may affect seizure risk in women with epilepsy taking OC pills.

  15. Changes in brain volume in response to estradiol levels, amphetamine sensitization and haloperidol treatment in awake female rats.

    PubMed

    Madularu, Dan; Kulkarni, Praveen; Ferris, Craig F; Brake, Wayne G

    2015-08-27

    Estrogen has been shown to further ameliorate symptoms when administered in conjunction with antipsychotics in patients with schizophrenia. We have previously shown that chronic haloperidol (HAL) treatment reduces amphetamine (AMPH)-induced locomotor activity in AMPH-sensitized rats, but only when paired with high levels of the estrogen, 17-β estradiol. In addition, we reported estradiol-dependent responses to AMPH in AMPH-sensitized rats as measured by functional magnetic resonance imaging. It is thus clear that estradiol and antipsychotics both affect the rat brain, however the mechanism by which this occurs is unknown. The aim of the current study was to assess this interaction by investigating the effects of estradiol, AMPH and HAL on brain volume changes in awake female rats. Repeated exposure to AMPH resulted in an overall reduction in brain volume, regardless of hormonal status (i.e. no, low or high estradiol). Similarly, chronic HAL treatment further reduced brain volume compared to acute treatment. Hormonal status affected hippocampal volume with rats receiving low estradiol replacement showing larger volume; this difference was no longer significant after repeated exposure to AMPH. Finally, we found changes in volume in response to AMPH throughout hippocampal components (i.e. CA1-CA3 and dentate) as well as components of the mesocortical system. In conclusion, brain volume seems to be influenced by hormonal status, as well as exposure to AMPH and haloperidol treatment. These findings implicate areas where estradiol, amphetamine and antipsychotics may be producing volumetric changes in the brain, pointing the way to where future studies should focus. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. DREAM/calsenilin/KChIP3 modulates strategy selection and estradiol-dependent learning and memory.

    PubMed

    Tunur, Tumay; Stelly, Claire E; Schrader, Laura Ann

    2013-11-18

    Downstream regulatory element antagonist modulator (DREAM)/calsenilin(C)/K⁺ channel interacting protein 3 (KChIP3) is a multifunctional Ca²⁺-binding protein highly expressed in the hippocampus that inhibits hippocampus-sensitive memory and synaptic plasticity in male mice. Initial studies in our lab suggested opposing effects of DR/C/K3 expression in female mice. Fluctuating hormones that occur during the estrous cycle may affect these results. In this study, we hypothesized that DR/C/K3 interacts with 17β-estradiol, the primary estrogen produced by the ovaries, to play a role in hippocampus function. We investigated the role of estradiol and DR/C/K3 in learning strategy in ovariectomized (OVX) female mice. OVX WT and DR/C/K3 knockout (KO) mice were given three injections of vehicle (sesame oil) or 17β-estradiol benzoate (0.25 mg in 100 mL sesame oil) 48, 24, and 2 h before training and testing. DR/C/K3 and estradiol had a time-dependent effect on strategy use in the female mice. Male KO mice exhibited enhanced place strategy relative to WT 24 h after pre-exposure. Fear memory formation was significantly reduced in intact female KO mice relative to intact WT mice, and OVX reduced fear memory formation in the WT, but had no effect in the KO mice. Long-term potentiation in hippocampus slices from female mice was enhanced by circulating ovarian hormones in both WT and DR/C/K3 KO mice. Paired-pulse depression was not affected by ovarian hormones but was reduced in DR/C/K3 KO mice. These results provide the first evidence that DR/C/K3 plays a timing-dependent role in estradiol regulation of learning, memory, and plasticity.

  17. The combination of blueberry juice and probiotics reduces apoptosis of alcoholic fatty liver of mice by affecting SIRT1 pathway.

    PubMed

    Zhu, Juanjuan; Ren, Tingting; Zhou, Mingyu; Cheng, Mingliang

    2016-01-01

    To explore the effects of the combination of blueberry juice and probiotics on the apoptosis of alcoholic fatty liver disease (AFLD). Healthy C57BL/6J mice were used in the control group (CG). AFLD mice models were established with Lieber-DeCarli ethanol diet and evenly assigned to six groups with different treatments: MG (model), SI (SIRT1 [sirtuin type 1] small interfering RNA [siRNA]), BJ (blueberry juice), BJSI (blueberry juice and SIRT1 siRNA), BJP (blueberry juice and probiotics), and BJPSI (blueberry juice, probiotics, and SIRT1 siRNA). Hepatic tissue was observed using hematoxylin and eosin (HE) and Oil Red O (ORO) staining. Biochemical indexes of the blood serum were analyzed. The levels of SIRT1, caspase-3, forkhead box protein O1 (FOXO1), FasL (tumor necrosis factor ligand superfamily member 6), BAX, and Bcl-2 were measured by reverse transcription-polymerase chain reaction and Western blotting. HE and ORO staining showed that the hepatocytes were heavily destroyed with large lipid droplets in MG and SI groups, while the severity was reduced in the CG, BJ, and BJP groups (P<0.05). The levels of superoxide dismutase (SOD), reduced glutathione (GSH), and high-density lipoprotein-cholesterol (HDL-C) were increased in BJ and BJP groups when compared with the model group (P<0.05). In contrast, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total triglycerides (TGs), total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and malondialdehyde (MDA) were lower in BJ and BJP groups than in the model group (P<0.05). The level of SIRT1 was increased, while the levels of FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase-3, BAX, and Bcl-2 were decreased in CG, BJ, and BJP groups (P<0.05). Meanwhile, SIRT1 silence resulted in increase of the levels of FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase-3, BAX, and Bcl-2. The combination of blueberry juice and probiotics reduces apoptosis in AFLD by

  18. The combination of blueberry juice and probiotics reduces apoptosis of alcoholic fatty liver of mice by affecting SIRT1 pathway

    PubMed Central

    Zhu, Juanjuan; Ren, Tingting; Zhou, Mingyu; Cheng, Mingliang

    2016-01-01

    Purpose To explore the effects of the combination of blueberry juice and probiotics on the apoptosis of alcoholic fatty liver disease (AFLD). Methods Healthy C57BL/6J mice were used in the control group (CG). AFLD mice models were established with Lieber–DeCarli ethanol diet and evenly assigned to six groups with different treatments: MG (model), SI (SIRT1 [sirtuin type 1] small interfering RNA [siRNA]), BJ (blueberry juice), BJSI (blueberry juice and SIRT1 siRNA), BJP (blueberry juice and probiotics), and BJPSI (blueberry juice, probiotics, and SIRT1 siRNA). Hepatic tissue was observed using hematoxylin and eosin (HE) and Oil Red O (ORO) staining. Biochemical indexes of the blood serum were analyzed. The levels of SIRT1, caspase-3, forkhead box protein O1 (FOXO1), FasL (tumor necrosis factor ligand superfamily member 6), BAX, and Bcl-2 were measured by reverse transcription-polymerase chain reaction and Western blotting. Results HE and ORO staining showed that the hepatocytes were heavily destroyed with large lipid droplets in MG and SI groups, while the severity was reduced in the CG, BJ, and BJP groups (P<0.05). The levels of superoxide dismutase (SOD), reduced glutathione (GSH), and high-density lipoprotein-cholesterol (HDL-C) were increased in BJ and BJP groups when compared with the model group (P<0.05). In contrast, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total triglycerides (TGs), total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and malondialdehyde (MDA) were lower in BJ and BJP groups than in the model group (P<0.05). The level of SIRT1 was increased, while the levels of FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase-3, BAX, and Bcl-2 were decreased in CG, BJ, and BJP groups (P<0.05). Meanwhile, SIRT1 silence resulted in increase of the levels of FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase-3, BAX, and Bcl-2. Conclusion The combination of blueberry juice and

  19. Percutaneous Radiofrequency Ablation of Colorectal Cancer Liver Metastases: Factors Affecting Outcomes—A 10-year Experience at a Single Center

    PubMed Central

    Shady, Waleed; Petre, Elena N.; Gonen, Mithat; Erinjeri, Joseph P.; Brown, Karen T.; Covey, Anne M.; Alago, William; Durack, Jeremy C.; Maybody, Majid; Brody, Lynn A.; Siegelbaum, Robert H.; D’Angelica, Michael I.; Jarnagin, William R.; Solomon, Stephen B.; Kemeny, Nancy E.

    2016-01-01

    Purpose To identify predictors of oncologic outcomes after percutaneous radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLMs) and to describe and evaluate a modified clinical risk score (CRS) adapted for ablation as a patient stratification and prognostic tool. Materials and Methods This study consisted of a HIPAA-compliant institutional review board–approved retrospective review of data in 162 patients with 233 CLMs treated with percutaneous RFA between December 2002 and December 2012. Contrast material–enhanced CT was used to assess technique effectiveness 4–8 weeks after RFA. Patients were followed up with contrast-enhanced CT every 2–4 months. Overall survival (OS) and local tumor progression–free survival (LTPFS) were calculated from the time of RFA by using the Kaplan-Meier method. Log-rank tests and Cox regression models were used for univariate and multivariate analysis to identify predictors of outcomes. Results Technique effectiveness was 94% (218 of 233). Median LTPFS was 26 months. At univariate analysis, predictors of shorter LTPFS were tumor size greater than 3 cm (P < .001), ablation margin size of 5 mm or less (P < .001), high modified CRS (P = .009), male sex (P = .03), and no history of prior hepatectomy (P = .04) or hepatic arterial infusion chemotherapy (P = .01). At multivariate analysis, only tumor size greater than 3 cm (P = .01) and margin size of 5 mm or less (P < .001) were independent predictors of shorter LTPFS. Median and 5-year OS were 36 months and 31%. At univariate analysis, predictors of shorter OS were tumor size larger than 3 cm (P = .005), carcinoembryonic antigen level greater than 30 ng/mL (P = .003), high modified CRS (P = .02), and extrahepatic disease (EHD) (P < .001). At multivariate analysis, tumor size greater than 3 cm (P = .006) and more than one site of EHD (P < .001) were independent predictors of shorter OS. Conclusion Tumor size of less than 3 cm and ablation margins greater than 5 mm

  20. Investigation of testosterone, androstenone, and estradiol metabolism in HepG2 cells and primary culture pig hepatocytes and their effects on 17βHSD7 gene expression.

    PubMed

    Chen, Gang; Li, Sicong; Dong, Xinxing; Bai, Ying; Chen, Ailiang; Yang, Shuming; Fang, Meiying; Zamaratskaia, Galia; Doran, Olena

    2012-01-01

    Steroid metabolism is important in various species. The accumulation of androgen metabolite, androstenone, in pig adipose tissue is negatively associated with pork flavor, odour and makes the meat unfit for human consumption. The 17β-hydroxysteroid dehydrogenase type 7 (17βHSD7) expressed abundantly in porcine liver, and it was previously suggested to be associated with androstenone levels. Understanding the enzymes and metabolic pathways responsible for androstenone as well as other steroids metabolism is important for improving the meat quality. At the same time, metabolism of steroids is known to be species- and tissue-specific. Therefore it is important to investigate between-species variations in the hepatic steroid metabolism and to elucidate the role of 17βHSD7 in this process. Here we used an effective methodological approach, liquid chromatography coupled with mass spectrometry, to investigate species-specific metabolism of androstenone, testosterone and beta-estradiol in HepG2 cell line, and pig cultured hepatocytes. Species- and concentration-depended effect of steroids on 17βHSD7 gene expression was also investigated. It was demonstrated that the investigated steroids can regulate the 17βHSD7 gene expression in HepG2 and primary cultured porcine hepatocytes in a concentration-dependent and species-dependent pattern. Investigation of steroid metabolites demonstrated that androstenone formed a 3'-hydroxy compound 3β-hydroxy-5α-androst-16-ene. Testosterone was metabolized to 4-androstene-3,17-dione. Estrone was found as the metabolite for β-estradiol. Inhibition study with 17βHSD inhibitor apigenin showed that apigenin didn't affect androstenone metabolism. Apigenin at high concentration (50 µM) tends to inhibit testosterone metabolism but this inhibition effect was negligible. Beta-estradiol metabolism was notably inhibited with apigenin at high concentration. The study also established that the level of testosterone and β-estradiol metabolites

  1. Natural phenolic acids may increase serum estradiol level in ovariectomized rats.

    PubMed

    Zych, Maria; Folwarczna, Joanna; Trzeciak, Henryk I

    2009-01-01

    Natural phenolic acids are commonly present in plants consumed in the diet. Recently we have observed that different natural phenolic acids exert differential effects on the body mass gain in ovariectomized and non-ovariectomized female rats. The aim of the present study was to investigate the effects of ferulic, caffeic, p-coumaric and chlorogenic acids on serum estradiol and total cholesterol levels in ovariectomized and non-ovariectomized rats. The experiments were carried out on 3-month old female Wistar Cmd:(WI)WU rats, divided into following groups (n=8 in each group): non-ovariectomized control rats and non-ovariectomized rats receiving ferulic, caffeic, p-coumaric or chlorogenic acids, sham-operated control rats, ovariectomized control rats and ovariectomized rats receiving the same phenolic acids. The phenolic acids were administered at a dose of 10 mg/kg p.o. daily for 4 weeks. Serum estradiol and total cholesterol levels on the next day after the last administration of the phenolic acids were examined. The phenolic acids did not affect serum estradiol or total cholesterol levels in non-ovariectomized rats. In ovariectomized rats, caffeic acid and to a lesser extent p-coumaric acid increased serum estradiol level, which effect correlated with a decreased body mass gain. All the phenolic acids decreased serum cholesterol level in ovariectomized rats. Concluding, the anti-obesity activity of some phenolic acids may be, at least partially, connected with estrogenic pathways.

  2. Isolation and Bioaugmentation of an Estradiol-Degrading Bacterium and Its Integration into a Mature Biofilm▿

    PubMed Central

    Iasur-Kruh, Lilach; Hadar, Yitzhak; Minz, Dror

    2011-01-01

    Bioaugmentation can alter the potential activity as well as the composition of the naturally occurring microbial biota during bioremediation of a contaminated site. The focus of the current study is the pollutant 17β-estradiol (E2), which can cause endocrine effects and is potentially harmful to aquatic biota and to public health. The community composition and function of biofilms, originating from a wetland system, as affected by augmentation of an estradiol-degrading bacterium (EDB-LI1) under different conditions, were investigated. EDB-LI1 inoculation into biofilm from two wetland ponds representing early and advanced water treatment stages, respectively, yielded three significant observations, as follows: (i) EDB-LI1, enriched from a biofilm of a constructed wetland wastewater treatment system, was detected (by quantitative PCR [qPCR] analysis) in this environment in the augmented biofilm only; (ii) the augmented biofilm acquired the ability to remove estradiol; and (iii) the bacterial community composition (analyzed by PCR-denaturing gradient gel electrophoresis [DGGE]) of the augmented biofilm differed from that of the control biofilm. Furthermore, EDB-LI1 bioaugmentation showed a higher level of removal of estradiol with biofilms that originated from the advanced-treatment-stage wetland pond than those from the early-treatment-stage pond. Hence, the bioaugmentation efficiency of EDB-LI1 depends on both the quality of the feed water and the microbial community composition in the pond. PMID:21478310

  3. 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

  4. Rapid Effects of Estradiol on Aggression in Birds and Mice: The Fast and the Furious

    PubMed Central

    Heimovics, Sarah A.; Trainor, Brian C.; Soma, Kiran K.

    2015-01-01

    Across invertebrates and vertebrates, steroids are potent signaling molecules that affect nearly every cell in the organism, including cells of the nervous system. Historically, researchers have focused on the genomic (or “nuclear-initiated”) effects of steroids. However, all classes of steroids also have rapid non-genomic (or “membrane-initiated”) effects, although there is far less basic knowledge of these non-genomic effects. In particular, steroids synthesized in the brain (“neurosteroids”) have genomic and non-genomic effects on behavior. Here, we review evidence that estradiol has rapid effects on aggression, an important social behavior, and on intracellular signaling cascades in relevant regions of the brain. In particular, we focus on studies of song sparrows (Melospiza melodia) and Peromyscus mice, in which estradiol has rapid behavioral effects under short photoperiods only. Furthermore, in captive Peromyscus, estrogenic compounds (THF-diols) in corncob bedding profoundly alter the rapid effects of estradiol. Environmental factors in the laboratory, such as photoperiod, diet, and bedding, are critical variables to consider in experimental design. These studies are consistent with the hypothesis that locally-produced steroids are more likely than systemic steroids to act via non-genomic mechanisms. Furthermore, these studies illustrate the dynamic balance between genomic and non-genomic signaling for estradiol, which is likely to be relevant for other steroids, behaviors, and species. PMID:25980562

  5. Sex-hormone binding globulin from sheep serum: purification and effects of pregnancy and treatment with exogenous estradiol.

    PubMed

    Kouretas, D; Laliotis, V; Taitzoglou, I; Georgellis, A; Tsantarliotou, M; Mougios, V; Amiridis, G; Antonoglou, O

    1999-07-01

    Sex-hormone binding globulin (SHBG) is a protein that binds sex steroids in the serum of many species. SHBG binds androgens and estrogens in humans and primates with high affinity, but behaves as an androgen binding protein in other species. Here we purified SHBG from ewe and ram sera to homogeneity, by a simple and rapid method. The K(D) of the purified protein was found to be 3.63 nM for testosterone and around 600 nM for estradiol. We also studied the effect of pregnancy on SHBG levels in ewes and the effect of exogenous estradiol administration either orally or parenterally on SHBG levels in rams. Basal levels of SHBG in sheep are not affected by pregnancy or exposure to exogenous estradiol. It is concluded that SHBG regulation of expression in ewes and rams differs from that in humans in that it is not affected by estrogen and possibly is species specific.

  6. Identification, characterization of selenoprotein W and its mRNA expression patterns in response to somatostatin 14, cysteamine hydrochloride, 17β-estradiol and a binary mixture of 17β-estradiol and cysteamine hydrochloride in topmouth culter (Erythroculter ilishaeformis).

    PubMed

    Dong, Haiyan; Chen, Wenbo; Sun, Chao; Sun, Jianwei; Wang, Yanlin; Xie, Chao; Fu, Qianwen; Zhu, Junjie; Ye, Jinyun

    2017-02-01

    In this study, a selenoprotein W cDNA was cloned from topmouth culter (Erythroculter ilishaeformis), and it was designated as EISelW. The EISelW open reading frame was composed of 261 base pairs (bp), encoding 86-amino-acid protein. The 5' untranslated region (UTR) consisted of 104 bp, and the 3'-UTR was composed of 365 bp. A selenocysteine insertion sequence (SECIS) element was found in the 3'-UTR of EISelW mRNA. The SECIS element was classified as form II because of a small additional apical loop presented in SECIS element of EISelW mRNA. Bioinformatic approaches showed that the secondary structure of EISelW was a β1-α1-β2-β3-β4-α2 pattern from amino-terminal to carboxy-terminal. Real-time PCR analysis of EISelW mRNAs expression in 17 tissues showed that the EISelW mRNA was predominantly expressed in liver, ovary, pituitary, various regions of the brain, spinal cord and head kidney. Study of intraperitoneal injection showed that the levels of EISelW mRNA in brain, liver, ovary and spleen were regulated by somatostatin 14 (SS14), 17β-estradiol (E2), cysteamine hydrochloride (CSH) and a binary mixture of E2 and CSH, dependent on the dosage. These results suggest that E2, SS14 and CSH status may affect tissues of selenium metabolism by regulating the expression of SelW mRNA, as SelW plays a central role in selenium metabolism.

  7. Sex differences in episodic memory: minimal influence of estradiol.

    PubMed

    Yonker, Julie E; Eriksson, Elias; Nilsson, Lars Göran; Herlitz, Agneta

    2003-07-01

    Sex differences exist for several cognitive tasks and estrogen has been suggested to influence these differences. Eighteen men and 18 women were matched on age and estradiol level. Potential sex differences were assessed in episodic memory, semantic memory, verbal fluency, problem solving, and visuospatial ability. Significant sex differences, favoring women, were found for tasks assessing episodic memory. Correlations between estradiol level and cognitive performance were significant for face recognition in females. Since sex differences remained in verbal episodic memory tasks and face recognition despite matched levels of estradiol, circulating estradiol does not appear to be of paramount consequence for observed sex differences in episodic memory.

  8. The role of S-adenosyl methionine in preventing FOLFOX-induced liver toxicity: a retrospective analysis in patients affected by resected colorectal cancer treated with adjuvant FOLFOX regimen.

    PubMed

    Vincenzi, Bruno; Santini, Daniele; Frezza, Anna Maria; Berti, Pierpaolo; Vespasiani, Umberto; Picardi, Antonio; Tonini, Giuseppe

    2011-05-01

    Hepatic toxicity is often related to chemotherapy agent administration, and it represents one of the principal causes of dose reduction and chemotherapy delays or discontinuation. S-Adenosyl methionine (AdoMet) supplementation is effective in the treatment of a variety of liver injuries, but it has never been evaluated in the prevention of chemotherapy-induced liver damage. A total of 105 patients affected by resected colorectal cancer (CRC) were enrolled. Forty-five were treated with FOLFOX IV adjuvant regimen without administering AdoMet, 60 were treated with the same regimen plus supplementation with AdoMet. Liver enzyme levels were assessed before starting the treatment and every therapy cycle. Liver toxicity, chemotherapy course delays, discontinuations and dose reductions due to liver toxicity were recorded. Aspartate aminotransferase (AST) (p < 0.001), alanine transaminase (ALT) (p = 0.003), bilirubin (p = 0.04) and gamma-glutamyltransferase (γ-GT) (p = 0.002) median level at the end of adjuvant therapy were significantly lower in patients treated with Adome. Patients supplemented with AdoMet experimented a lower grade of liver toxicity (p = 0.002) and had a reduced need of course delay (p < 0.0001) and dose reduction (p = 0.031). The results of our study demonstrate a protective effect of AdoMet supplementation in patients affected by resected CRC treated with FOLFOX IV adjuvant regimen.

  9. Massive myeloid sarcoma affecting the central nervous system, mediastinum, retroperitoneum, liver, and rectum associated with acute myeloblastic leukaemia: a case report

    PubMed Central

    Best-Aguilera, C R; Vazquez-Del Mercado, M; Muñoz-Valle, J F; Herrera-Zarate, L; Navarro-Hernandez, R E; Martin-Marquez, B T; Oregon-Romero, E; Ruiz-Quezada, S; Bonilla, G M; Lomeli-Guerrero, A

    2005-01-01

    Myeloid sarcomas are extramedullary tumours with granulocytic precursors. When associated with acute myelogenous leukaemia (AML), these tumours usually affect no more than two different extramedullary regions. This report describes a myeloid sarcoma associated with AML with tumour formation at five anatomical sites. The patient was a 37 year old man admitted in September 1999 with a two month history of weight loss, symptoms of anaemia, rectal bleeding, and left facial nerve palsy. The anatomical sites affected were: the rectum, the right lobe of the liver, the mediastinum, the retroperitoneum, and the central nervous system. A bone marrow smear was compatible with AML M2. Flow cytometry showed that the peripheral blood was positive for CD4, CD11, CD13, CD14, CD33, CD45, and HLA-DR. A karyotypic study of the bone marrow revealed an 8;21 translocation. The presence of multiple solid tumours in AML is a rare event. Enhanced expression of cell adhesion molecules may be the reason why some patients develop myeloid sarcomas. PMID:15735171

  10. Lacking of estradiol reduces insulin exocytosis from pancreatic β-cells and increases hepatic insulin degradation.

    PubMed

    Santos, Roberta S; Batista, Thiago M; Camargo, Rafael L; Morato, Priscila N; Borck, Patrícia C; Leite, Nayara C; Kurauti, Mirian A; Wanschel, Amarylis C B A; Nadal, Ángel; Clegg, Deborah J; Carneiro, Everardo M

    2016-10-01

    Low levels of plasma estrogens are associated with weight-gain, android fat distribution, and a high prevalence of obesity-related comorbidities such as glucose intolerance and type II diabetes. The mechanisms underlying the association between low levels of estrogens and impaired glucose homeostasis are not completely understood. To begin to test this, we used three-month-old female C57BL/6J mice that either underwent ovariectomy (OVX) or received a sham surgery (Sham), and we characterized glucose homeostasis. In a subsequent series of experiments, OVX mice received estradiol treatment (OVX+E2) or vehicle (OVX) for 6 consecutive days. As has been previously reported, lack of ovarian hormones resulted in dysregulated glucose homeostasis. To begin to explore the mechanisms by which this occurs, we characterized the impact of estrogens on insulin secretion and degradation in these mice. Insulin secretion and plasma insulin levels were lower in OVX mice. OVX mice had lower levels of pancreatic Syntaxin 1-A (Synt-1A) protein, which is involved in insulin extrusion from the pancreas. In the liver, OVX mice had higher levels of insulin-degrading enzyme (IDE) and this was associated with higher insulin clearance. Estradiol treatment improved glucose intolerance in OVX mice and restored insulin secretion, as well as normalized the protein content of pancreatic Synt-1A. The addition of estrogens to OVX mice reduced IDE protein to that of Sham mice. Our data suggest loss of ovarian estradiol following OVX led to impaired glucose homeostasis due to pancreatic β-cell dysfunction in the exocytosis of insulin, and upregulation of hepatic IDE protein content resulting in lower insulinemia, which was normalized by estradiol replacement.

  11. 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…

  12. 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…

  13. Repeated Estradiol Treatment Attenuates Chronic Cerebral Hypoperfusion-Induced Neurodegeneration in Rat Hippocampus.

    PubMed

    Stanojlović, Miloš; Guševac, Ivana; Grković, Ivana; Mitrović, Nataša; Zlatković, Jelena; Horvat, Anica; Drakulić, Dunja

    2016-08-01

    Although a substantial number of pre-clinical and experimental studies have investigated effects of 17β-estradiol, its precise molecular mechanism of action in the early state of chronic cerebral hypoperfusion remains controversial. The present study attempted to verify whether post-ischemic estradiol treatment (33.3 μg/kg for seven consecutive days) affects previously reported number of hippocampal apoptotic cells and amount of DNA fragmentation characteristic for apoptosis as well as the expression of key elements within synaptosomal Akt and Erk signal transduction pathways (NF-κB, Bax, Bcl-2, cytochrome C, caspase 3, and PARP). Additionally, alterations of aforementioned molecules linked to protection in various neurodegenerative disorders were monitored in the cytosolic, mitochondrial, and nuclear fractions associating investigated kinases and NF-κB with gene expression of their downstream effectors-Bcl-2, Bax, and caspase 3. The results revealed that an initial increase in the number of apoptotic cells and amount of DNA fragmentation induced by chronic cerebral hypoperfusion was significantly reduced by 17β-estradiol. In synaptic regions, an altered profile with respect to the protein expression of Bcl-2 and phosphorylated Akt was detected, although the level of other examined proteins was not modified. In other investigated sub-cellular fractions, 17β-estradiol elicited phosphorylation and translocation of Akt and Erk along with modulation of the expression of their subsequent effectors. Our findings support the concept that repeated post-ischemic 17β-estradiol treatment attenuates neurodegeneration induced by chronic cerebral hypoperfusion in hippocampus through the activation of investigated kinases and regulation of their downstream molecules in sub-cellular manner indicating a time window and regime of its administration as a valid therapeutic intervention.

  14. Reproductive effects on freshwater fish exposed to 17α-trenbolone and 17α-estradiol.

    PubMed

    Robinson, Joseph A; Staveley, Jane P; Constantine, Lisa

    2017-03-01

    17α-Trenbolone and 17α-estradiol are principal metabolites in cattle excreta following the administration of Synovex(®) ONE, which contains trenbolone acetate and estradiol benzoate. As part of the environmental assessment of the use of Synovex(®) ONE, data were generated to characterize the effects of 17α-trenbolone and 17α-estradiol on the reproduction of freshwater fish. These substances are known endocrine disruptors, so the purpose of testing was not to clarify these properties but to identify concentrations representing population-relevant effects for use in risk characterization. The short-term reproduction assay was conducted with 17α-trenbolone using the fathead minnow (Pimephales promelas) and the medaka (Oryzias latipes) and with 17α-estradiol using the fathead minnow. Adverse effects on the population-relevant endpoints of survival and fecundity were used to establish the no-observed-effect concentration (NOEC) and the lowest-observed-effect concentration (LOEC) for each study. For 17α-trenbolone, adverse effects on fecundity of the fathead minnow occurred at 120 ng/L; this was the LOEC, and the NOEC was 35 ng/L. 17β-Trenbolone did not adversely affect survival and fecundity of medaka at the concentrations tested, resulting in a NOEC of 110 ng/L and a LOEC of >110 ng/L. 17α-Estradiol did not adversely impact survival and fecundity of the fathead minnow at the concentrations tested, resulting in a NOEC and LOEC of 250 ng/L and >250 ng/L, respectively. Environ Toxicol Chem 2017;36:636-644. © 2016 SETAC.

  15. Prolactin and Estradiol Profile in a Cohort of Colombian Women with Systemic Lupus Erythematosus.

    PubMed

    Aulestia, Carolina; De Zubiría, Alberto; Granados, Carlos; Suárez, Johanna; Cervera, Ricard

    2016-09-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease with multiorgan involvement and wide variability in presentation and course. Although it can appear at any age, women of childbearing age are primarily affected. This has led to the proposal of a hormonal role in the development of SLE. Among the main hormones shown to have immunomodulatory effects are estradiol, progesterone and prolactin. To report the levels of estradiol and prolactin in SLE patients and establish the relationship between these levels and disease activity, and to determine whether the phases of the menstrual cycle influence the activity of SLE and its relationship to hormone levels. In this cross-sectional study, we examined 60 women with SLE. We measured disease activity using SLEDAI and BILAG. We obtained peripheral blood samples to determine the levels of estradiol, progesterone, and prolactin. Patients' age ranged between 16 and 65 years and the mean disease duration was 5.5 years (0-20). SLE was active (SLEDAI > 6) in 13 patients and inactive in 47. Thirty patients were in a pre-ovulatory menstrual cycle phase, 13 in a post-ovulatory cycle, and 17 were menopausal. We found a significant association between C4 levels and disease activity (P = 0.01) and between estradiol levels and disease activity in the kidney (P = 0.04). We did not find hyperprolactinemia in any patient. In this population, we found an association between estradiol levels and organ-specific activity in the kidney. One may speculate as to whether our population might benefit from the implementation of anti-estrogen therapy for control of disease activity, particularly in the kidney.

  16. Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers.

    PubMed

    Robertson, Philmore; Hellriegel, Edward T; Arora, Sanjay; Nelson, Michael

    2002-01-01

    Modafinil has been reported to produce a concentration-related induction of CYP3A4/5 activity in vitro in primary cultures of human hepatocytes. Our objective was to determine whether the pharmacokinetics of steady-state ethinyl estradiol (INN, ethinylestradiol) and single-dose triazolam were altered after 4 weeks of modafinil treatment in volunteers. This was a placebo-controlled, single-blind, single-period study in 41 female subjects who were receiving long-term treatment with an oral contraceptive that contained ethinyl estradiol (0.035 mg) and norgestimate (0.180-0.250 mg). Pharmacokinetic profiles for ethinyl estradiol and for a single oral dose of triazolam (0.125 mg) were obtained the day before initiation of treatment with modafinil (200 mg for 7 days, followed by 400 mg for 21 days) or placebo (28 days). A second dose of triazolam was administered with the final dose of modafinil, and pharmacokinetic profiling was repeated. The modafinil treatment group had a marked decrease in maximum observed plasma concentrations and areas under the plasma concentration-time curve for triazolam relative to placebo, with a much smaller decrease in these parameters for ethinyl estradiol. The half-life of triazolam was also decreased, but the half-life of ethinyl estradiol did not appear to be affected by treatment with modafinil. Modafinil induced CYP3A4/5 activity in humans in vivo, suggesting that there is potential for metabolic drug-drug interactions between modafinil and substrates of CYP3A4/5. However, the induction appeared to be more gastrointestinal than hepatic in nature. Therefore significant metabolic drug-drug interactions are most likely to occur with compounds (such as triazolam) that undergo significant gastrointestinal CYP3A4/5-mediated first-pass metabolism.

  17. 17Beta-Estradiol Inhibits Calcium-Activated Potassium Channel Expressions in Rat Whole Bladder

    PubMed Central

    2016-01-01

    Purpose: To investigate the effect of estrogen on the expression of calcium-activated potassium (KCa) channels in an overactive bladder rat model. To this end, mRNA and protein levels of KCa channel subtypes in the bladder of ovariectomized rats were measured by reverse transcription polymerase chain reaction and western blotting, respectively. Methods: Ten-week-old female Sprague-Dawley rats were divided randomly into 3 groups: sham-operated control group (n=11), ovariectomy group (n=11), and the group treated with estrogen after ovariectomy (n=12). Rats in the last group were subcutaneously injected with 17β-estradiol (50 μg/kg) every other day for 2 weeks, whereas rats in the other 2 groups received vehicle (soybean oil) alone. Two weeks after treatment, the whole bladder was excised for mRNA and protein measurements. Results: Protein levels of the large-conductance KCa (BK) channels in the ovariectomy group were 1.5 folds higher than those in the sham-operated control group. However, the protein levels of the other KCa channel subtypes did not change significantly upon bilateral ovariectomy. Treatment with 17β-estradiol after ovariectomy restored BK channel protein levels to the control value. In contrast, BK channel mRNA levels were not significantly affected by either ovariectomy alone or 17β-estradiol treatment. The small-conductance KCa type 3 channel (SK3) mRNA and protein levels decreased to 75% of control levels upon 17β-estradiol treatment. Conclusions: These results suggest that 17β-estradiol may influence urinary bladder function by modulating BK and SK3 channel expression. PMID:27032553

  18. Saline-linked surface radiofrequency ablation: factors affecting steam popping and depth of injury in the pig liver.

    PubMed

    Topp, Stefan A; McClurken, Michael; Lipson, David; Upadhya, Gundumi A; Ritter, Jon H; Linehan, David; Strasberg, Steven M

    2004-04-01

    Saline-linked surface radiofrequency (RF) ablation is a new technique for applying RF energy to surfaces. The surface is cooled, which prevents charring and results in deeper coagulation. However, subsurface heating may lead to steam formation and a form of tissue disruption called steam popping. We determined parameters that predict steam popping and depth of tissue destruction under nonpopping conditions. A commercially available saline-linked surface RF cautery device (Floating Ball 3.0, TissueLink, Inc.) was used. One hundred eighty circular lesions were created varying in lesion diameter, duration, power, and inflow occlusion. Variables affecting popping were determined. Then factors influencing lesion depth were studied at fixed nonpopping diameter/power combinations (1 cm/10W, 2 cm/15W, 4 cm/60W). Tissue viability was determined in selected samples by staining of tissue NADH. The probability of steam popping was directly related to power level and inflow occlusion, and indirectly related to lesion diameter. Depth of injury under safe nonpopping conditions was directly related to power, lesion size, and inflow occlusion. Maximum depth in excess of 20 mm was achieved using a 4 cm diameter at 60W with inflow occlusion. Microscopy of NADH-stained tissues showed a complete cell killing in the macroscopically visible coagulated area. Steam popping can be avoided by selecting power level/lesion diameter combinations. Tissue destruction to 20 mm can be safely achieved with short periods of inflow occlusion. The device has promise as a treatment of superficial tumors and close resection margins.

  19. Dehydroepiandrosterone affects the expression of multiple genes in rat liver including 11 beta-hydroxysteroid dehydrogenase type 1: a cDNA array analysis.

    PubMed

    Gu, Shi; Ripp, Sharon L; Prough, Russell A; Geoghegan, Thomas E

    2003-03-01

    Dehydroepiandrosterone (DHEA) is a C-19 adrenal steroid precursor to the gonadal steroids. In humans, circulating levels of DHEA, as its sulfated conjugate, are high at puberty and throughout early adulthood but decline with age. Dietary supplementation to maintain high levels of DHEA purportedly has beneficial effects on cognitive memory, the immune system, and fat and carbohydrate metabolism. In rodents, DHEA is a peroxisome proliferator that induces genes for the classical peroxisomal and microsomal enzymes associated with this response. These effects are mediated through activation of peroxisome proliferator-activated receptor alpha (PPAR alpha). However, DHEA can affect the expression of genes independently of PPAR alpha, including the gene for the major inducible drug and xenobiotic metabolizing enzyme, cytochrome P450 3A23. To elucidate the biochemistry associated with DHEA treatment, we employed a cDNA gene expression array using liver RNA from rats treated with DHEA or the classic peroxisome proliferator nafenopin. Principal components analysis identified 30 to 35 genes whose expression was affected by DHEA and/or nafenopin. Some were genes previously identified as PPAR-responsive genes. Changes in expression of several affected genes were verified by quantitative reverse transcriptase-polymerase chain reaction. These included aquaporin 3, which was induced by DHEA and to a lesser extent nafenopin, nuclear tyrosine phosphatase, which was induced by both agents, and 11 beta-hydroxysteroid dehydrogenase 1, which was decreased by treatment with DHEA in a dose-dependent fashion. Regulation of 11 beta-hydroxysteroid dehydrogenase 1 expression is important since the enzyme is believed to amplify local glucocorticoid signaling, and its repression may cause some of the metabolic effects associated with DHEA.

  20. Estradiol and hemodynamics during ovulation induction.

    PubMed

    Veille, J C; Morton, M J; Burry, K; Nemeth, M; Speroff, L

    1986-09-01

    Left ventricular size and stroke volume increase in human pregnancy and during estrogen administration in laboratory animals. In order to determine if elevated levels of endogenous estrogens in humans produce hemodynamic changes similar to those that occur during pregnancy, 14 patients were studied during ovulation induction at day 8 +/- 2 (SD) (proliferative phase) and at day 14 +/- 4 (midcycle) of their cycles. M-mode echocardiography was carried out with the patient in the left lateral decubitus, head down and head up positions. The mean serum estradiol level was 294 +/- 234 (SD) pg ml-1 at day 8 +/- 2 (treatment day) and it increased to 1503 +/- 531 pg ml-1 at day 14 +/- 4 (cycle day) of the same cycle. This change in serum estradiol was significant (P less than 0.001), associated with an increase in left ventricle diastolic dimension of 2.3 +/- 1.1 mm (P less than 0.001). During the same time period stroke volume and cardiac index correspondingly increased. Heart rate, fractional shortening, and blood pressure did not change and systemic vascular resistance decreased. Many of the cardiovascular adaptations of pregnancy are duplicated by high levels of endogenous estrogens and these changes are evident in as few as 6 days. Thus, we conclude that changes in endogenous estrogen correlate with certain cardiovascular parameters, the most striking of which is the left ventricular size. This may be one of the adaptive mechanisms by which the maternal circulation adapts to pregnancy.

  1. Pure crystalline estradiol pellet implantation for contraception.

    PubMed

    Asch, R H; Greenblatt, R B; Mahesh, V B

    1978-01-01

    The subcutaneous implantation of estradiol pellets was found to be a simple and effective contraceptive method with good patient acceptance and minimal untoward effects. The pellets (25 mg each) were implanted through a Kearn's trocar into the abdominal wall, 2.5 to 5 cm above and parallel to Poupart's ligament. The regimen began with four pellets, and the dose was maintained or decreased by one pellet every 6 months (four, three, two, one). A potent progestogen was utilized monthly for induction of withdrawal bleeding. Altogether, 236 patients were followed for a total of 1,060 courses in 6,360 cycles (489,02 woman-years). Two pregnancies occurred during therapy. Pearl's index was 0.37. No significant alterations occurred in body weight and blood pressure. Glucose tolerance test, standard blood profiles, and Papanicolaou smears were normal during therapy. No cases of thrombophlebitis, blurred vision, headaches, gastric symptoms, or amenorrhea-galactorrhea were observed. The suppression of ovulation was confirmed by endometrial biopsies, basal body temperature, and serum follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in a selected group of patients.

  2. Fat-soluble 17 beta-estradiol: a way of reducing dosage in steroid hormonal substitution?

    PubMed

    Schubert, W; Cullberg, G

    1988-01-01

    Eight ovariectomized women were given 0.5 mg 17 beta-estradiol cyclo-octyl acetate (E2COA) dissolved in arachis oil + 0.15 mg desogestrel, and 2 mg micronized 17 beta-estradiol (mE2) + 0.15 mg desogestrel orally in a crossover fashion for 20 days each. The preparations were taken on 10 days together with a meal, on 10 days 3 hours after a meal. Blood samplings were performed 3 h after capsule ingestion for analysis of serum estradiol (S-E2), estrone (S-E1) and sex hormone binding globulin (SHBG). Before treatment, all women had climacteric complaints. During treatment these symptoms were alleviated and no discomfort was reported. No differences in serum levels of estrogens were found in either of the preparations when capsules were taken with or without food. However, serum levels of E2 were found to be 100% higher per mg substance given after E2COA vis-à-vis mE2. This indicates either a delayed breakdown and/or a better resorption. The E1/E2 ratio after E2COA was only half that after mE2 intake. This hints at another route of resorption. SHBG concentrations were somewhat elevated following mE2 administration, whereas a slight decrease was found after E2COA. The resulting post-treatment difference was significant, suggesting a less estrogenic liver effect by E2COA. No accumulation of E2 or E1 was seen after either of the preparations. Our findings support the hypothesis that E2COA, being fat soluble, is resorbed via the lymphatic system. By avoiding the first liver pass the dosage of estrogen can be halved.

  3. 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.

  4. 21 CFR 522.2477 - Trenbolone acetate and estradiol.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... acetate and 4 mg estradiol, and 1 pellet containing 29 mg tylosin tartrate) per implant dose. (C) 200 mg... containing 29 mg tylosin tartrate) per implant dose. (F) 80 mg trenbolone acetate and 16 mg estradiol (one..., and 1 pellet containing 29 mg tylosin tartrate) per implant dose. (G) 200 milligram (mg) trenbolone...

  5. 21 CFR 522.2477 - Trenbolone acetate and estradiol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... acetate and 4 mg estradiol, and 1 pellet containing 29 mg tylosin tartrate) per implant dose. (C) 200 mg... containing 29 mg tylosin tartrate) per implant dose. (F) 80 mg trenbolone acetate and 16 mg estradiol (one..., and 1 pellet containing 29 mg tylosin tartrate) per implant dose. (G) 200 milligram (mg) trenbolone...

  6. 21 CFR 522.2477 - Trenbolone acetate and estradiol.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... acetate and 4 mg estradiol, and 1 pellet containing 29 mg tylosin tartrate) per implant dose. (C) 200 mg... containing 29 mg tylosin tartrate) per implant dose. (F) 80 mg trenbolone acetate and 16 mg estradiol (one..., and 1 pellet containing 29 mg tylosin tartrate) per implant dose. (G) 200 milligram (mg) trenbolone...

  7. Long-acting estrogenic responses of estradiol fatty acid esters.

    PubMed

    Vazquez-Alcantara, M A; Menjivar, M; Garcia, G A; Díaz-Zagoya, J C; Garza-Flores, J

    1989-12-01

    Estradiol esters at C-17 and C-3 with palmitic, stearic and oleic acids were chemically synthesized and then evaluated for their long-acting estrogenic responses in ovariectomized rats. The duration of the biological effects was measured after a single subcutaneous dose of 0.1 mumol of each ester and compared with those observed with 17 beta-estradiol, estradiol 3-benzoate and estradiol 17-enanthate. Vaginal citology, uterophyc action, serum gonadotropins inhibition and 17 beta-estradiol levels were measured 0, 5, 10, 20, 30 and 60 days after injection. The results disclosed that most of the estradiol derivatives evaluated exhibited a long-acting estrogenic action. However, the monoesters at C-17 showed longer effects that monoesters at C-3, while the estradiol diesters exhibited the shortest effects. In addition as shown by its low serum levels, all estradiol esters with unsaturated fatty acids show a decreased E2 absorption. The overall results indicated that esterification of E2 with long chain fatty acids provided long-acting properties to it, being higher with C-17 esters. Whether some of these compounds could be employed in substitutive endocrine therapy remains to be established.

  8. Dissipation of 17B-estradiol in composted poultry litter

    USDA-ARS?s Scientific Manuscript database

    The effects of heated composting and ambient temperature poultry waste decomposition on the fate of 17ß-estradiol and testosterone were determined in separate experiments. A mixture of poultry litter, wood chips and straw was amended with [14C]17ß-estradiol or [14C]testosterone and allowed to under...

  9. THE DEVELOPMENT OF FEMALE SEXUAL BEHAVIOR REQUIRES PREPUBERTAL ESTRADIOL

    PubMed Central

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

    2011-01-01

    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 knockout (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 days P15–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–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. PMID:21490197

  10. Sex reversal by estradiol in three reptilian orders.

    PubMed

    Bull, J J; Gutzke, W H; Crews, D

    1988-06-01

    Administration of exogenous estradiol caused embryos to develop ovaries rather than testes in alligators, softshell turtles, and leopard geckos. Alligators and leopard geckos are known to have environmental sex determination; softshell turtles lack both environmental sex determination and heteromorphic sex chromosomes. Sensitivity to gonadal feminization by estradiol thus appears to be widespread in amniotes.

  11. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... consists of: (1) 8 pellets, each pellet containing 25 milligrams (mg) trenbolone acetate and 3.5 mg estradiol benzoate. (2) 4 pellets, each pellet containing 25 mg trenbolone acetate and 3.5 mg estradiol...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone...

  12. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... consists of: (1) 8 pellets, each pellet containing 25 milligrams (mg) trenbolone acetate and 3.5 mg estradiol benzoate. (2) 4 pellets, each pellet containing 25 mg trenbolone acetate and 3.5 mg estradiol...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone...

  13. Factors affecting the enterohepatic circulation of oral contraceptive steroids.

    PubMed

    Orme, M L; Back, D J

    1990-12-01

    Oral contraceptive steroids may undergo enterohepatic circulation, but it is relevant for only estrogens, because these compounds can be directly conjugated in the liver. Animal studies show convincing evidence of the importance of the enterohepatic circulation, but studies in humans are much less convincing. The importance of the route and the rate of metabolism of ethinyl estradiol are reviewed. Some antibiotics have been reported anecdotally to reduce the efficacy of oral contraceptive steroids, but controlled studies have not confirmed this observation. Although gut flora are altered by oral antibiotics, the blood levels of ethinyl estradiol are not reduced, and one antibiotic at least (cotrimoxazole) enhances the activity of ethinyl estradiol.

  14. Estetrol is a weak estrogen antagonizing estradiol-dependent mammary gland proliferation.

    PubMed

    Gérard, C; Blacher, S; Communal, L; Courtin, A; Tskitishvili, E; Mestdagt, M; Munaut, C; Noel, A; Gompel, A; Péqueux, C; Foidart, J M

    2015-01-01

    Estetrol (E4) is a natural estrogen produced exclusively by the human fetal liver during pregnancy. Its physiological activity remains unknown. In contrast to ethinyl estradiol and estradiol (E2), E4 has a minimal impact on liver cell activity and could provide a better safety profile in contraception or hormone therapy. The aim of this study was to delineate if E4 exhibits an activity profile distinct from that of E2 on mammary gland. Compared with E2, E4 acted as a low-affinity estrogen in both human in vitro and murine in vivo models. E4 was 100 times less potent than E2 to stimulate the proliferation of human breast epithelial (HBE) cells and murine mammary gland in vitro and in vivo respectively. This effect was prevented by fulvestrant and tamoxifen, supporting the notion that ERα (ESR1) is the main mediator of the estrogenic effect of E4 on the breast. Interestingly, when E4 was administered along with E2, it significantly antagonized the strong stimulatory effect of E2 on HBE cell proliferation and on the growth of mammary ducts. This study characterizes for the first time the impact of E4 on mammary gland. Our results highlight that E4 is less potent than E2 and exhibits antagonistic properties toward the proliferative effect of E2 on breast epithelial cells. These data support E4 as a potential new estrogen for clinical use with a reduced impact on breast proliferation.

  15. Detection of 17 β-Estradiol in Environmental Samples and for Health Care Using a Single-Use, Cost-Effective Biosensor Based on Differential Pulse Voltammetry (DPV).

    PubMed

    Dai, Yifan; Liu, Chung Chiun

    2017-03-29

    Environmental estrogen pollution and estrogen effects on the female reproductive system are well recognized scientifically. Among the estrogens, 17 β-estradiol is a priority in environmental estrogen pollution, and it is also a major contributor to estrogen which regulates the female reproductive system. 17 β-estradiol is carcinogenic and has a tumor promotion effect relating to breast cancer, lung cancer and others. It also affects psychological well-being such as depression, fatigue and others. Thus, a simple method of detecting 17 β-estradiol will be important for both environmental estrogen pollution and health care. This study demonstrates a single-use, cost-effective 17 β-estradiol biosensor system which can be used for both environmental and health care applications. The bio-recognition mechanism is based on the influence of the redox couple, K₃Fe(CN)₆/K₄Fe(CN)₆ by the interaction between 17 β-estradiol antigen and its α-receptor (ER-α; α-estrogen antibody). The transduction mechanism is an electrochemical analytical technique, differential pulse voltammetry (DPV). The levels of 17 β-estradiol antigen studied were between 2.25 pg/mL and 2250 pg/mL; Phosphate buffered saline (PBS), tap water from the Cleveland regional water district, and simulated urine were used as the test media covering the potential application areas for 17 β-estradiol detection. An interference study by testosterone, which has a similar chemical structure and molecular weight as those of 17 β-estradiol, was carried out, and this 17 β-estradiol biosensor showed excellent specificity without any interference by similar chemicals.

  16. [Membrane-bound sialoglycoproteins of the rat liver as affected by the combined action of benz(a)pyrene and sulfur dioxide].

    PubMed

    Merkur'eva, R V; Bushinskaia, L I; Skvortsova, N I; Dolinskaia, S I; Shaternikova, I S

    1981-01-01

    Simultaneous effect of benz(a)pyrene and sulphurous gas was accompanied by distinct alteration in metabolism of sialoglycoproteins in liver tissue; at the time N-acetylneuraminic acid was redistributed in liver subcellular organelles (mitochondria, lysosomes and endoplasmic reticulum) as well as cytochromes P-450 and b5 were induced in liver microsomes. The alterations observed appear to play a definite role in manifestation of the unfavourable effect in combined action of the carcinogen and chemical contaminations of environments.

  17. Waist-to-Hip Ratio, but Not Body Mass Index, Is Associated with Testosterone and Estradiol Concentrations in Young Women.

    PubMed

    Mondragón-Ceballos, Ricardo; García Granados, Mónica Dafne; Cerda-Molina, Ana Lilia; Chavira-Ramírez, Roberto; Hernández-López, Leonor Estela

    2015-01-01

    We studied if testosterone and estradiol concentrations are associated with specific female waist-to-hip ratios (WHRs) and body mass indices (BMIs). Participants were 187 young women from which waist, hips, weight, and height were measured. In addition, participants informed on which day of their menstrual cycle they were and provided a 6 mL saliva sample. Ninety-one of them were in the follicular phase and 96 in the luteal phase. Only in the fertile phase of the menstrual cycle we found a significant interaction between testosterone and estradiol affecting WHR (b ± s.e. = -0.000003 ± 0.000001;  t 94 = -2.12, adjusted R (2) = -0.008,  P = 0.03). Women with the highest levels of both hormones had the lowest WHRs, while women with low estradiol and high testosterone showed the highest WHRs. BMI significantly increased as testosterone increased in female in their nonfertile days.

  18. 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...

  19. 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...

  20. Effects of exposure to estradiol and estradiol plus testosterone on the Mongolian gerbil (Meriones unguiculatus) female prostate.

    PubMed

    Da Silva, Diego Augusto Lopes; Zanatelli, Marianna; Shinohara, Filipe Zardini; Góes, Rejane Maira; Dos Santos, Fernanda Cristina Alcântara; Vilamaior, Patricia Simone Leite; Taboga, Sebastião Roberto

    2013-05-01

    The female prostate is a differentiated organ found in several mammal species, including humans and rodents. This gland has been related to important functions on female reproductive biology. Although the factors, which regulate prostate's development and activity are not well known, its functionality has been related to steroid hormones. It is well established that cyclic changes of estradiol and progesterone levels promote histophysiological adaptations of the whole female body. In contrast, only a few is found about those adaptations in female prostate. Thus, this study aimed to evaluate the effect of estradiol and estradiol + testosterone association on gerbil female prostate in order to verify, which hormonal associations are necessary to its homeostasis. For this, adult females had the ovaries surgically removed. After recovering, they received estradiol and estradiol + testosterone doses through 30 days, each 48 h. The prostatic tissue underwent morphological and morphometric-estereological analysis. Hormonal restriction caused great gland involution and decreased secretory activity, aspects that were reverted by exposure to estradiol and estradiol + testosterone. However, these hormones were not able to re-establish the normal prostate histoarchitecture. The immunoreaction of steroid receptors (ER-α, ER-β, and AR) responded differently among the experimental and control groups, and PCNA assay showed a decrease in epithelial cell proliferation within groups that had hormone privation. Therefore, we conclude that estradiol and testosterone are able to influence prostate morphophysiology and the maintenance of gland homeostasis depends on a balance among these and other hormones. Copyright © 2013 Wiley Periodicals, Inc.

  1. Short-Term and Sub-Chronic Dietary Exposure to Aspalathin-Enriched Green Rooibos (Aspalathus linearis) Extract Affects Rat Liver Function and Antioxidant Status.

    PubMed

    van der Merwe, Johanna Debora; de Beer, Dalene; Joubert, Elizabeth; Gelderblom, Wentzel C A

    2015-12-18

    An aspalathin-enriched green rooibos (Aspalathus linearis) extract (GRE) was fed to male Fischer rats in two independent studies for 28 and 90 days. The average dietary total polyphenol (TP) intake was 756 and 627 mg Gallic acid equivalents (GAE)/kg body weight (bw)/day over 28 and 90 days, respectively, equaling human equivalent doses (HEDs) of 123 and 102 GAE mg/kg bw/day. Aspalathin intake of 295 mg/kg bw/day represents a HED of 48 mg/kg bw/day (90 day study). Consumption of GRE increased feed intake significantly (p < 0.05) compared to the control after 90 days, but no effect on body and organ weight parameters was observed. GRE significantly (p < 0.05) reduced serum total cholesterol and iron levels, whilst significantly (p < 0.05) increasing alkaline phosphatase enzyme activity after 90 days. Endogenous antioxidant enzyme activity in the liver, i.e., catalase and superoxide dismutase activity, was not adversely affected. Glutathione reductase activity significantly (p < 0.05) increased after 28 days, while glutathione (GSH) content was decreased after 90 days, suggesting an altered glutathione redox cycle. Quantitative Real Time polymerase chain reaction (PCR) analysis showed altered expression of certain antioxidant defense and oxidative stress related genes, indicative, among others, of an underlying oxidative stress related to changes in the GSH redox pathway and possible biliary dysfunction.

  2. Exposure to a commercial glyphosate formulation (Roundup®) alters normal gill and liver histology and affects male sexual activity of Jenynsia multidentata (Anablepidae, Cyprinodontiformes).

    PubMed

    Hued, Andrea Cecilia; Oberhofer, Sabrina; de los Ángeles Bistoni, María

    2012-01-01

    Roundup is the most popular commercial glyphosate formulation applied in the cultivation of genetically modified glyphosate-resistant crops. The aim of this study was to evaluate the histological lesions of the neotropical native fish, Jenynsia multidentata, in response to acute and subchronic exposure to Roundup and to determine if subchronic exposure to the herbicide causes changes in male sexual activity of individuals exposed to a sublethal concentration (0.5 mg/l) for 7 and 28 days. The estimated 96-h LC50 was 19.02 mg/l for both male and female fish. Gill and liver histological lesions were evaluated through histopathological indices allowing quantification of the histological damages in fish exposed to different concentrations of the herbicide. Roundup induced different histological alterations in a concentration-dependent manner. In subchronic-exposure tests, Roundup also altered normal histology of the studied organs and caused a significant decrease in the number of copulations and mating success in male fish exposed to the herbicide. It is expected that in natural environments contaminated with Roundup, both general health condition and reproductive success of J. multidenatata could be seriously affected.

  3. Augmenter of liver regeneration, a protective factor against ROS-induced oxidative damage in muscle tissue of mitochondrial myopathy affected patients.

    PubMed

    Polimeno, Lorenzo; Rossi, Roberta; Mastrodonato, Maria; Montagnani, Monica; Piscitelli, Domenico; Pesetti, Barbara; De Benedictis, Leonarda; Girardi, Bruna; Resta, Leonardo; Napoli, Anna; Francavilla, Antonio

    2013-11-01

    Mitochondria-related myopathies (MM) are a group of different diseases defined by a varying degree of dysfunctions of the mitochondrial respiratory chain which leads to reactive oxygen species (ROS) generation followed by oxidative stress and cellular damage. In mitochondrial myopathy muscle tissue an overexpression of antioxidant enzymes has been documented probably as an attempt to counteract the free radical generation. We previously documented, in human non-pathological muscle fibres, the expression of the augmenter of liver regeneration (ALR), a sulfhydryl oxidase enzyme, whose presence is related to the mitochondria; indeed it has been demonstrated that ALR mainly localizes in the mitochondrial inter-membrane space. Furthermore we reported, in different experimental models, in vivo and in vitro, the anti-apoptotic and anti-oxidative capacities of ALR, achieved by up-regulating Bcl-2 anti-apoptotic family factors and the anti-apoptotic/anti-oxidative secretory isoform of clusterin (sClu). With the present study we aimed to determine ALR, Bcl-2 protein, clusterin and ROS expression in muscle tissue biopsies from MM-affected patients. Non-pathological muscle tissue was used as control. Enzymatic, histochemical, immunohistochemical and immune electron microscopy techniques were performed. The data obtained revealed in MM-derived muscle tissue, compared to non-pathological tissue, the over-expression of ROS, ALR and Bcl-2 and the induction of the nuclear, pro-apoptotic, isoform of clusterin (nCLU).

  4. Pregnancy and liver disease.

    PubMed

    Westbrook, Rachel H; Dusheiko, Geoffrey; Williamson, Catherine

    2016-04-01

    Pregnancy associated liver diseases affect up to 3% of pregnant women and are the most frequent cause of liver dysfunction in pregnancy. When severe, they are associated with significant morbidity and mortality for both mother and infant. A rapid evaluation to distinguish them from non-pregnancy related liver dysfunction is essential, in order to facilitate appropriate management. Liver disease unrelated to pregnancy can present de novo in pregnancy, or pregnancy can occur in women with preexisting liver pathology (Table 1). Research and subsequent advances in medical care have resulted in improved but still not satisfactory maternal and fetal outcomes. In this review we provide an overview of the liver diseases specific to the pregnant state and an update on their pathogenesis, treatment and outcomes. The risks of pregnancy in women with pre-existent liver pathology is detailed and recent advances in our understanding of specific risks and outcomes are discussed.

  5. Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment.

    PubMed

    Stanczyk, Frank Z; Archer, David F; Bhavnani, Bhagu R

    2013-06-01

    The need to seek improved combined oral contraceptive (COC) efficacy, with fewer health risks and better acceptability, has been ongoing since the introduction of COCs more than 50 years ago. New progestin formulations combined with lower doses of ethinyl estradiol (EE), the predominant estrogenic component of COCs, have reduced the incidence of venous thromboembolism and other negative outcomes of COC treatment. Previous attempts to use endogenous 17β-estradiol (E₂) instead of EE were limited primarily by poor cycle control. The recent introduction of E₂-based formulations has renewed interest to determine if there are potential benefits of using E₂ in COCs. These formulations have been shown to have similar efficacy and cycle control as EE-based COCs. This review provides a brief summary of the pharmacology of EE and E₂, including metabolism, pharmacokinetics and pharmacodynamics, as well as adverse effects of these estrogens.

  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. Bisphenol A and Estradiol are Equipotent in Antagonizing Cisplatin-Induced Cytotoxicity in Breast Cancer Cells

    PubMed Central

    LaPensee, Elizabeth W.; LaPensee, Christopher R.; Fox, Sejal; Schwemberger, Sandy; Afton, Scott; Ben-Jonathan, Nira

    2010-01-01

    Resistance to chemotherapy is a major problem facing breast cancer patients. Cisplatin, a highly effective DNA-damaging drug, has shown only little success in breast cancer treatment. We are reporting that low nanomolar doses of bisphenol A (BPA) or estradiol antagonize cisplatin cytotoxicity in breast cancer cells, with their effects not mediated via classical estrogen receptors. Although both compounds increase the expression of Bcl-2, a Bcl-2 inhibitor completely blocked the protective effects of BPA while only partially affecting those of estradiol. Blockade of BPA and E2 actions should sensitize ER-negative breast tumors to anti-cancer drugs and allow for the inclusion of cisplatin in treatment regimens. PMID:19796866

  8. Progesterone After Estradiol Modulates Shuttle-Cage Escape by Facilitating Volition

    PubMed Central

    Mayeaux, Darryl J.; Tandle, Sarah M.; Cilano, Sean M.; Fitzharris, Matthew J.

    2015-01-01

    In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized female rats to examine their performance in shuttle-cage escape learning without intentionally inducing a depressive-like state. Progesterone, not estradiol, within four hours of testing affected latencies to escape. The improvement produced by progesterone was in the decision to act, not in the speed of learning or speed of escaping. This parallels depression in humans in that depressed people are slower in volition, in their decisions to take action. PMID:26823653

  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.

  10. Diabetes mellitus may affect the long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after liver transplantation

    PubMed Central

    Zhang, Qing; Deng, Yong-Lin; Liu, Chang; Huang, Li-Hong; Shang, Lei; Chen, Xin-Guo; Wang, Le-Tian; Du, Jin-Zan; Wang, Ying; Wang, Pei-Xiao; Zhang, Hui; Shen, Zhong-Yang

    2016-01-01

    AIM To determine whether diabetes mellitus (DM) affects prognosis/recurrence after liver transplantation (LT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent LT with antiviral prophylaxis. Patient data were obtained from the China Liver Transplant Registry (https://www.cltr.org/). To compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis. RESULTS Univariate analysis of 1631 patients who underwent LT found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after LT between the two groups were significant (P = 0.041), but recurrence-free survival rates were not (P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years (P = 0.002), the presence of vascular invasion (P = 0.096), tumors ≤ 3 cm (P = 0.047), two to three tumor nodules (P = 0.007), Child-Pugh grade B (P = 0.018), and pre-LT alanine aminotransferase levels between 40 and 80 IU/L (P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/mL (P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM (P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after LT. CONCLUSION HBV-related HCC patients with DM have decreased long-term overall survival and poor LT outcomes. Prevention strategies for HCC patients with DM are recommended. PMID:27920478

  11. 2-Methoxyestradiol, an endogenous 17β-estradiol metabolite, inhibits microglial proliferation and activation via an estrogen receptor-independent mechanism.

    PubMed

    Schaufelberger, Sara A; Rosselli, Marinella; Barchiesi, Federica; Gillespie, Delbert G; Jackson, Edwin K; Dubey, Raghvendra K

    2016-03-01

    17β-Estradiol (estradiol) inhibits microglia proliferation. 2-Methoxyestradiol (2-ME) is an endogenous metabolite of estradiol with little affinity for estrogen receptors (ERs). We hypothesize that 2-ME inhibits microglial proliferation and activation and contributes to estradiol's inhibitory effects on microglia. We compared the effects of estradiol, 2-hydroxyestradiol [2-OE; estradiol metabolite produced by cytochrome P450 (CYP450)], and 2-ME [formed by catechol-O-methyltransferase (COMT) acting upon 2-OE] on microglial (BV2 cells) DNA synthesis, cell proliferation, activation, and phagocytosis. 2-ME and 2-OE were approximately three- and 10-fold, respectively, more potent than estradiol in inhibiting microglia DNA synthesis. The antimitogenic effects of estradiol were reduced by pharmacological inhibitors of CYP450 and COMT. Inhibition of COMT blocked the conversion of 2-OE to 2-ME and the antimitogenic effects of 2-OE but not 2-ME. Microglia expressed ERβ and GPR30 but not ERα. 2,3-Bis(4-hydroxyphenyl)-propionitrile (ERβ agonist), but not 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (ERα agonist) or G1 (GPR30 agonist), inhibited microglial proliferation. The antiproliferative effects of estradiol, but not 2-OE or 2-ME, were partially reversed by ICI-182,780 (ERα/β antagonist) but not by 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole (ERα antagonist) or G15 (GPR30 antagonist). Lipopolysaccharide increased microglia iNOS and COX-2 expression and phagocytosing activity of microglia; these effects were inhibited by 2-ME. We conclude that in microglia, 2-ME inhibits proliferation, proinflammatory responses, and phagocytosis. 2-ME partially mediates the effects of estradiol via ER-independent mechanisms involving sequential metabolism of estradiol to 2-OE and 2-ME. 2-ME could be of potential therapeutic use in postischemic stroke injuries. Interindividual differences in estradiol metabolism might affect the

  12. Maternal exposure to estradiol and endocrine disrupting compounds alters the sensitivity of sea urchin embryos and the expression of an orphan steroid receptor.

    PubMed

    Roepke, Troy A; Chang, Ernest S; Cherr, Gary N

    2006-10-01

    Endocrine disrupting compounds (EDCs) are known to affect reproduction and development in marine invertebrates. In previous work, we have shown that developing sea urchin embryos were sensitive to estradiol and estrogenic EDCs at environmentally relevant concentrations in a tamoxifen-sensitive manner (Roepke et al. 2005. Aquat Toxicol 71:155-173). In this study, we report the effects of maternal exposure to EDCs on embryo sensitivity and regulation of an orphan steroid receptor in sea urchin eggs. Maternal exposures were conducted by injecting female Strongylocentrotus purpuratus sea urchins initiating oogenesis with two concentrations of estradiol, octylphenol, tributyltin and o, p-DDD for 8 weeks with an induced spawning before and after the injection cycle. Developing embryos were less sensitive to estradiol following maternal exposure to estradiol, octylphenol and DDD. The steroidogenesis inhibitor, spironolactone, and the aromatase inhibitor, formestane, affected normal sea urchin development with EC50 values of 18 and 2 microM, respectively. Binding of estradiol was demonstrated in homogenates supernatants of sea urchin embryos by filtration centrifugation and column chromatography, but saturation was not reached until 4-6 hr and was highly variable. Analysis of eggs from pre- and post-injection spawns using real-time Q-PCR for the mRNA of an orphan steroid receptor, SpSHR2, shows that receptor mRNA increased in eggs with estradiol, octylphenol and tributyltin but decreased with DDD. RIA showed that estradiol may be present during gastrulation. In summary, maternal exposure to estradiol and EDCs alters embryo sensitivity and regulates the expression of an orphan steroid receptor in the egg.

  13. Lipocalin 2 Deficiency Alters Estradiol Production and Estrogen Receptor Signaling in Female Mice

    PubMed Central

    Guo, Hong; Zhang, Yuanyuan; Brockman, David A.; Hahn, Wendy; Bernlohr, David A.

    2012-01-01

    We have previously characterized lipocalin 2 (Lcn2) as a new adipokine having a critical role in energy and lipid metabolism in male mice. Previous studies by others have suggested that Lcn2 is a putative target gene of estrogens. In this study, we reported the effect of Lcn2 deficiency on estradiol biosynthesis and estrogen receptor signaling in female Lcn2-deficient (Lcn2−/−) mice. We found that Lcn2 expression in white adipose tissue is gender, depot, and age dependent. In female mice, Lcn2 is predominantly expressed in inguinal adipose tissue but at relatively very low levels in perigonadal depot and ovary. After 22 wk of high-fat diet (HFD) feeding or at old age, Lcn2−/− female mice had significantly reduced levels of serum 17β-estradiol and down-regulated expression of estrogen receptor α in multiple metabolic tissues. Consistently, the expression of estrogen-regulated genes involved in cholesterol homeostasis, such as liver X receptor β and low-density lipoprotein receptor was also down-regulated in the adipose tissue of Lcn2−/− mice. These changes were in line with the development of atherogenic dyslipidemia in response to HFD feeding; female Lcn2−/− mice had significantly elevated levels of total cholesterol and low-density lipoprotein cholesterol, whereas reduced high-density lipoprotein cholesterol levels compared with wild-type female mice. Interestingly, when compared with wild-type controls, HFD-fed female Lcn2−/− mice had significantly reduced expression levels of aromatase, a key enzyme regulating estradiol biosynthesis, in adipose tissue. Moreover, Lcn2 deficiency markedly blunted age-related increase in adipose aromatase expression but had no significant impact on age-related reduction in ovarian aromatase expression. Our findings suggest that Lcn2 has a tissue-specific role in adipose estradiol biosynthesis, which may link Lcn2 to obesity- and age-related estradiol production and metabolic complications in females. PMID

  14. Effect of four environmental toxicants on plasma Ca and estradiol 17[beta] and hepatic P450 in laying hens

    SciTech Connect

    Chen, S.W.; Dziuk, P.J.; Francis, B.M. . Dept. of Animal Sciences)

    1994-05-01

    In a previous study, the authors found that administration of phenobarbital to laying hens was associated with an increase in content of liver cytochrome P450 and a reduction of estradiol (E2) in serum. Thus, the authors hypothesized that other xenobiotics such as environmental toxicants that affect P450 might also affect E2 in laying hens. In experiment 1, the authors examined the effect of four environmental pollutants, three of which induced different isoenzymes of P450 and one inhibitor, on circulating E2 and related reproductive functions. Aroclor 1254 (PCB), 20 mg/d; dichlorodiphenyltrichloroethane (DDT), 40 mg/d; or benzo[a]pyrene (BZ), 5 mg/d, was administered for 5 d. An inhibitor, lead acetate, was injected for 2 d. Controls received corn oil or sodium acetate. No significant difference was observed due to administration of lead. Treatment with PCB or DDT decreased the concentration of E2 and increased P450. Only PCB significantly decreased plasma total calcium and egg lay. Therefore in experiment 2, the authors determined the dose-response effect of PCB. The PCB was given orally at doses of 0, 5, 10, and 25 mg in corn oil for 5 d. The depression of concentrations of E2 was associated with the induction of P450 in a dose-dependent manner. Egg production and plasma total calcium were reduced by the two highest doses, but eggshell thickness was not different from control in all regimens. Plasma E2 and plasma total calcium were negatively correlated with induction of P450. BZ is not a strong inducer of P450 and had no effect on E2 or reproduction, whereas DDT and PCB had a profound effect on P450 with consequent depression of circulating E2. These data indicate that the effects of environmental pollutants on reproduction in birds can be mediated through increased P450, thereby increasing the metabolism of steroid hormones and depressing concentration in circulation.

  15. Vasomotor symptoms, estradiol levels and cardiovascular risk profile in women.

    PubMed

    Gast, Gerrie-Cor M; Samsioe, Göran N; Grobbee, Diederick E; Nilsson, Peter M; van der Schouw, Yvonne T

    2010-07-01

    We investigated whether menopausal vasomotor symptoms (VMS) are related to an adverse cardiovascular risk profile. Furthermore, we examined the association between estradiol levels and VMS, and whether an association between VMS and cardiovascular risk factors can be explained by estradiol levels. We used data from a Swedish population-based sample of 5857 women, aged 50-64 years. Data on VMS and potential confounders were collected by questionnaires. Body mass index (BMI), waist hip ratio (WHR), glucose, blood pressure, lipid profile and estradiol levels were measured. Symptoms of flushing/sweats were reported by 55% and sweats by 31% of all women. Estradiol concentrations were significantly lower in women with VMS. After multivariate adjustment, women with symptoms of sweats had a statistically significantly higher BMI, waist hip ratio, total cholesterol level, LDL level, triglycerides level, glucose level, systolic and diastolic blood pressure. These patterns did not change after correction for estradiol. The associations between flushing/sweats combined and cardiovascular risk factors were less pronounced. Women with VMS have a less favorable cardiovascular risk profile. Although estradiol levels were significantly lower among women with VMS, the increased cardiovascular risk profile cannot be explained by circulating estradiol levels. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  16. 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

  17. Liver X receptor agonist treatment significantly affects phenotype and transcriptome of APOE3 and APOE4 Abca1 haplo-deficient mice

    PubMed Central

    Fitz, Nicholas F.; Mounier, Anais; Wolfe, Cody M.; Nam, Kyong Nyon; Reeves, Valerie L.; Kamboh, Hafsa; Koldamova, Radosveta

    2017-01-01

    ATP-binding cassette transporter A1 (ABCA1) controls cholesterol and phospholipid efflux to lipid-poor apolipoprotein E (APOE) and is transcriptionally controlled by Liver X receptors (LXRs) and Retinoic X Receptors (RXRs). In APP transgenic mice, lack of Abca1 increased Aβ deposition and cognitive deficits. Abca1 haplo-deficiency in mice expressing human APOE isoforms, increased level of Aβ oligomers and worsened memory deficits, preferentially in APOE4 mice. In contrast upregulation of Abca1 by LXR/RXR agonists significantly ameliorated pathological phenotype of those mice. The goal of this study was to examine the effect of LXR agonist T0901317 (T0) on the phenotype and brain transcriptome of APP/E3 and APP/E4 Abca1 haplo-deficient (APP/E3/Abca1+/- and APP/E4/Abca1+/-) mice. Our data demonstrate that activated LXRs/RXR ameliorated APOE4-driven pathological phenotype and significantly affected brain transcriptome. We show that in mice expressing either APOE isoform, T0 treatment increased mRNA level of genes known to affect brain APOE lipidation such as Abca1 and Abcg1. In both APP/E3/Abca1+/- and APP/E4/Abca1+/- mice, the application of LXR agonist significantly increased ABCA1 protein level accompanied by an increased APOE lipidation, and was associated with restoration of APOE4 cognitive deficits, reduced levels of Aβ oligomers, but unchanged amyloid load. Finally, using Gene set enrichment analysis we show a significant APOE isoform specific response to LXR agonist treatment: Gene Ontology categories “Microtubule Based Process” and “Synapse Organization” were differentially affected in T0-treated APP/E4/Abca1+/- mice. Altogether, the results are suggesting that treatment of APP/E4/Abca1+/- mice with LXR agonist T0 ameliorates APOE4-induced AD-like pathology and therefore targeting the LXR-ABCA1-APOE regulatory axis could be effective as a potential therapeutic approach in AD patients, carriers of APOEε4. PMID:28241068

  18. Involvement of CART in estradiol-induced anorexia.

    PubMed

    Dandekar, Manoj P; Nakhate, Kartik T; Kokare, Dadasaheb M; Subhedar, Nishikant K

    2012-01-18

    Since estradiol exercises inhibitory effect on food intake, we wanted to find out if this influence of estradiol is mediated by cocaine- and amphetamine-regulated transcript peptide (CART), a well established anorectic agent in the brain. Ovariectomized (OVX) rats, replaced with estradiol to produce estrous-phase like conditions, showed a significant decrease in food intake as compared with that in OVX controls. Intracerebroventricular (icv) administration of CART (0.5-1 μg/rat) to OVX rats, resulted in a dose-dependent reduction in the food intake. The lower dose (0.25 μg) had no effect, and was considered subeffective. In estradiol replaced OVX rats, CART at subeffective dose, further reduced food intake. However, CART failed to reduce food intake in estradiol replaced OVX rats pretreated with anti-estrogenic agent tamoxifen (3 mg/kg, subcutaneous). Administration of CART antibody (1:500 dilution/rat, i.c.v.) significantly attenuated estradiol-induced anorexia in the OVX rats. While estradiol replacement significantly increased CART-immunoreactivity in the cells/fibers of paraventricular nucleus (PVN) of OVX rats, fibers in the anteroventral periventricular nucleus (AVPV), and cells/fibers in the arcuate nucleus (ARC) showed considerable reduction. These changes were attenuated following concurrent injection of tamoxifen to the estradiol replaced OVX rats. However, CART-immunoreactive cells/fibers in the periventricular area did not respond to any of the treatments. We suggest that estradiol treatment might influence the hypothalamic CART system in a site specific manner. While increased CART activity in the PVN might produce anorexia, reduction of CART in ARC and AVPV might represent a compensatory homeostatic response. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. A co culture approach show that polyamine turnover is affected during inflammation in Atlantic salmon immune and liver cells and that arginine and LPS exerts opposite effects on p38MAPK signaling.

    PubMed

    Holen, Elisabeth; Espe, Marit; Andersen, Synne M; Taylor, Richard; Aksnes, Anders; Mengesha, Zebasil; Araujo, Pedro

    2014-04-01

    This study assess which pathways and molecular processes are affected by exposing salmon head kidney cells or liver cells to arginine supplementation above the established requirements for growth support. In addition to the conventional mono cultures of liver and head kidney cells, co cultures of the two cell types were included in the experimental set up. Responses due to elevated levels of arginine were measured during inflammatory (lipopolysaccharide/LPS) and non -inflammatory conditions. LPS up regulated the genes involved in polyamine turnover; ODC (ornithine decarboxylase), SSAT (spermidine/spermine-N1-acetyltransferase) and SAMdc (S-adenosyl methionine decarboxylase) in head kidney cells when co cultured with liver cells. Regardless of treatment, liver cells in co culture up regulated ODC and down regulated SSAT when compared to liver mono cultures. This suggests that polyamines have anti-inflammatory properties and that both salmon liver cells and immune cells seem to be involved in this process. The transcription of C/EBP β/CCAAT, increased during inflammation in all cultures except for liver mono cultures. The observed up regulation of this gene may be linked to glucose transport due to the highly variable glucose concentrations found in the cell media. PPARα transcription was also increased in liver cells when receiving signals from head kidney cells. Gene transcription of Interleukin 1β (IL-1β), Interleukin-8 (IL-8), cyclooxygenase 2 (COX2) and CD83 were elevated during LPS treatment in all the head kidney cell cultures while arginine supplementation reduced IL-1β and IL-8 transcription in liver cells co cultured with head kidney cells. This is probably connected to p38MAPK signaling as arginine seem to affect p38MAPK signaling contrary to the LPS induced p38MAPK signaling, suggesting anti-inflammatory effects of arginine/arginine metabolites. This paper shows that co culturing these two cell types reveals the connection between metabolism and

  20. Estradiol-stimulated growth of MCF-7 tumors implanted in athymic mice: a model to study the tumoristatic action of tamoxifen.

    PubMed

    Gottardis, M M; Robinson, S P; Jordan, V C

    1988-01-01

    Ovariectomized athymic (nude) mice were inoculated (10(7) cells) with the breast cancer cell line, MCF-7, into the axillary mammary fat pads. Tumors did not grow unless animals were implanted with a 1.7 mg estradiol sustained (8-week)-release cholesterol pellet. Co-implantation with tamoxifen (5 mg, 4-week release) caused an inhibition of estradiol-stimulated growth but did not cause tumor growth when implanted alone. The metabolism of [3H]tamoxifen was determined in the athymic mouse bearing MCF-7 tumors. Metabolites in the liver, uterus and tumor were determined by TLC. The principal metabolite in each of the tissues was 4-hydroxytamoxifen (by comparison of Rfs with authentic standards). Studies with 4-hydroxytamoxifen and N-desmethyltamoxifen (the principal metabolites in patients) showed that each was effective in inhibiting estradiol-stimulated tumor growth. However, tumor growth could be reactivated by treatment with estradiol alone. In a separate experiment, tumor-implanted animals were treated with tamoxifen for 1, 2 and 6 months. Tamoxifen did not cause tumor growth. Nevertheless, tumor growth was reactivated by estradiol on each occasion. These studies confirm the tumoristatic actions of tamoxifen and strongly support the view that therapy must be given indefinitely to patients to control tumor recurrence. The athymic mouse model can be used in the future to determine the efficacy of novel antiestrogens and the development of antiestrogen drug resistance.

  1. Liver choline dehydrogenase and kidney betaine-homocysteine methyltransferase expression are not affected by methionine or choline intake in growing rats.

    PubMed

    Slow, Sandy; Garrow, Timothy A

    2006-09-01

    Choline dehydrogenase (CHDH) and betaine-homocysteine methyltransferase (BHMT) are 2 enzymes involved in choline oxidation. BHMT is expressed at high levels in rat liver and its expression is regulated by dietary Met and choline. BHMT is also found in rat kidney, albeit in substantially lower amounts, but it is not known whether kidney BHMT expression is regulated by dietary Met or choline. Similarly, CHDH activity is highest in the liver and kidney, but the regulation of its expression by diet has not been thoroughly investigated. Sprague Dawley rats ( approximately 50 g) were fed, for 9 d in 2 x 3 factorial design (n = 8), an l-amino acid-defined diet varying in l-Met (0.125, 0.3, or 0.8%) and choline (0 or 25 mmol/kg diet). Liver and kidney BHMT and CHDH were assessed using enzymatic, Western blot, and real-time PCR analyses. Liver samples were also fixed for histological analysis. Liver BHMT activity was 1.3-fold higher in rats fed the Met deficient diet containing choline, which was reflected in corresponding increases in mRNA content and immunodetectable protein. Independent of dietary choline, supplemental Met increased hepatic BHMT activity approximately 30%. Kidney BHMT and liver CHDH expression were refractory to these diets. Some degree of fatty liver developed in all rats fed a choline-devoid diet, indicating that supplemental Met cannot completely compensate for the lack of dietary choline in growing rats.

  2. Long-term feeding a plant-based diet devoid of marine ingredients strongly affects certain key metabolic enzymes in the rainbow trout liver.

    PubMed

    Véron, Vincent; Panserat, Stéphane; Le Boucher, Richard; Labbé, Laurent; Quillet, Edwige; Dupont-Nivet, Mathilde; Médale, Françoise

    2016-04-01

    Incorporation of a plant blend in the diet can affect growth parameters and metabolism in carnivorous fish. We studied for the first time the long-term (1 year) metabolic response of rainbow trout fed from first feeding with a plant-based diet totally devoid of marine ingredients. Hepatic enzymes were analyzed at enzymatic and molecular levels, at 3, 8 and 24 h after the last meal to study both the short-term effects of the last meal and long-term effects of the diet. The results were compared with those of fish fed a control diet of fish meal and fish oil. Growth, feed intake, feed efficiency and protein retention were lower in the group fed the plant-based diet. Glucokinase and pyruvate kinase activity were lower in the livers of trout fed the plant-based diet which the proportion of starch was lower than in the control diet. Glutamate dehydrogenase was induced by the plant-based diet, suggesting an imbalance of amino acids and a possible link with the lower protein retention observed. Gene expression of delta 6 desaturase was higher in fish fed the plant-based diet, probably linked to a high dietary level of linolenic acid and the absence of long-chain polyunsaturated fatty acids in vegetable oils. Hydroxymethylglutaryl-CoA synthase expression was also induced by plant-based diet because of the low rate of cholesterol in the diet. Changes in regulation mechanisms already identified through short-term nutritional experiments (<12 weeks) suggest that metabolic responses are implemented at short term and remain in the long term.

  3. Primary induction of vitellogenin mRNA in the rooster by 17beta-estradiol.

    PubMed Central

    Burns, A T; Deeley, R G; Gordon, J I; Udell, D S; Mullinix, K P; Goldberger, R F

    1978-01-01

    We have studied the kinetics of vitellogenin mRNA accumulation in rooster liver after a primary injection of 17beta-estradiol. The levels of vitellogenin mRNA have been determined both by hybridization of total cellular RNA to vitellogenin cDNA and by translation of vitellogenin mRNA in a wheat germ cell-free system. The results obtained by both methods of analysis are in good agreement and indicate that vitellogenin mRNA is present in the liver of normal roosters at a level of 0-5 molecules per liver cell and increases in amount during the 3 days following injection of estrogen, reaching a level of almost 6000 molecules per cell at the peak of the response. The level of vitellogenin mRNA declined exponentially during the next 14 days with a half-life of 29 hr, reaching a level of less than 10 molecules per cell at 17 days after injection of the hormone. The levels of vitellogenin mRNA after stimulation with estrogen have been correlated with the in vivo rate of synthesis of the vitellogenin polypeptide. The results indicate that the rate of vitellogenin synthesis is closely correlated with the level of vitellogenin mRNA. On the basis of these findings, we conclude that vitellogenin mRNA does not exist in the liver in an untranslated form after withdrawal from estrogen. PMID:273910

  4. The endogenous estradiol metabolite 2-methoxyestradiol reduces atherosclerotic lesion formation in female apolipoprotein E-deficient mice.

    PubMed

    Bourghardt, Johan; Bergström, Göran; Krettek, Alexandra; Sjöberg, Sara; Borén, Jan; Tivesten, Asa

    2007-09-01

    Estradiol, the major endogenous estrogen, reduces experimental atherosclerosis and metabolizes to 2-methoxyestradiol in vascular cells. Currently undergoing evaluation in clinical cancer trials, 2-methoxyestradiol potently inhibits cell proliferation independently of the classical estrogen receptors. This study examined whether 2-methoxyestradiol affects atherosclerosis development in female mice. Apolipoprotein E-deficient mice, a well-established mouse model of atherosclerosis, were ovariectomized and treated through slow-release pellets with placebo, 17beta-estradiol (6 microg/d), or 2-methoxyestradiol [6.66 microg/d (low-dose) or 66.6 microg/d (high-dose)]. After 90 d, body weight gain decreased and uterine weight increased in the high-dose but not low-dose 2-methoxyestradiol group. En face analysis showed that the fractional area of the aorta covered by atherosclerotic lesions decreased in the high-dose 2-methoxyestradiol (52%) but not in the low-dose 2-methoxyestradiol group. Total serum cholesterol levels decreased in the high- and low-dose 2-methoxyestradiol groups (19%, P < 0.05 and 21%, P = 0.062, respectively). Estradiol treatment reduced the fractional atherosclerotic lesion area (85%) and decreased cholesterol levels (42%). In conclusion, our study shows for the first time that 2-methoxyestradiol reduces atherosclerotic lesion formation in vivo. The antiatherogenic activity of an estradiol metabolite lacking estrogen receptor activating capacity may argue that trials on cardiovascular effects of hormone replacement therapy should use estradiol rather than other estrogens. Future research should define the role of 2-methoxyestradiol as a mediator of the antiatherosclerotic actions of estradiol. Furthermore, evaluation of the effects of 2-methoxyestradiol on cardiovascular disease endpoints in ongoing clinical trials is of great interest.

  5. Identification of centrarchid hepcidins and evidence that 17β-estradiol disrupts constitutive expression of hepcidin-1 and inducible expression of hepcidin-2 in largemouth bass (Micropterus salmoides)

    USGS Publications Warehouse

    Robertson, L.S.; Iwanowicz, L.R.; Marranca, J.M.

    2009-01-01

    Hepcidin is a highly conserved antimicrobial peptide and iron-regulatory hormone. Here, we identify two hepcidin genes (hep-1 and hep-2) in largemouth bass (Micropterus salmoides) and smallmouth bass (Micropterus dolomieu). Hepcidin-1 contains a putative ATCUN metal-binding site in the amino-terminus that is missing in hepcidin-2, suggesting that hepcidin-1 may function as an iron-regulatory hormone. Both hepcidins are predominately expressed in the liver of largemouth bass, similar to other fish and mammals. Experimental exposure of pond-raised largemouth bass to 17β-estradiol and/or the bacteria Edwardsiella ictaluri led to distinct changes in expression of hep-1 and hep-2. Estradiol reduced the constitutive expression of hep-1 in the liver. Bacterial exposure induced expression of hep-2, suggesting that hepcidin-2 may have an antimicrobial function, and this induction was abolished by estradiol. To our knowledge, this is the first report of the regulation of hepcidin expression by estradiol in either fish or mammals.

  6. Identification of centrarchid hepcidins and evidence that 17beta-estradiol disrupts constitutive expression of hepcidin-1 and inducible expression of hepcidin-2 in largemouth bass (Micropterus salmoides).

    PubMed

    Robertson, Laura S; Iwanowicz, Luke R; Marranca, Jamie Marie

    2009-06-01

    Hepcidin is a highly conserved antimicrobial peptide and iron-regulatory hormone. Here, we identify two hepcidin genes (hep-1 and hep-2) in largemouth bass (Micropterus salmoides) and smallmouth bass (Micropterus dolomieu). Hepcidin-1 contains a putative ATCUN metal-binding site in the amino-terminus that is missing in hepcidin-2, suggesting that hepcidin-1 may function as an iron-regulatory hormone. Both hepcidins are predominately expressed in the liver of largemouth bass, similar to other fish and mammals. Experimental exposure of pond-raised largemouth bass to 17beta-estradiol and/or the bacteria Edwardsiella ictaluri led to distinct changes in expression of hep-1 and hep-2. Estradiol reduced the constitutive expression of hep-1 in the liver. Bacterial exposure induced expression of hep-2, suggesting that hepcidin-2 may have an antimicrobial function, and this induction was abolished by estradiol. To our knowledge, this is the first report of the regulation of hepcidin expression by estradiol in either fish or mammals.

  7. Endotoxin disrupts the estradiol-induced luteinizing hormone surge: interference with estradiol signal reading, not surge release.

    PubMed

    Battaglia, D F; Beaver, A B; Harris, T G; Tanhehco, E; Viguié, C; Karsch, F J

    1999-06-01

    Three experiments were conducted to investigate whether the immune/inflammatory stimulus endotoxin disrupts the estradiol-induced LH surge of the ewe. Ovariectomized sheep were set up in an artificial follicular phase model in which luteolysis is simulated by progesterone withdrawal and the follicular phase estradiol rise is reproduced experimentally. In the first experiment, we tested the hypothesis that endotoxin interferes with the estradiol-induced LH surge. Ewes were either infused with endotoxin (300 ng/kg/h, i.v.) for 30 h beginning at onset of a 48-h estradiol stimulus or sham infused as a control. Endotoxin significantly delayed the time to the LH surge (P < 0.01), but did not alter surge amplitude, duration, or incidence. The second experiment tested the hypothesis that the delaying effects of endotoxin on the LH surge depend on when endotoxin is introduced relative to the onset of the estradiol signal. Previous work in the ewe has shown that a 14-h estradiol signal is adequate to generate GnRH and LH surges, which begin 6-8 h later. Thus, we again infused endotoxin for 30 h, but began it 14 h after the onset of the estradiol signal. In contrast to the first experiment, endotoxin given later had no effect on any parameter of the LH surge. In the third experiment, we tested the hypothesis that endotoxin acts during the first 14 h to disrupt the initial activating effects of estradiol. Estradiol was delivered for just 14 h, and endotoxin was infused only during this time. Under these conditions, endotoxin blocked the LH surge in five of eight ewes. In a similar follow-up study, endotoxin again blocked the LH surge in six of seven ewes. We conclude that endotoxin can disrupt the estradiol-induced LH surge by interfering with the early activating effects of the estradiol signal during the first 14 h (reading of the signal). In contrast, endotoxin does not disrupt later stages of signal processing (i.e. events during the interval between estradiol signal

  8. Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by estradiol

    PubMed Central

    Caballero, Ignacio; Boyd, James; Almiñana, Carmen; Sánchez-López, Javier A.; Basatvat, Shaghayegh; Montazeri, Mehrnaz; Maslehat Lay, Nasim; Elliott, Sarah; Spiller, David G.; White, Michael R. H.; Fazeli, Alireza

    2017-01-01

    Toll-like receptors (TLRs) are major players of the innate immune system. Once activated, they trigger a signalling cascade that leads to NF-κB translocation from the cytoplasm to the nucleus. Single cell analysis shows that NF-κB signalling dynamics are a critical determinant of transcriptional regulation. Moreover, the outcome of innate immune response is also affected by the cross-talk between TLRs and estrogen signalling. Here, we characterized the dynamics of TLR5 signalling, responsible for the recognition of flagellated bacteria, and those changes induced by estradiol in its signalling at the single cell level. TLR5 activation in MCF7 cells induced a single and sustained NF-κB translocation into the nucleus that resulted in high NF-κB transcription activity. The overall magnitude of NF-κB transcription activity was not influenced by the duration of the stimulus. No significant changes are observed in the dynamics of NF-κB translocation to the nucleus when MCF7 cells are incubated with estradiol. However, estradiol significantly decreased NF-κB transcriptional activity while increasing TLR5-mediated AP-1 transcription. The effect of estradiol on transcriptional activity was dependent on the estrogen receptor activated. This fine tuning seems to occur mainly in the nucleus at the transcription level rather than affecting the translocation of the NF-κB transcription factor. PMID:28112187

  9. Evidence for regulatory genes on mouse chromosome 7 that affect the quantitative expression of proteins in the fetal and newborn liver.

    PubMed Central

    Giometti, C S; Gemmell, M A; Taylor, J; Tollaksen, S L; Angeletti, R; Gluecksohn-Waelsch, S

    1992-01-01

    A series of deletions around the albino locus on mouse chromosome 7 is believed to include one or more regulatory genes that control the activities of a cluster of liver enzymes. To further characterize the functions of this region of the mouse genome, we have used quantitative two-dimensional electrophoresis to analyze the effects of two of these deletions, c3H and c14CoS, on the expression of liver proteins. More than 400 distinct protein gene products were quantitated in livers from fetal and newborn wild-type homozygous (cch/cch), heterozygous (cch/c3H or cch/c14CoS), and deletion homozygous (c3H/c3H or c14CoS/c14CoS) mice. Livers of fetal and newborn c3H heterozygotes and homozygous wild-type littermates produced qualitatively identical protein patterns after two-dimensional electrophoresis. In livers of c3H homozygous fetuses, however, abnormal amounts (either increased or decreased relative to homozygous wild-type and heterozygous littermates) of 29 proteins were found. Twenty-eight of these 29 protein anomalies were also found in livers of newborn c3H homozygotes. Livers of fetal and newborn mice homozygous for the c14CoS deletion, which overlaps the c3H deletion and produces a similar phenotype, expressed normal amounts of these proteins. One of the 29 proteins (MSN807) has an amino-terminal sequence similar to a 23-kDa translationally controlled protein abundant in mouse erythroleukemia and sarcoma-180 cells. These results suggest that normal chromosome 7 contains genes, located within the region of the c3H but not the c14CoS deletion, that regulate the abundance of specific proteins in the liver. These proteins cannot be related to the phenotypic alterations shared by the c3H and c14CoS deletions. Images PMID:1549608

  10. [Extracorporeal liver support of liver failure].

    PubMed

    Gerth, Hans Ulrich; Pohlen, Michele; Pavenstädt, Hermann; Schmidt, Hartmut

    2017-03-14

    Extracorporeal liver support can be classified into cell-free, artificial methods (artificial liver support, ALS) and cell-based bioartificial methods (bioartificial liver support, BLS). ALS improves biochemical parameters of liver failure by the simultaneous removal of protein-bound and water-soluble substances. Here, the MARS therapy belongs to the most studied methods with a proved beneficial effect on hepatic encephalopathy (HE), hepatorenal syndrome (HRS) or hyperbilirubinemia. However, a general survival advantage of any liver support for liver failure has not been shown yet and is restricted to meta-analyses or patient subgroups. There are no prospective randomized studies on the treatment of liver failure by intoxication. However, several case series report positive treatment effects using the MARS system, particularly in mushroom poisoning or acetaminophen intoxication. In acute liver failure (ALF) studies, the usage of BLS showed no survival advantage. Using ALS systems, a positive effect on mortality could be demonstrated in patient subgroups after several consecutive MARS therapies. The first randomized controlled trial demonstrating a survival benefit used large-volume plasmapheresis. Apparently, immunomodulatory and hemodynamic effects of the treatment play a crucial role in this context. In patients with acute-on-chronic liver failure (ACLF) accompanied by hyperbilirubinemia without any further organ failure (singular hepatic dysfunction), prognostic favorable effects by using a BLS system have been shown. However, once other extrahepatic organ systems are affected, indicating a progressive transition to multi-organ failure, a survival advantage could be achieved with the MARS and Prometheus system. Decisive for a successful therapy is the exact indication of the respective liver dialysis procedure for this very heterogeneous disease. Future studies are needed to define more accurate patient selection criteria for each liver support.

  11. Activity of phospholipase C and release of prostaglandin F2 alpha by endometrial tissue from ovariectomized ewes receiving progesterone and estradiol.

    PubMed

    Raw, R E; Silvia, W J

    1991-03-01

    Progesterone and estradiol interact to regulate secretion of prostaglandin (PG) F2 alpha from the ovine endometrium in response to oxytocin. Two experiments were conducted to determine if these effects were due to changes in activity of phospholipase C or in the second messenger responsive pathways that regulate production of PGF2 alpha. In both experiments, ovariectomized ewes were assigned to one of four treatment groups (control, estradiol, progesterone, progesterone and estradiol). Steroids were administered, in vivo, to mimic the changes that occur during the estrous cycle. On Day 16 of steroid treatment, endometrial tissue was collected and incubated, in vitro, to measure activity of phospholipase C and release of PGF2 alpha. Treatment with progesterone, in vivo, enhanced basal and oxytocin-induced activity of phospholipase C and release of PGF2 alpha, in vitro. Estradiol suppressed oxytocin-induced activity of phospholipase C, both in the presence and absence of progesterone. In contrast to its effects on phospholipase C, estradiol inhibited basal and oxytocin-induced release of PGF2 alpha when administered alone, but not when administered with progesterone. Steroids had similar effects on the release of PGF2 alpha induced by phorbol 12-myristate 13-acetate and A23187. It was concluded that progesterone and estradiol regulate endometrial release of PGF2 alpha by affecting both the activity of phospholipase C and its associated second messenger responsive pathways that may regulate production of PGF2 alpha.

  12. Physiological and brain alterations produced by high-fat diet in male and female rats can be modulated by increased levels of estradiol during critical periods of development.

    PubMed

    Carrillo, Beatriz; Collado, Paloma; Díaz, Francisca; Chowen, Julie A; Pérez-Izquierdo, Mª Ángeles; Pinos, Helena

    2017-07-11

    Overnutrition due to a high-fat diet (HFD) can increase the vulnerability of the metabolic system to maladjustments. Estradiol has an inhibitory role on food intake and this hormone has demonstrated to be a crucial organizer during brain development. Our aim was to determine whether increased levels of estradiol in the early postnatal period modulate the alterations in metabolism and brain metabolic circuits produced by overnutrition. Twenty-four male and 24 female Wistar rats were submitted to a HFD (34.9% fat) or a control diet (5% fat) from gestational day 6. From postnatal (P) 6 to P13, both control and HFD groups were administered a s.c. injection of vehicle or estradiol benzoate (0.4 mg/kg), resulting in eight experimental groups (n = 6 in each group). Body weight, food intake and subcutaneous, visceral, and brown fat pads were measured. Agouti-related peptide, neuropeptide Y, orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay and plasma estradiol levels were measured by ELISA. Males fed a HFD showed an increase in body weight and the amount of visceral and subcutaneous fat, which was coincident with an increase in the number of kilocalories ingested. Neonatal estradiol treatment restored the body weight and subcutaneous fat of HFD males to control levels. Hypothalamic POMC mRNA levels in HFD females were increased with respect to control females. This increase was reverted with estradiol treatment during development. HFD and estradiol treatment have different effects on males and females. Overnutrition affects physiological parameters, such as body weight, visceral, and subcutaneous fat content, in males, while females present alterations in hypothalamic POMC mRNA levels. Hence, the increase in estradiol levels during a period that is critical for the programing of the feeding system can modulate some of the alterations produced by the continuous intake of high-fat content food.

  13. Liver biopsy

    MedlinePlus

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  14. [Photodegradation of 17beta-estradiol induced by Chlorella vulgaris].

    PubMed

    Ge, Liyun; Deng, Huanhuan; Wu, Feng; Weng, Yue; Deng, Nansheng

    2004-07-01

    The study showed that when exposed to high-pressure Hg-lamp (HPML, lambda(max) > or = 365 nm), and the concentration of Chlorella vulgaris was 4.0 x 10(10) cells x L(-1), the photodegradation rate of 17beta-estradiol could reach to 37%. When the concentration of Chlorella vulgaris was 4.2 x 10(10) cells x L(-1), the photodegradation of 1.5 x 10(-5) - 6.0 x 10(-5) mol x L(-1) 17beta-estradiol in aqueous solutions was pseudo-first order reaction. Increasing the initial concentration of 17beta-estradiol could lower its photodegradation rate. The influence of light intension and Chlorella vulgaris concentration on the photodegradation of 17beta-estradiol was also studied in this paper.

  15. 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.

  16. Neuroprotective effects of estradiol-17beta: implications for psychiatric disorders.

    PubMed

    Kölsch, H; Rao, M L

    2002-11-01

    Estradiol-17beta is the most potent female sex hormone. In addition to its role in the control of primary and secondary sexual characteristics, it also influences the development of the brain. Furthermore, estradiol-17beta possesses neuroprotective properties that are mediated via receptor action and also independently of receptors. Several processes that are regulated by estradiol-17beta might influence the expression of Alzheimer's disease and schizophrenia. Differences between the sexes have been described in both disorders, and it has been suggested that these may be due to the action of oestrogens. Long-term oestrogen replacement has proved to be beneficial in the prevention and treatment of Alzheimer's disease and schizophrenia. The results, however, are controversial. Preliminary in vitro and in vivo findings, which are summarised in this review, encourage further studies with estradiol-17beta or its analogues as potential adjunctive interventions particularly in "negative syndrome" schizophrenia and in Alzheimer's disease.

  17. Estradiol and cognitive function: Past, present and future

    PubMed Central

    Luine, Victoria N.

    2014-01-01

    A historical perspective on estradiol’s enhancement of cognitive function is presented, and research, primarily in animals, but also in humans, is reviewed. Data regarding the mechanisms underlying the enhancements are discussed. Newer studies showing rapid effects of estradiol on consolidation of memory through membrane interactions and activation of inter-cellular signaling pathways are reviewed as well as studies focused on traditional genomic mechanisms. Recent demonstrations of intra-neuronal estradiol synthesis and possible actions as a neurosteroid to promote memory are discussed. This information is applied to the critical issue of the current lack of effective hormonal (or other) treatments for cognitive decline associated with menopause and aging. Finally, the critical period hypothesis for estradiol effects is discussed along with novel strategies for hormone/drug development. Overall, the historical record documents that estradiol positively impacts some aspects of cognitive function, but effective therapeutic interventions using this hormone have yet to be realized. PMID:25205317

  18. Mitochondrial membrane potential changes in osteoblasts treated with parathyroid hormone and estradiol.

    PubMed

    Troyan, M B; Gilman, V R; Gay, C V

    1997-06-15

    This study assessed mitochondrial membrane potential changes in cultured osteoblasts treated with hormones known to regulate osteoblasts. A fluorescent carbocyanine dye, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine++ + iodide, also called JC-1, was used as a probe. JC-1 emits photons at 585 nm (orange-red) when the membrane potential in mitochondria is highly negative, but when the potential becomes reduced emission occurs at 527 nm (green). Osteoblasts were rinsed in serum-free medium for 5 min, then loaded with 1 x 10(-6) M JC-1 for 10 min. The distribution and intensity of JC-1 fluorescence were evaluated with a laser-scanning confocal microscope system. Hormone treatments included parathyroid hormone (PTH; 10(-8) M), 17beta-estradiol (10(-8) M), and thyroxine (T4; 10(-8) M). The potassium ionophore valinomycin (10(-6) M) was used as a control since it is known to disrupt the electrochemical gradient of mitochondria without interfering with the pH gradient. Valinomycin caused a profound, rapid increase (22.5% above untreated values) in the green/red ratio, which indicated a lowering of the mitochondrial membrane potential in all samples evaluated. PTH caused a less pronounced, but significant (7-14%), reduction in membrane potential in all cells examined. PTH is known to affect osteoblasts in a number of ways and is inhibitory to mitochondrial respiration; the results confirm this effect. For estradiol, half of the cells responded at a significant level, with a membrane potential reduction of 6 to 13% being recorded; the other half did not respond. Thyroxine did not alter mitochondrial membrane potential. Responses were detectable within 20 s for valinomycin, but occurred at a slower rate, over 200 to 300 s, following PTH and estradiol treatment. Responses to PTH and estradiol could be due to mitochondrial uptake of cytosolic Ca2+.

  19. [Hormone replacement therapy with transdermal estradiol lowers insulin-cortisol and lipoproteins levels in postmenopausal women].

    PubMed

    Basurto, Lourdes; Saucedo, Renata; Ochoa, Raquel; Hernández, Marcelino; Zárate, Arturo

    2002-10-01

    Increased levels of circulating insulin and cortisol, interpreted as part of aging process, have been associated with an increase risk of developing cardiovascular disease and diabetes mellitus. Because estrogens affect insulin balance, hypoestrogenism in menopausal women may lead to elevations in both insulin and cortisol. The purpose of the present study was to determine the effect of transdermal estradiol administration on the insulin-cortisol binomial. A prospective study was carried out in 30 menopausal women aged 48 to 55 yr, receiving transdermal estradiol 50 micrograms/day during three months. Ten healthy menopausal women (49 to 58 yr) were the control group. Serum levels of cortisol, insulin, lipoproteins, and leptin were quantified by specific assays before and after 3 months of transdermal estradiol therapy. Baseline cortisol levels decreased significantly from 143.4 +/- 10.6 ng/mL to 110.2 +/- 6.7 ng/mL (M +/- SE) (p < 0.001) after 3 months of transdermal estradiol. In parallel, augmented baseline insulin levels diminished significantly from 26.1 +/- 2.0 microlitersU/mL to 21.7 +/- 1.2; (M +/- SE) (p < 0.05). Glucose level were unaffected by this therapy, but it was restored to normal the augmented baseline levels of both triglycerides and low-density cholesterol. Total cholesterol and high-density-cholesterol as well as circulating leptin were unchanged. Transdermal estrogen induced-decrease in circulating cortisol, insulin, triglycerides, and low-density cholesterol to normal values may have a beneficial metabolic effect in menopausal women.

  20. Neonatal exposure to estradiol valerate increases dopamine content in nigrostriatal pathway during adulthood in the rat.

    PubMed

    Cruz, G; Riquelme, R; Espinosa, P; Jara, P; Dagnino-Subiabre, A; Renard, G M; Sotomayor-Zárate, R

    2014-05-01

    Research in programming has focused in the study of stimuli that affect sensitive periods of development such as prenatal and neonatal stage. We previously showed that exposure to estradiol valerate to female rats during the first 12 h of life increased catecholamine content in ventromedial-arcuatus hypothalamus of the adult rat. However, changes in others dopaminergic circuits have not been studied. The purpose of this work was to determine the neurotransmitters changes induced by neonatal estradiol valerate (0.1 mg/50 μl s. c. per rat) administration on nigrostriatal pathway of adult female rats. Sesame oil (50 μl s. c. per rat) was administered in a control parallel group. EV-1 adult rats presented effective markers of long-term estrogenization as decreased serum levels of progesterone and a reduction in the size of estrogen-sensitive organs. In the brain, neonatal estradiol valerate administration led to a significant increase in dopamine content in striatum, substantia nigra and ventral tegmental area. With respect to the contents of dopamine metabolites, only 3-methoxytyramine content increased in substantia nigra and ventral tegmental area. In addition, the content of noradrenaline increased only in striatum. Interestingly, estrogenized rats lacked locomotor activity induced by acute dose of amphetamine (1 mg/kg i. p.). Altogether, these results show that neonatal exposure to estradiol valerate permanently modified the content of monoamine neurotransmitters in nigrostriatal pathway and amphetamine-induced locomotor activity of adult female rats. This might imply that estrogenized rats could have changes in the expression of key proteins in dopaminergic regulation, as tyrosine hydroxylase and dopamine transporter. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Free estradiol and sex hormone-binding globulin.

    PubMed

    Rosner, William

    2015-07-01

    SHBG is a plasma protein that participates in the regulation of free estradiol and free testosterone in plasma. We discuss the concept of the nature of a free estradiol and how best to ascertain its value. It can be measured or calculated; the ways in which this can be done are explored along with the advantages and disadvantages of each. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. 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.

  3. Transdermal 17-beta estradiol replacement therapy reduces megakaryocyte GPVI expression.

    PubMed

    Geng, Hongquan; Zhang, Hui; Zhang, Wei; Nieswandt, Bernhard; Bray, Paul F; Leng, Xinghong

    2008-01-01

    The platelet-collagen interaction is a critical early event in arterial thrombus formation, and platelet GPVI is the major activating receptor for collagen. We have previously used a mouse model to demonstrate that the estrogen effects on platelets depend upon the agonist, estrogen formulation and route of administration. In the current study we used a model of transdermal estradiol (E2) administration to ovariectomized mice to address the potential inhibitory effects of E2 on platelet GPVI. Platelet GPVI expression was reduced after transdermal E2 replacement therapy (p affect centrally on megakaryocyte GPVI to regulate platelet GPVI and function.

  4. 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

    USDA-ARS?s Scientific Manuscript database

    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) ...

  5. ESTRADIOL RAPIDLY MODULATES ODOR RESPONSES IN MOUSE VOMERONASAL SENSORY NEURONS

    PubMed Central

    CHERIAN, S.; LAM, Y. WAI; MCDANIELS, I.; STRUZIAK, M.; DELAY, R. J.

    2014-01-01

    In rodents, many social behaviors are driven by the sense of smell. The vomeronasal organ (VNO), part of the accessory olfactory system mediates many of these chemically driven behaviors. The VNO is heavily vascularized, and is readily accessible to circulating peptide or steroid hormones. Potentially, this allows circulating hormones to alter behavior through modulating the output of the primary sensory neurons in the VNO, the vomeronasal sensory neurons (VSNs). Based on this, we hypothesized that steroid hormones, in particular 17β-estradiol, would modulate activity of VSNs. In this paper, we show that the estrogen receptors, GPR30 and ERα, were present in VSNs and that estradiol may be synthesized locally in the VNO. Our results also showed that 17β-estradiol decreased responses of isolated VSNs to dilute urine, a potent natural stimulus, with respect to current amplitudes and depolarization. Further, 17β-estradiol increased the latency of the first action potential (AP) and the AP amplitude. Additionally, calcium responses to sulfated steroids (present in the low molecular weight fraction of urine) that act as ligands for apical vomeronasal receptors were decreased by 17β-estradiol. In conclusion, we show that estradiol modulates odorant responses mediated by VSNs and hence paves the way for future studies to better understand the mechanisms by which odorant mediated behavior is altered by endocrine status of the animal. PMID:24680884

  6. Estradiol Increases Mucus Synthesis in Bronchial Epithelial Cells

    PubMed Central

    Tam, Anthony; Wadsworth, Samuel; Dorscheid, Delbert; Man, Shu-Fan Paul; Sin, Don D.

    2014-01-01

    Airway epithelial mucus hypersecretion and mucus plugging are prominent pathologic features of chronic inflammatory conditions of the airway (e.g. asthma and cystic fibrosis) and in most of these conditions, women have worse prognosis compared with male patients. We thus investigated the effects of estradiol on mucus expression in primary normal human bronchial epithelial cells from female donors grown at an air liquid interface (ALI). Treatment with estradiol in physiological ranges for 2 weeks caused a concentration-dependent increase in the number of PAS-positive cells (confirmed to be goblet cells by MUC5AC immunostaining) in ALI cultures, and this action was attenuated by estrogen receptor beta (ER-β) antagonist. Protein microarray data showed that nuclear factor of activated T-cell (NFAT) in the nuclear fraction of NHBE cells was increased with estradiol treatment. Estradiol increased NFATc1 mRNA and protein in ALI cultures. In a human airway epithelial (1HAE0) cell line, NFATc1 was required for the regulation of MUC5AC mRNA and protein. Estradiol also induced post-translational modification of mucins by increasing total fucose residues and fucosyltransferase (FUT-4, -5, -6) mRNA expression. Together, these data indicate a novel mechanism by which estradiol increases mucus synthesis in the human bronchial epithelium. PMID:24964096

  7. Social regulation of plasma estradiol concentration in a female anuran.

    PubMed

    Lynch, Kathleen S; Wilczynski, Walter

    2006-06-01

    The behavior of an individual within a social aggregation profoundly influences behavior and physiology of other animals within the aggregation in such a way that these social interactions can enhance reproductive success, survival and fitness. This phenomenon is particularly important during the breeding season when males and female must synchronize their reproductive efforts. We examined whether exposure to conspecific social cues can elevate sex steroid levels, specifically estradiol and androgens, in female túngara frogs (Physalaemus pustulosus). We compared plasma estradiol and androgen concentrations in wild-caught females before and after exposure to either natural mate choruses or random tones. After exposure to mate choruses for 10 consecutive nights, estradiol concentrations were significantly elevated whereas there was no significant elevation in estradiol concentrations in the group of females exposed to random tones for 10 nights. Plasma androgen concentrations were not significantly changed after exposure to either natural mate choruses or random tones for 10 consecutive nights. Social modulation of estradiol concentrations may be important in maintaining a female's reproductive state while males are chorusing. To our knowledge, this is the first study to demonstrate social regulation of estradiol concentration in female anurans.

  8. Gut microbiota and liver diseases

    PubMed Central

    Minemura, Masami; Shimizu, Yukihiro

    2015-01-01

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

  9. Temporal changes in gene expression in rainbow trout exposed to ethynyl estradiol.

    PubMed

    Hook, Sharon E; Skillman, Ann D; Small, Jack A; Schultz, Irvin R

    2007-02-01

    We examined changes in the genomic response during continuous exposure to the xenoestrogen ethynyl estradiol. Isogenic rainbow trout Oncorhynchus mykiss were exposed to nominal concentrations of 100 ng/L ethynyl estradiol (EE2) for a period of 3 weeks. At fixed time points within the exposure, fish were euthanized, livers harvested and RNA extracted. Fluorescently labeled cDNA were generated and hybridized against a commercially available Salmonid array (GRASP project, University of Victoria, Canada) spotted with 16,000 cDNAs. The slides were scanned to measure abundance of a given transcript in each sample relative to controls. Data were analyzed via Genespring (Silicon Genetics) to identify a list of up and down regulated genes, and to determine gene clustering patterns that can be used as "expression signatures". Gene ontology was determined using the annotation available from the GRASP website. Our analysis indicates each exposure time period generated specific gene expression profiles. Changes in gene expression were best understood by grouping genes by their gene expression profiles rather than examining fold change at a particular time point. Many of the genes commonly used as biomarkers of exposure to xenoestrogens were not induced initially and did not have gene expression profiles typical of the majority of genes with altered expression.

  10. Dataset of liver proteins of eu- and hypothyroid rats affected in abundance by any of three factors: in vivo exposure to hexabromocyclododecane (HBCD), thyroid status, gender differences.

    PubMed

    Miller, I; Renaut, J; Cambier, S; Murk, A J; Gutleb, A C; Serchi, T

    2016-09-01

    Male Wistar rats with different thyroid status (eu-, hypothyroid) were exposed to 0, 3 or 30 mg/kg body weight of the flame retardant HBCD for 7 days and obtained data compared with a previous study in females, "Hexabromocyclododecane (HBCD) induced changes in the liver proteome of eu- and hypothyroid female rats" (Miller et al., 2016) [1]. Specifically, proteomic investigation of liver protein patterns obtained by 2D-DIGE was performed and differences between animals groups recorded, based on the factors exposure, thyroid status and gender. All proteins with significantly changed abundance in any of these comparisons were identified by mass spectrometry. General, hormone and proteomic data of both the present and the previous studies are discussed in Miller et al. (2016) [1] and in "Gender specific differences in the liver proteome of rats exposed to hexabromocyclododecane (HBCD)" Miller et al. (2016) [2].

  11. Nutrigenomic profiling of transcriptional processes affected in liver and distal intestine in response to a soybean meal-induced nutritional stress in Atlantic salmon (Salmo salar).

    PubMed

    De Santis, Christian; Bartie, Kerry L; Olsen, Rolf E; Taggart, John B; Tocher, Douglas R

    2015-09-01

    The aim of the present study was to generate an experimental model to characterize the nutrigenomic profile of a plant-derived nutritional stress. Atlantic salmon (Salmo salar) was used as the model species. The nutritional stress was induced by inclusion of dietary defatted soybean meal (SBM), as this ingredient had been previously demonstrated to induce enteropathy in the distal intestine and reduce growth in salmon. Triplicate groups of Atlantic salmon were fed concentrations of 0, 100, 200 and 300 g kg(-1) SBM for 12 weeks and reduced growth performance was used as the indicator of nutritional stress. The transcriptome was analyzed in two tissues, liver and distal intestine, with the hypothesis being that the liver transcriptome would be characterized by gene expression responses related to overall growth and health performance, whereas intestinal gene expression would be dominated by specific responses to SBM. A set of 133 genes was differentially expressed in liver including 44 genes in common with the intestinal response. The liver-specific response included up-regulation of genes involved in protein digestion, energy metabolism and immune functions, whereas genes in other metabolic pathways were generally anabolic and down-regulated. These responses may be more related to general nutritional stress than to SBM per se. The transcriptomic profile in the distal intestine was consistent with the enteritis response as described previously. This study provides a comprehensive report on the profiles of liver and distal intestine transcriptomes, specifically highlighting the role of the liver in fish undergoing SBM-induced nutritional stress.

  12. Exogenous application of estradiol to eggs unexpectedly induces male development in two turtle species with temperature-dependent sex determination.

    PubMed

    Warner, Daniel A; Addis, Elizabeth; Du, Wei-guo; Wibbels, Thane; Janzen, Fredric J

    2014-09-15

    Steroid hormones affect sex determination in a variety of vertebrates. The feminizing effects of exposure to estradiol and the masculinizing effects of aromatase inhibition during development are well established in a broad range of vertebrate taxa, but paradoxical findings are occasionally reported. Four independent experiments were conducted on two turtle species with temperature-dependent sex determination (Chrysemys picta and Chelydra serpentina) to quantify the effects of egg incubation temperature, estradiol, and an aromatase inhibitor on offspring sex ratios. As expected, the warmer incubation temperatures induced female development and the cooler temperatures produced primarily males. However, application of an aromatase inhibitor had no effect on offspring sex ratios, and exogenous applications of estradiol to eggs produced male offspring across all incubation temperatures. These unexpected results were remarkably consistent across all four experiments and both study species. Elevated concentrations of estradiol could interact with androgen receptors or inhibit aromatase expression, which might result in relatively high testosterone concentrations that lead to testis development. These findings add to a short list of studies that report paradoxical effects of steroid hormones, which addresses the need for a more comprehensive understanding of the role of sex steroids in sexual development.

  13. 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.

  14. Urinary hydroxypyrene and estradiol in an occupationally exposed "outdoor" population.

    PubMed

    Sancini, A; Montuori, L; Chighine, A; Caciari, T; Giubilati, R; Sacco, C; Ponticiello, B G; Samperi, I; Tomei, G; Tomei, F; Rosati, M V

    2014-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are widely present in the air pollution. The urinary hydroxypyrene (1-HOPu) is considered the main biological biomarker currently available to measure the exposure to PAH. It is supposed responsible of an increase of estradiol levels in males. Aim of this study is to verify whether there is a relation between 1-HOPu and plasmatic estradiol in non-smoker male workers. The study was conducted on a sample of 122 non-smoker policemen in a large Italian city; we monitored their levels of 1-HOPu and the values of estradiol. The sample was divided into three groups according to the levels of urinary hydroxypyrene. The indices of correlation (r) and multiple linear regression (β), between levels of 1-HOPu and estradiol were calculated. It was also calculated the student's t-test among the groups to check the differences. We found statistically significant correlations and multivariate linear regressions between 1-HOPu and estradiol in the total sample and in group III (levels of 1-HOPu above the 75th percentile). The average levels of estradiol in group III was statistically and significantly higher than in the group I (levels of 1-HOPu below the 25th percentile) and group II (levels 1-HOPu between 25th and the 75th percentile). 1-HOPu in non-smoker male workers is related with an increase of plasmatic estradiol. We believe that PAHs, of which 1-HOPu is the main biomarker, can interact with the hypothalamic-pituitary axis. The preliminary results suggest that the topic needs further research on male and female as well.

  15. 17β-Estradiol enhances sulforaphane cardioprotection against oxidative stress.

    PubMed

    Angeloni, Cristina; Teti, Gabriella; Barbalace, Maria Cristina; Malaguti, Marco; Falconi, Mirella; Hrelia, Silvana

    2017-01-12

    The lower incidence of ischemic heart disease in female with respect to male gender suggests the possibility that female sex hormones could have specific effects in cardiovascular protection. 17β-Estradiol is the predominant premenopausal circulating form of estrogen and has a protective role on the cardiovascular system. Recent evidences suggest that gender can influence the response to cardiovascular medications; therefore, we hypothesized that sex hormones could also modulate the cardioprotective effects of nutraceutical compounds, such as the isothiocyanate sulforaphane, present in Brassica vegetables. This study was designed to explore the protective effects of sulforaphane in the presence of 17β-estradiol against H2O2-induced oxidative stress in primary cultures of rat cardiomyocytes. Interestingly, 17β-estradiol enhanced sulforaphane protective activity against H2O2-induced cell death with respect to sulforaphane or 17β-estradiol alone as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl-tetrazolium bromide and lactate dehydrogenase assays. Moreover, 17β-estradiol boosted sulforaphane ability to counteract oxidative stress, reducing intracellular reactive oxygen species and 8-hydroxy-2'-deoxyguanosine levels and increasing the expression of phase II enzymes. Using specific antagonists of estrogen receptor α and β, we observed that these effects are not mediated by estrogen receptors. Otherwise, ERK1/2 and Akt signaling pathways seem to be involved, as the presence of specific inhibitors of these kinases reduced the protective effect of sulforaphane in the presence of 17β-estradiol. Sulforaphane and 17β-estradiol co-treatment counteracted cell morphology alterations induced by H2O2 as evidenced by transmission electron microscopy. Our results demonstrated, for the first time, that estrogens could enhance sulforaphane protective effects, suggesting that nutraceutical efficacy might be modulated by sex hormones.

  16. Modulation of vitellogenin synthesis through estrogen receptor beta-1 in goldfish (Carassius auratus) juveniles exposed to 17-{beta} estradiol and nonylphenol

    SciTech Connect

    Soverchia, L.; Ruggeri, B.; Palermo, F.; Mosconi, G.; Cardinaletti, G.; Scortichini, G.; Gatti, G.; Polzonetti-Magni, A.M. . E-mail: alberta.polzonetti@unicam.it

    2005-12-15

    Many synthetic chemicals, termed xenoestrogens, have been shown to interact as agonists with the estrogen receptor (ER) to elicit biological responses similar to those of natural hormones. To date, the regulation of vitellogenesis in oviparous vertebrates has been widely used for evaluation of estrogenic effects. Therefore, Carassius auratus juveniles were chosen as a fish model for studying the effects of estradiol-17{beta} and different concentrations (10{sup -6} and 10{sup -7} M) of 4-nonylphenol (4-NP) on the expression of liver ER{beta}-1 subtype; plasma vitellogenin and sex steroids (androgens and estradiol-17{beta}) were also evaluated together with the bioaccumulation process, through mass-spectrometry. C. auratus is a species widespread in the aquatic environment and, on the toxicological point of view, can be considered a good 'sentinel' species. Juveniles of goldfish were maintained in tanks with only tap water or water with different concentrations (10{sup -6} and 10{sup -7} M) of 4-nonylphenol (4-NP), or 10{sup -7} M of estradiol-17{beta}. After 3 weeks of treatment, animals were anesthetized within 5 min after capture, and blood was immediately collected into heparinized syringes by cardiac puncture and stored at -70 deg. C; the gonads were fixed, then frozen and stored at -70 deg. C; the whole fish, liver, and muscle tissues were harvested and immediately stored at -70 deg. C for molecular biology experiments and bioaccumulation measurements. The estrogenic effects of 4-NP were evidenced by the presence of plasma vitellogenin in juveniles exposed both to estradiol-17{beta} and the two doses of 4-NP; moreover, exposure to 4-NP also increased aromatization of androgens, as suggested by decreasing androgens and increasing estradiol-17{beta} plasma levels. The changes of these parameters were in agreement with the increasing transcriptional rate of ER{beta}-1 mRNA in the liver, demonstrating that both estradiol-17{beta} and 4-NP modulate the vitellogenin

  17. Glucomannan- and glucomannan plus spirulina-enriched pork affect liver fatty acid profile, LDL receptor expression and antioxidant status in Zucker fa/fa rats fed atherogenic diets

    PubMed Central

    González-Torres, Laura; Matos, Cátia; Vázquez-Velasco, Miguel; Santos-López, Jorge A.; Sánchez-Martínez, Iria; García–Fernández, Camino; Bastida, Sara; Benedí, Juana; Sánchez-Muniz, Francisco J.

    2017-01-01

    ABSTRACT We evaluated the effects of glucomannan or glucomannan plus spirulina-restructured pork (RP) on liver fatty acid profile, desaturase/elongase enzyme activities and oxidative status of Zucker fa/fa rats for seven weeks. Control (C), glucomannan (G) and glucomannan/spirulina (GS)-RP; HC (cholesterol-enriched control), HG and HGS (cholesterol-enriched glucomannan and glucomannan/spirulina-RP) experimental diets were tested. Increased metabolic syndrome markers were found in C, G and GS rats. Cholesterol feeding increased liver size, fat, and cholesterol and reduced antioxidant enzyme levels and expressions. Cholesterolemia was lower in HG and HGS than in HC. GS vs. G showed higher stearic but lower oleic levels. SFA and PUFA decreased while MUFA increased by cholesterol feeding. The arachidonic/linoleic and docosahexaenoic/alpha-linolenic ratios were lower in HC, HG, and HGS vs. C, G, and GS, respectively, suggesting a delta-6-elongase-desaturase system inhibition. Moreover, cholesterol feeding, mainly in HGS, decreased low-density-lipoprotein receptor expression and the delta-5-desaturase activity and increased the delta-9-desaturase activity. In conclusion, the liver production of highly unsaturated fatty acids was limited to decrease their oxidation in presence of hypercholesterolaemia. Glucomannan or glucomannan/spirulina-RP has added new attributes to their functional properties in meat, partially arresting the negative effects induced by high-fat-high-cholesterol feeding on the liver fatty acid and antioxidant statuses. PMID:28325998

  18. Glucomannan- and glucomannan plus spirulina-enriched pork affect liver fatty acid profile, LDL receptor expression and antioxidant status in Zucker fa/fa rats fed atherogenic diets.

    PubMed

    González-Torres, Laura; Matos, Cátia; Vázquez-Velasco, Miguel; Santos-López, Jorge A; Sánchez-Martínez, Iria; García-Fernández, Camino; Bastida, Sara; Benedí, Juana; Sánchez-Muniz, Francisco J

    2017-01-01

    We evaluated the effects of glucomannan or glucomannan plus spirulina-restructured pork (RP) on liver fatty acid profile, desaturase/elongase enzyme activities and oxidative status of Zucker fa/fa rats for seven weeks. Control (C), glucomannan (G) and glucomannan/spirulina (GS)-RP; HC (cholesterol-enriched control), HG and HGS (cholesterol-enriched glucomannan and glucomannan/spirulina-RP) experimental diets were tested. Increased metabolic syndrome markers were found in C, G and GS rats. Cholesterol feeding increased liver size, fat, and cholesterol and reduced antioxidant enzyme levels and expressions. Cholesterolemia was lower in HG and HGS than in HC. GS vs. G showed higher stearic but lower oleic levels. SFA and PUFA decreased while MUFA increased by cholesterol feeding. The arachidonic/linoleic and docosahexaenoic/alpha-linolenic ratios were lower in HC, HG, and HGS vs. C, G, and GS, respectively, suggesting a delta-6-elongase-desaturase system inhibition. Moreover, cholesterol feeding, mainly in HGS, decreased low-density-lipoprotein receptor expression and the delta-5-desaturase activity and increased the delta-9-desaturase activity. In conclusion, the liver production of highly unsaturated fatty acids was limited to decrease their oxidation in presence of hypercholesterolaemia. Glucomannan or glucomannan/spirulina-RP has added new attributes to their functional properties in meat, partially arresting the negative effects induced by high-fat-high-cholesterol feeding on the liver fatty acid and antioxidant statuses.

  19. miR-29c suppresses pancreatic cancer liver metastasis in an orthotopic implantation model in nude mice and affects survival in pancreatic cancer patients.

    PubMed

    Zou, Yongkang; Li, Jianwei; Chen, Zhiyu; Li, Xiaowu; Zheng, Shuguo; Yi, Dong; Zhong, Ai; Chen, Jian

    2015-06-01

    We investigated mechanisms of pancreatic cancer metastasis and defined the biological role of miR-29c in pancreatic cancer metastasis. After two rounds of cell selection in vivo, pancreatic cancer cells with various metastatic potentials derived from spontaneous liver metastases were used as a model of pancreatic cancer to determine the role of miR-29c in pancreatic cancer metastasis. Pancreatic cancer samples were analyzed for miRNA-29c expression, and these levels were associated with survival between groups. miR-29c suppresses cell migration and invasion by targeting the MMP2 3'UTR. Overexpression of miR-29c suppresses pancreatic cancer liver metastasis in a nude mouse orthotopic implantation model. miR-29c expression was associated with metastasis and pancreatic cancer patient survival. miR-29c plays an important role in mediating pancreatic cancer metastasis to the liver by targeting MMP2. Therefore, miR-29c may serve as a novel marker of pancreatic cancer metastasis and possibly as a therapeutic target to treat pancreatic cancer liver metastasis.

  20. Possible role of resveratrol targeting estradiol and neprilysin pathways in lipopolysaccharide model of Alzheimer disease.

    PubMed

    El-Sayed, Nesrine S; Bayan, Yasmeen

    2015-01-01

    Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative brain disease that slowly destroys memory and thinking skills. It is the most common cause of dementia among older people. One of the most important hallmarks of AD is the presence of amyloid beta (Aβ) peptide in the brain that suggests that it is the primary trigger for neuronal loss. Herbal extracts have been studied over the years for their potential therapeutic effect in AD. Resveratrol (RSV), one of the most important phytoestrogens, is considered to be useful as estrogen plays an important role in AD. One of the most important amyloid degrading enzymes is neprilysin (NEP), which plays a major role in degrading Aβ, and mainly affected by estrogen. So, the aim of the present study is investigating the possible role of resveratrol in lipopolysaccharide model of AD and the implication of its possible role in regulating the estradiol and neprilysin pathways. Mice were divided into four groups: Control group (0.9 % saline), LPS group (0.8 mg/kg i.p once), Treatment group with RSV (mice were once injected with LPS then after 30 min given a dose of {4 mg/kg} RSV for 7 days), and RSV group only (mice received 4 mg/kg i.p for 7 days only). After 7 days mice were subjected to different behavioral tests using Y-maze, object recognition test, and open field tests. Estradiol and NEP level were measured using ELISA kit. Results showed RSV was able to reverse the decline in different types of memory (working, nonspatial, and locomotor functions) caused by LPS induction in mice. Moreover RSV was able to significantly increase both the estradiol level and NEP level and that may have a great role to decrease Aβ deposition as it has been confirmed that there is a link between NEP and estradiol level; by upregulation of estradiol level this consequently leads to increase in the level of NEP level, and by increasing the NEP level in brain, this lead to decrease in Aβ deposition and enhancing its

  1. Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently.

    PubMed

    Lau, Christine Li Ling; Chan, Sook Tyng; Selvaratanam, Manimegahlai; Khoo, Hui Wen; Lim, Adeline Yi Ling; Modamio, Pilar; Mariño, Eduardo L; Segarra, Ignacio

    2015-08-01

    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P < 0.05), was higher in liver and brain (P < 0.001), and lower in kidney (P < 0.001) vs. male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P < 0.01), brain, liver, and kidney (all P < 0.001). However, in male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P < 0.001). The tissue-to-plasma AUC0→∞ ratio was similar between male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P < 0.001) while remained unchanged in female mice and in kidney (male and female mice) but decreased 55% in brain (P < 0.05). The tissue-to-plasma partial AUC ratio, the drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences.

  2. Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation.

    PubMed

    Shi, Jian; Wang, Xinwen; Nguyen, Jenny; Wu, Audrey H; Bleske, Barry E; Zhu, Hao-Jie

    2016-04-01

    Sacubitril was recently approved by the Food and Drug Administration for use in combination with valsartan for the treatment of patients with heart failure with reduced ejection fraction. As a prodrug, sacubitril must be metabolized (hydrolyzed) to its active metabolite sacubitrilat (LBQ657) to exert its intended therapeutic effects. Thus, understanding the determinants of sacubitril activation will lead to the improvement of sacubitril pharmacotherapy. The objective of this study was to identify the enzyme(s) responsible for the activation of sacubitril, and determine the impact of genetic variation on sacubitril activation. First, an incubation study of sacubitril with human plasma and the S9 fractions of human liver, intestine, and kidney was conducted. Sacubitril was found to be activated by human liver S9 fractions only. Moreover, sacubitril activation was significantly inhibited by the carboxylesterase 1 (CES1) inhibitor bis-(p-nitrophenyl) phosphate in human liver S9. Further incubation studies with recombinant human CES1 and carboxylesterase 2 confirmed that sacubitril is a selective CES1 substrate. The in vitro study of cell lines transfected with wild-type CES1 and the CES1 variant G143E (rs71647871) demonstrated that G143E is a loss-of-function variant for sacubitril activation. Importantly, sacubitril activation was significantly impaired in human livers carrying the G143E variant. In conclusion, sacubitril is selectively activated by CES1 in human liver. The CES1 genetic variant G143E can significantly impair sacubitril activation. Therefore, CES1 genetic variants appear to be an important contributing factor to interindividual variability in sacubitril activation, and have the potential to serve as biomarkers to optimize sacubitril pharmacotherapy.

  3. Sodium-Glucose Cotransporter 2 Inhibitor and a Low Carbohydrate Diet Affect Gluconeogenesis and Glycogen Content Differently in the Kidney and the Liver of Non-Diabetic Mice

    PubMed Central

    Atageldiyeva, Kuralay; Fujita, Yukihiro; Yanagimachi, Tsuyoshi; Mizumoto, Katsutoshi; Takeda, Yasutaka; Honjo, Jun; Takiyama, Yumi; Abiko, Atsuko; Makino, Yuichi; Haneda, Masakazu

    2016-01-01

    A low carbohydrate diet (LCHD) as well as sodium glucose cotransporter 2 inhibitors (SGLT2i) may reduce glucose utilization and improve metabolic disorders. However, it is not clear how different or similar the effects of LCHD and SGLT2i are on metabolic parameters such as insulin sensitivity, fat accumulation, and especially gluconeogenesis in the kidney and the liver. We conducted an 8-week study using non-diabetic mice, which were fed ad-libitum with LCHD or a normal carbohydrate diet (NCHD) and treated with/without the SGLT-2 inhibitor, ipragliflozin. We compared metabolic parameters, gene expression for transcripts related to glucose and fat metabolism, and glycogen content in the kidney and the liver among the groups. SGLT2i but not LCHD improved glucose excursion after an oral glucose load compared to NCHD, although all groups presented comparable non-fasted glycemia. Both the LCHD and SGLT2i treatments increased calorie-intake, whereas only the LCHD increased body weight compared to the NCHD, epididimal fat mass and developed insulin resistance. Gene expression of certain gluconeogenic enzymes was simultaneously upregulated in the kidney of SGLT2i treated group, as well as in the liver of the LCHD treated group. The SGLT2i treated groups showed markedly lower glycogen content in the liver, but induced glycogen accumulation in the kidney. We conclude that LCHD induces deleterious metabolic changes in the non-diabetic mice. Our results suggest that SGLT2i induced gluconeogenesis mainly in the kidney, whereas for LCHD it was predominantly in the liver. PMID:27327650

  4. Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation

    PubMed Central

    Shi, Jian; Wang, Xinwen; Nguyen, Jenny; Wu, Audrey H.; Bleske, Barry E.

    2016-01-01

    Sacubitril was recently approved by the Food and Drug Administration for use in combination with valsartan for the treatment of patients with heart failure with reduced ejection fraction. As a prodrug, sacubitril must be metabolized (hydrolyzed) to its active metabolite sacubitrilat (LBQ657) to exert its intended therapeutic effects. Thus, understanding the determinants of sacubitril activation will lead to the improvement of sacubitril pharmacotherapy. The objective of this study was to identify the enzyme(s) responsible for the activation of sacubitril, and determine the impact of genetic variation on sacubitril activation. First, an incubation study of sacubitril with human plasma and the S9 fractions of human liver, intestine, and kidney was conducted. Sacubitril was found to be activated by human liver S9 fractions only. Moreover, sacubitril activation was significantly inhibited by the carboxylesterase 1 (CES1) inhibitor bis-(p-nitrophenyl) phosphate in human liver S9. Further incubation studies with recombinant human CES1 and carboxylesterase 2 confirmed that sacubitril is a selective CES1 substrate. The in vitro study of cell lines transfected with wild-type CES1 and the CES1 variant G143E (rs71647871) demonstrated that G143E is a loss-of-function variant for sacubitril activation. Importantly, sacubitril activation was significantly impaired in human livers carrying the G143E variant. In conclusion, sacubitril is selectively activated by CES1 in human liver. The CES1 genetic variant G143E can significantly impair sacubitril activation. Therefore, CES1 genetic variants appear to be an important contributing factor to interindividual variability in sacubitril activation, and have the potential to serve as biomarkers to optimize sacubitril pharmacotherapy. PMID:26817948

  5. Feeding soy protein isolate and n-3 PUFA affects polycystic liver disease progression in a PCK rat model of autosomal polycystic kidney disease.

    PubMed

    Maditz, Kaitlin H; Benedito, Vagner A; Oldaker, Chris; Nanda, Nainika; Lateef, Sundus S; Livengood, Ryan; Tou, Janet C

    2015-04-01

    In polycystic liver disease (PCLD), multiple cysts cause liver enlargement, structural damage, and loss of function. Soy protein and dietary ω-3 polyunsaturated fatty acids (n-3 PUFAs) have been found to decrease cyst proliferation and inflammation in polycystic kidney disease. Therefore, the aim of the study was to investigate whether soy protein and n-3 PUFA supplementation attenuates PCLD. Young (age 28 days) female PCK rats were fed (n = 12 per group) either casein + corn oil (casein + CO), casein + soybean oil (casein + SO), soy protein isolate + soybean oil (SPI + SO), or SPI + 1:1 soybean/salmon oil blend (SPI + SB) diet for 12 weeks. Liver histology, gene expression by real-time quantitative polymerase chain reaction, and serum markers of liver injury were determined. Diet had no effect on PCLD progression as indicated by no significant differences in liver weight and hepatic proliferation gene expression between diet groups. PCK rats fed SPI + SB diet, however, had the greatest (P < 0.05) histological evidence of hepatic cyst obstruction, portal inflammation, steatosis, and upregulation (P = 0.03) of fibrosis-related genes. Rats fed SPI + SB diet also had the lowest (P < 0.001) serum cholesterol and higher (P < 0.05) serum alkaline phosphatase and bilirubin concentrations. Feeding young female PCK rats SPI and n-3 PUFA failed to attenuate PCLD progression. Furthermore, feeding SPI + SB diet resulted in complications of hepatic steatosis attributable to cysts obstruction of bile duct and hepatic vein. Based on the results, it was concluded that diet intervention alone was not effective at attenuating PCLD associated with autosomal recessive polycystic kidney disease.

  6. Dydrogesterone does not reverse the cardiovascular benefits of percutaneous estradiol.

    PubMed

    Kuba, V M; Teixeira, M A M; Meirelles, R M R; Assumpção, C R L; Costa, O S

    2013-02-01

    To evaluate the influence of dydrogesterone on estimated cardiovascular risk of users of hormone replacement therapy (HRT) (with percutaneous 17β-estradiol in monotherapy and in combination with dydrogesterone) and HRT non-users through the Framingham score tool for a period of 2 years. Framingham scores were calculated from the medical records of patients treated for at least 2 years with 17β-estradiol alone or in combination with dydrogesterone, along with HRT non-users, through the analysis of patient medical records, followed for at least 2 years at Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione. Improvements in lipid profile, glucose and blood pressure levels, which reduced the estimated cardiovascular risk, were observed in the 17β-estradiol group. Similar changes were observed in the users of 17β-estradiol + dydrogesterone, suggesting that this progestogen does not attenuate the effects caused by 17β-estradiol. Both HRT groups showed a reduction in their Framingham score. In contrast to data from other HRT investigations on cardiovascular risk, these formulations proved to be safe, even in the first year of use.

  7. Incidence of Venous Thromboembolism in Transgender Women Receiving Oral Estradiol.

    PubMed

    Arnold, Justin D; Sarkodie, Eleanor P; Coleman, Megan E; Goldstein, Deborah A

    2016-11-01

    One of the most serious known adverse effects of feminizing cross-sex hormone therapy (CSHT) is venous thromboembolism (VTE); however, no study has assessed the incidence of VTE from the hormone therapies used in the United States because previous publications on this topic have originated in Europe. CSHT in the United States typically includes estradiol with the antiandrogen spironolactone, whereas in Europe estradiol is prescribed with the progestin cyproterone acetate. To estimate the incidence of VTE from the standard feminizing CSHTs used in the United States. A retrospective chart review of transgender women who had been prescribed oral estradiol at a District of Columbia community health center was performed. The primary outcomes of interest were deep vein thrombosis or pulmonary emboli. From January 1, 2008 through March 31, 2016, 676 transgender women received oral estradiol-based CSHT for a total of 1,286 years of hormone treatment and a mean of 1.9 years of CSHT per patient. Only one individual, or 0.15% of the population, sustained a VTE, for an incidence of 7.8 events per 10,000 person-years. There was a low incidence of VTE in this population of transgender women receiving oral estradiol. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  8. 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

  9. Cellular mechanisms of estradiol-mediated masculinization of the brain.

    PubMed

    Schwarz, Jaclyn M; McCarthy, Margaret M

    2008-04-01

    The sexual differentiation of reproductive physiology and behavior in the rodent brain is largely determined by estradiol aromatized from testicular androgens. The cellular mechanisms by which estradiol masculinizes the brain are beginning to emerge and revealing novel features of brain development that are highly region-specific. In the preoptic area, the major site controlling male sexual behavior, estradiol increases the level of the COX-2 enzyme and its product, prostaglandin E2 which promotes dendritic spine synaptogenesis. In the ventromedial nucleus of the hypothalamus, the major site controlling female reproductive behavior, estradiol promotes glutamate release from synaptic terminals, activating NMDA receptors and the MAP kinase pathway. In the arcuate nucleus, a major regulator of anterior pituitary function, estradiol increases GABA synthesis, altering the morphology of neighboring astrocytes and reducing formation of dendritic spines synapses. Glutamate, GABA and the importance of neuronal-astrocytic cross-talk are emerging as common aspects of masculinization. Advances are also being made in the mechanistic basis of female brain development, although the challenges are far greater.

  10. 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.

  11. 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

  12. Simultaneous Degradation of Estrone, 17β-Estradiol and 17α-Ethinyl Estradiol in an Aqueous UV/H₂O₂ System.

    PubMed

    Ma, Xiaoyan; Zhang, Chao; Deng, Jing; Song, Yali; Li, Qingsong; Guo, Yaping; Li, Cong

    2015-09-25

    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.

  13. The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-α production.

    PubMed

    Dimitrijević, Mirjana; Stanojević, Stanislava; Kuštrimović, Nataša; Mitić, Katarina; Vujić, Vesna; Aleksić, Iva; Radojević, Katarina; Leposavić, Gordana

    2013-11-01

    The phenotype and function of tissue macrophages substantially depend on the cellular milieu and biological effector molecules, such as steroid hormones, to which they are exposed. Furthermore, in female rats, aging is associated with the altered macrophage functioning and the increased estrogen level is followed by a decrease in that of progesterone. Therefore, the present study aimed to investigate the influence of estradiol/progesterone balance on rat macrophage function and phenotype throughout whole adult lifespan. We ovariectomized rats at the late prepubertal age or at the very end of reproductive lifespan, and examined the expression of ED2 (CD163, a marker of mature resident macrophages related to secretion of inflammatory mediators) on peritoneal macrophages and their ability to produce TNF-α and NO upon LPS-stimulation at different age points. In addition, to delineate direct and indirect effects of estrogen, we assessed the in vitro influence of different concentrations of 17β-estradiol on LPS-induced macrophage TNF-α and NO production. Results showed that: (a) the low frequency of ED2(high) cells amongst peritoneal macrophages of aged rats was accompanied with the reduced TNF-α, but not NO production; (b) estradiol level gradually increased following ovariectomy; (c) macrophage ED2 expression and TNF-α production were dependent on estradiol/progesterone balance and they changed in the same direction; (d) changes in estradiol/progesterone balance differentially affected macrophages TNF-α and NO production; and (e) estradiol exerted pro-inflammatory and anti-inflammatory effects on macrophages in vivo and in vitro, respectively. Overall, our study discloses that estradiol/progesterone balance contributes to the fine-tuning of rat macrophage secretory capacity, and adds to a better understanding of the ovarian steroid hormone role in the regulation of macrophage function, and its significance for the age-associated changes in innate immunity.

  14. 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).

  15. 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.

  16. 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.

  17. Macromolecular prodrugs. XIII. Hydrosoluble conjugates of 17β-estradiol and estradiol-17β-valerate with polyaspartamide polymer.

    PubMed

    Končič, Marijana Zovko; Zorc, Branka; Novak, Predrag

    2011-12-01

    Two hydrosoluble conjugates of 17β-estradiol (ED) and estradiol-17β-valerate (EV) with polyaspartamide polymer were prepared and characterized. ED and EV were first chemically modified and bound to poly[α,β-(N-2-hydroxyethyl-DL-aspartamide)]-poly[α,β-(N-2-aminoethyl-DL-aspartamide)] (PAHA), a hydrosoluble polyaspartamide-type copolymer bearing both hydroxyl and amino groups. ED was first converted to 17-hemisuccinate (EDS) and then bound to PAHA. In the resulting conjugate PAHA-EDS, the estradiol moiety was linked to the polymer through a 2-aminoethylhemisuccinamide spacer. On the other hand, EV was first converted to estradiol-17β-valerate-3-(benzotriazole-1-carboxylate), which readily reacted with amino groups in PAHA affording the polymer-drug conjugate PAHA-EV. In the prepared conjugate PAHA-EV, the estradiol moiety was covalently bound to the polyaspartamide backbone by carbamate linkage, through an ethylenediamine spacer. The polymer-drug conjugates were designed and prepared with the aim to increase water-solubility, bioavailability and to improve drug delivery of the lipophilic estrogen hormone.

  18. Progesterone resistance in endometriosis: link to failure to metabolize estradiol.

    PubMed

    Bulun, Serdar E; Cheng, You-Hong; Yin, Ping; Imir, Gonca; Utsunomiya, Hiroki; Attar, Erkut; Innes, Joy; Julie Kim, J

    2006-03-27

    Endometriosis is the most common cause of pelvic pain and affects an estimated 5 million women in the US. The biologically active estrogen estradiol (E2) is the best-defined mitogen for the growth and inflammation processes in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Progesterone and progestins may relieve pain by limiting growth and inflammation in endometriosis but a portion of patients with endometriosis and pelvic pain do not respond to treatment with progestins. Moreover, progesterone-induced molecular changes in the eutopic (intrauterine) endometrial tissue of women with endometriosis are either blunted or undetectable. These in vivo observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptors (PRs) and the lack of the PR isoform named progesterone receptor B (PR-B). In normal endometrium, progesterone acts on stromal cells to induce secretion of paracrine factor(s). These unknown factor(s) act on neighboring epithelial cells to induce the expression of the enzyme 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD-2), which metabolizes the biologically active estrogen E2 to estrone (E1). In endometriotic tissue, progesterone does not induce epithelial 17beta-HSD-2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate 17beta-HSD-2 may be due to the lack of PR-B and very low levels of progesterone receptor A (PR-A) observed in vivo in endometriotic tissue. The end result is deficient metabolism of E2 in endometriosis giving rise to high local concentrations of this local mitogen. The cellular and molecular mechanisms underlying progesterone resistance and failure to metabolize E2 in endometriosis are reviewed.

  19. Estradiol-progesterone interaction during the preparation of vaginal rings.

    PubMed

    Saleh, Saleh I; Khidr, Sayed H; Ahmed, Sayed M; Jackanicz, Theodore M; Nash, Harold A

    2003-02-01

    An unexpected enhanced release, in vitro, of estradiol (E2) was observed on the preparation of vaginal rings containing E2 and progesterone (P) in a silicone elastomer. The present work deals with exploring the reason(s) behind this enhanced E2 release. The effect of the ring design (i.e., putting P and E2 in the same compartment or in adjacent or separate compartments) was studied. The effects of the curing temperature as well as the curing time were also investigated. The possible interaction(s) between P and E2 on simple heating of their mixtures was investigated using infrared (IR), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR) techniques. Also, the dissolution behavior of P, E2, and their mixture before and after heating was studied. The ring design, with respect to the position of the steroid layer(s), affected the release of P and E2 from the vaginal rings. Curing the rings at higher temperatures (>/=140 degrees C) for >/=30 min resulted in an enhanced release of the steroids, especially E2. The IR, DSC, phase diagram, and NMR results indicate that an interaction between P and E2, leading to the formation of a molecular complex, took place. It was concluded that putting P and E2 in the same compartment and curing by heating at a high temperature and for an extended time promoted this kind of interaction. The greater hydrophobicity of the interaction product, relative to that of E2, was considered the main reason behind the enhanced in vitro release of E2 from the vaginal rings.

  20. Multiple same day cryolipolysis treatments for the reduction of subcutaneous fat are safe and do not affect serum lipid levels or liver function tests.

    PubMed

    Klein, Kenneth B; Bachelor, Eric P; Becker, Edward V; Bowes, Leyda E

    2017-09-01

    Cryolipolysis is a safe and effective non-surgical procedure for reducing subcutaneous fat. It spares adjacent structures, is associated with few adverse events, and is well-tolerated by patients. Previous studies involving one or two simultaneous treatment sites have shown no effect on serum lipid levels or liver tests. The purpose of this study was to determine whether multiple same day treatments (abdomen plus both flanks) result in changes in these blood tests, and is safe. Thirty-five adult males and females underwent same-day cryolipolysis (CoolSculpting System, ZELTIQ Aesthetics) of the lower abdomen and flanks for reduction of subcutaneous fat. Serum lipids and liver tests were measured prior to treatment and at 1, 4, and 12 weeks post-treatment. Expected treatment side-effects were assessed immediately post-treatment and at the 12-week follow-up visit. Adverse events were also monitored. Treatment consisted of one cycle to the lower abdomen using a large vacuum applicator and simultaneous treatment of both flanks, one cycle each, with medium vacuum applicators .Time between the abdomen and flanks procedures was not to exceed 30 minutes. The procedures were well-tolerated by patients; expected treatment effects were in general mild or moderate, and resolved without intervention. There were no clinically meaningful changes from baseline to any subsequent time point in any serum lipid test. This was also true for all liver tests. There were no treatment-related adverse events. Multiple cycle, same day cryolipolysis treatment of the lower abdomen and both flanks is well-tolerated and safe. It does not lead to changes in serum lipids or liver tests at any of the measured time points following the procedure. Lasers Surg. Med. 49:640-644, 2017. © 2017 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals Inc. © 2017 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals Inc.

  1. Nonalcoholic fatty liver disease and alteration in semen quality and reproductive hormones.

    PubMed

    Li, Yan; Liu, Lei; Wang, Bin; Chen, Dongfeng; Wang, Jun

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the world. Some reports have shown that NAFLD may cause multisystem damage, but its influence on male reproductive function has rarely been studied. To evaluate the influence of NAFLD on sperm quality and reproductive hormones in Chinese men. A total of 102 NAFLD men and 94 healthy men without fatty liver (control) were enrolled in this study. All participants underwent a physical examination, and were subjected to lifestyle questionnaires and abdominal ultrasound examination. The semen quality (volume, concentration, motility, and morphology) and serum hormonal levels (testosterone, estradiol, follicle-stimulating hormone, inhibin B, sex hormone-binding globulin, and luteinizing hormone) were examined and compared between the two groups. The levels of serum testosterone and sex hormone-binding globulin were significantly lower in the NAFLD patients compared with the control group. Sperm concentration (P=0.04), sperm count (P=0.01), and total motility (P=0.03) in the NAFLD patients were significantly decreased compared with the control group. However, no significant differences were observed in semen volume and morphology. Multivariate analysis showed that sperm concentration, sperm count, and motility were significantly associated with NAFLD and abstinence (P<0.05 or P<0.001). These results suggest that NAFLD could significantly affect sperm quality and reproductive hormones.

  2. Estradiol modulates effort-based decision making in female rats.

    PubMed

    Uban, Kristina A; Rummel, Julia; Floresco, Stan B; Galea, Liisa A M

    2012-01-01

    Disorders of the dopamine system, such as schizophrenia or stimulant addiction, are associated with impairments in different forms of cost/benefit decision making. The neural circuitry (ie amygdala, prefrontal cortex, nucleus accumbens) underlying these functions receives dopamine input, which is thought to have a central role in mediating cost/benefit decisions. Estradiol modulates dopamine activity, and estrogen receptors (ERs) are found within this neurocircuitry, suggesting that decision making may be influenced by estradiol. The present study examined the contribution of estradiol and selective ERα and β agonists on cost/benefit decision making in adult female Long-Evans rats. An effort-discounting task was utilized, where rats could either emit a single response on a low-reward lever to receive two pellets, or make 2, 5, 10, or 20 responses on a high-reward lever to obtain four pellets. Ovariectomy increased the choice on the high-reward lever, whereas replacement with high (10 μg), but not low (0.3 μg), levels of estradiol benzoate reduced the choice on the high-reward lever. Interestingly, both an ERα agonist (propyl-pyrazole triol (PPT)) and an ERβ agonist (diarylpropionitrile (DPN)) increased choice on the high-reward lever when administered independently, but when these two agonists were combined, a decrease in choice for the high-reward lever was observed. The effects of estradiol, PPT, and DPN were more pronounced 24 h post-administration, suggesting that these effects may be genomic in nature. Together, these results demonstrate that estradiol modulates cost/benefit decision making in females, whereby concomitant activation of ERα and β receptors shifts the decision criteria and reduces preference for larger, yet more costly rewards.

  3. [Liver involvement in lymphogranulomatosis].

    PubMed

    Hanke, P; Sickel, W; Stenzel, L; Krug, K; Roedel, G; Rath, F W

    1979-07-15

    Of 146 patients with lymphogranulomatosis biochemical parameters were tested for their diagnostic valency concerning the recognition of a liver infiltration. In patients with histologically proved affection of the liver the AP, GGTP, AAP, LAP and LDH show a significant increase in comparison to the enzyme values of the patients without any hepatic manifestation. In an increased result of 4 enzyme values with a probability of 85% muste be reckoned with a participation of the liver. The enzyme SGOT, SGPT, GDH, LDH-isoenzymes, choline esterase, beta-GC, the De Ritis quotient and the quotient (Formula: see text), on the other hand, do not give any additional differential-diagnostic information.

  4. Liver Immunology

    PubMed Central

    Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

    2014-01-01

    The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

  5. Experimental Hepatotoxicity Produced by Ethinyl estradiol

    PubMed Central

    Pandey, Govind; Pandey, S. P.; Sharma, Madhuri

    2011-01-01

    Ethinyl oestradiol (EO) is the most commonly used as a component of oral contraceptive and hormonal replacement therapy (HRT) in women. However, its excessive and prolonged use may cause cytotoxicity, including cancer of many organs. Hence, the present study was performed to produce the experimental hepatotoxicity in female albino rats. EO was administered to different groups of rats, respectively @ 250, 500 and 750 μg/kg body weight, orally, weekly for 16 and 20 weeks. One group of rats was administered with saline alone to serve as control. The rats were sacrificed after their respective experimental periods, and the livers were collected and preserved in 10% buffered formalin. Later on, the histopathological study of liver tissues was done. On the 17th week, the hepatic tissues showed severe congestion, focal areas of hemorrhage, extreme vacuolation of cytoplasm, distended sinusoids with dilated central veins. Degeneration and necrosis of hepatocytes as evidenced by increased cytoplasmic granularity, and dissolution of nuclear materials were seen. On the 21st weeks, these changes were extremely severe and quite conspicuous. Distinct fibrosis was also noticed. EO caused hepatotoxicity, the extent and severity of which were dose and time dependent, indicating that this drug at higher dose after prolonged duration (500 or 750 μg/kg, orally, weekly for 20 weeks) may cause the standard experimental hepatotoxicity in rats. PMID:21976823

  6. ESTRADIOL AND OSMOLALITY: BEHAVIORAL RESPONSES AND CENTRAL PATHWAYS

    PubMed Central

    Curtis, Kathleen S.

    2015-01-01

    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. PMID:26074202

  7. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. delta 9-THC and 17-beta-estradiol in hippocampus.

    PubMed

    Foy, M R; Teyler, T J; Vardaris, R M

    1982-04-01

    Electrophysiological field potentials recorded from in vitro hippocampal slice preparations show dose-dependent differences in response to 17-beta-estradiol (E2) and delta-9-tetrahydrocannabinol (THC) added to the incubation medium. Using a wide range of doses (1 pM-10 nM), it was found that mid-range concentrations of estradiol (100 pM) and THC (10 pM) tended to increase field potentials in CA1 of rodents. Higher dose levels of each agent were found to depress neuronal activity. In the context of prior findings, these results suggest that the two compounds share a common mechanism of action in the hippocampus.

  9. Serotonin (5-HT) Affects Expression of Liver Metabolic Enzymes and Mammary Gland Glucose Transporters during the Transition from Pregnancy to Lactation

    PubMed Central

    Laporta, Jimena; Peters, Tonia L.; Merriman, Kathryn E.; Vezina, Chad M.; Hernandez, Laura L.

    2013-01-01

    The aim of this experiment was to demonstrate the ability of feeding serotonin (5-HT; 5-hydroxytryptamine) precursors to increase 5-HT production during the transition from pregnancy to lactation and the effects this has on maternal energy metabolism in the liver and mammary gland. Pregnant rats (n = 45) were fed one of three diets: I) control (CON), II) CON supplemented with 0.2% 5-hydroxytryptophan (5-HTP) or III) CON supplemented with 1.35% L-tryptophan (L-TRP), beginning on d13 of pregnancy through d9 of lactation (d9). Serum (pre and post-partum), milk (daily), liver and mammary gland tissue (d9) were collected. Serum 5-HT was increased in the 5-HTP fed dams beginning on d20 of gestation and remained elevated through d9, while it was only increased on d9 in the L-TRP fed dams. 5-HT levels were increased in mammary gland and liver of both groups. Additionally, 5-HTP fed dams had serum and milk glucose levels similar to the CON, while L-TRP had decreased serum (d9) and milk glucose (all dates evaluated). Feeding 5-HTP resulted in increased mRNA expression of key gluconeogenic and glycolytic enzymes in liver and glucose transporters 1 and 8 (GLUT-1, -8) in the mammary gland. We demonstrated the location of GLUT-8 in the mammary gland both in the epithelial and vascular endothelial cells. Finally, phosphorylated 5′ AMP-activated protein kinase (pAMPK), a known regulator of intracellular energy status, was elevated in mammary glands of 5-HTP fed dams. Our results suggest that increasing 5-HT production during the transition from pregnancy to lactation increases mRNA expression of enzymes involved in energy metabolism in the liver, and mRNA abundance and distribution of glucose transporters within the mammary gland. This suggests the possibility that 5-HT may be involved in regulating energy metabolism during the transition from pregnancy to lactation. PMID:23469086

  10. Liver disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the ...

  11. Liver Transplant

    MedlinePlus

    ... Trials Porphyria Primary Biliary Cholangitis Definition & Facts Symptoms & Causes Diagnosis Treatment Eating, Diet, & Nutrition Clinical Trials Primary Sclerosing Cholangitis Wilson Disease Liver Disease A-Z Liver Transplant View or ...

  12. Liver scan

    MedlinePlus

    ... cirrhosis or hepatitis ) Superior vena cava obstruction Splenic infarction (tissue death) Tumors Risks Radiation from any scan ... Hepatitis Liver cancer - hepatocellular carcinoma Liver disease Splenic infarction SVC obstruction Review Date 1/18/2015 Updated ...

  13. Effects of 17beta-estradiol and IGF-1 on L-type voltage-activated and stretch-activated calcium currents in cultured rat cortical neurons.

    PubMed

    Sánchez, Julio C; López-Zapata, Diego F; Pinzón, Oscar A

    2014-01-01

    Calcium transport pathways are key factors for understanding how changes in the cytoplasmic calcium concentration are associated with neuroprotection because calcium is involved in the onset of death signaling in neurons. This study characterized the effects of 17β-estradiol and IGF-1 on voltage-activated and stretch-activated calcium channels in rat cultured cortical neurons. The whole-cell patch-clamp technique, using a voltage steps protocol or by applying positive pressure into the micropipette, was used on 7-10 day cultured neurons from a Wistar rat cortex, and pharmacological characterization was performed on these neurons. Both 17β-estradiol and IGF-1 inhibited the currents mediated by L-type voltage-activated calcium channels, although the IGF-1 effects were lower than those of 17β-estradiol. The effect of both hormones together was greater than the sum of the effects of the individual agents. Unlike IGF-1, 17β-estradiol decreased the current mediated by stretch-activated channels. The inhibition of the classical receptors of these hormones did not affect the results. Both hormones regulate voltage-activated calcium channels in a synergistic way, but only 17β-estradiol has an inhibitory effect on stretch-activated calcium channels. These effects are not mediated by classical receptors and may be relevant to the neuroprotective effects of both hormones because they diminish calcium entry into the neuron and decrease the possibility for the onset of apoptotic signaling.

  14. Comprehensive analysis of lncRNAs and mRNAs in skeletal muscle of rainbow trout (Oncorhynchus mykiss) exposed to estradiol

    USDA-ARS?s Scientific Manuscript database

    Estradiol (E2) is a steroid hormone that negatively affects muscle growth in rainbow trout, but the mechanisms directing with this response are not fully understood. To better characterize the effects of E2 in muscle, we identified differentially regulated mRNAs and lncRNAs in juvenile rainbow trout...

  15. The effect of food on the bioavailability of norethindrone and ethinyl estradiol from norethindrone acetate/ethinyl estradiol tablets intended for continuous hormone replacement therapy.

    PubMed

    Boyd, Rebecca A; Zegarac, Elizabeth A; Eldon, Michael A

    2003-01-01

    As part of the development of a combination product containing norethindrone acetate and low-dose ethinyl estradiol for continuous hormone replacement therapy in postmenopausal women, a study was conducted to determine the effect of a high-fat meal on the bioavailability of norethindrone and ethinyl estradiol from tablets containing 1 mg norethindrone acetate/10 micrograms ethinyl estradiol. Eighteen healthy postmenopausal women participated in an open-label, single-dose, randomized, three-way crossover study in which 2 x 1/10 norethindrone acetate/ethinyl estradiol tablets were administered fasting and with a high-fat breakfast, and the same dose was administered in solution. Following each treatment, serial blood samples were collected for 48 hours, and plasma ethinyl estradiol and norethindrone concentrations were determined by a validated gas chromatography/mass spectrometry (GC/MS) method. Individual plasma ethinyl estradiol and norethindrone pharmacokinetic parameters were calculated by noncompartmental methods for each treatment and analyzed by ANOVA to obtain differences between least squares treatment mean values and associated 90% confidence intervals. Rates of ethinyl estradiol and norethindrone availability from tablets administered with food were slower than availability rates from tablets administered while fasting. Systemic exposure to ethinyl estradiol was unaffected by administration of tablets with food, whereas exposure to norethindrone increased by 27%. Because administration of norethindrone acetate/ethinyl estradiol 1/10 tablets with a high-fat meal did not decrease systemic exposure to norethindrone and ethinyl estradiol, this formulation can be taken without regard to meals.

  16. Liver Hemangioma

    MedlinePlus

    ... Make an appointment with your doctor if you experience any persistent signs and symptoms that worry you. Causes It's not clear what causes a liver hemangioma to form. Doctors believe liver hemangiomas are congenital — meaning that you're born with them. A liver ...

  17. Vaginal estradiol use and the risk for cardiovascular mortality.

    PubMed

    Mikkola, Tomi S; Tuomikoski, Pauliina; Lyytinen, Heli; Korhonen, Pasi; Hoti, Fabian; Vattulainen, Pia; Gissler, Mika; Ylikorkala, Olavi

    2016-04-01

    Does the use of post-menopausal vaginal estradiol (VE) affect the mortality risk for coronary heart disease (CHD) and stroke. The use of VE reduces the risk for cardiovascular mortality. A growing number of women use VE for post-menopausal genitourinary symptoms. Although this therapy is intended to have only local effects, estrogen is absorbed into the blood circulation and thus VE use may also have systemic effects. We studied a nationwide cohort in Finland 1994-2009 during which post-menopausal women (n = 195 756) initiated the use of VE (age [mean ± SD] 65.7 ± 10.9 years). Follow-up data gathered 1.4 million women-years and we assessed the mortality risk due to CHD (n= 9656) or stroke (n = 4294). The mortality risk in VE users was compared with that in the age-matched background population (standardized mortality ratio; [SMR]; 95% confidence interval) and related to various durations of exposure to VE (1 to ≤3, >3 to ≤5, >5 to ≤10 and >10 years). The use of VE was accompanied by decreases in the risk for CHD and stroke death. The risk reduction for CHD death was highest for >3 to ≤5 years exposure (SMR 0.64; 0.57-0.70) and for stroke for >5 to ≤10 years exposure (SMR 0.64; 0.57-0.72). The risk reductions for both CHD and stroke mortality were detected in all age groups with the highest risk reduction being in women aged 50-59 years (SMR 0.43; 0.19-0.88 and SMR 0.21; 0.06-0.58, respectively). Our series lack a placebo arm and thus, may harbor a healthy woman bias. Moreover, data on clinical variables such as weight, smoking, blood pressure and family background were unobtainable for this study. Women using both VE and systemic hormone therapy (HT) were included in the comparator background population. This should not cause any significant error because the proportion of women using VE or other HT was modest (<10% in age-matched population) and because the use of systemic HT also reduces death risks in the same population. Our data cannot be directly

  18. Effects of oral continuous and transdermal cyclic 17-beta estradiol and norethindrone acetate replacement therapy on platelet aggregation in postmenopausal women.

    PubMed

    Kaplan, Petek Balkanli; Gücer, Fatih; Sayin, N Cenk; Yüce, M Ali; Yardim, Turgut

    2002-08-01

    To evaluate the effects of an oral continuous and transdermal cyclic 17-beta estradiol and norethindrone acetate combination on platelet aggregation in post-menopausal women. Fifty postmenopausal women were randomly assigned to receive 17-beta estradiol and norethindrone acetate either orally continuously or transdermally cyclically and sequentially. Platelet counts and maximum platelet aggregation rates were measured before and after three months treatment. At three months there were no significant changes in platelet counts or in adenosine diphosphate-induced or epinephrine-induced platelet aggregation rates in either treatment group. Hormone replacement treatment with a 17-beta estradiol and norethindrone acetate combination either orally continuously or transdermally cyclically and sequentially does not affect platelet aggregation in postmenopausal women.

  19. 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

  20. Endometriosis Under Estradiol Stimulation Imaged Using 18F-FDG and Its Control After Estradiol Cessation and Progesterone Hormonal Replacement.

    PubMed

    Arsenault, Frédéric; Turcotte, Éric

    2016-03-01

    Endometriosis is a frequent and benign cause of disabling abdominal pain, for which a diagnosis suspicion is clinically raised, but its confirmation necessitates a surgical exploration by laparoscopy. Foci of endometriosis proliferate under estrogen stimulation, like normal endometrium. We present a patient under estradiol stimulation for a history of endometrial cancer who underwent a PET/CT scan to assess an abdominal lesion showing a high F-FDG uptake, which normalized under progesterone hormonal replacement and cessation of estradiol. Two consecutive biopsies confirmed endometriosis. F-FDG evaluation of endometriosis under estrogen stimulation could be a promising approach to refractory endometriosis assessment.

  1. 9(10 leads to 19)abeo steriods. Total synthesis of abeo-estradiol, abeo-estradiol 3-methyl ether, and 17 alpha-ethynyl abeo-estradiol 3-methyl ether.

    PubMed

    Abushanab, E; Lee, D Y; Meresak, W A; Duax, W L

    1976-04-30

    Total synthesis of abeo-estradiol, abeo-estradiol 3-methyl ether, and 17alpha-ethynyl abeo-estradiol 3-methyl ether is described. Stereochemical assignments in 9(10 through 19) abeo-estradiol and its 3-methyl ether were made by X-ray analysis of the 17-keytone. Single crystals were grown by evaporation of a petroleum ether-ethanol solution and the intensities of 2619 diffraction spectra were measured, of which 1036 had intensity greater than twice the background. The structure was refined by full-matrix least-squares techniques and all hydrogen atoms were located in the Fourier difference syntheses.

  2. Chronic administration of saturated fats and fructose differently affect SREBP activity resulting in different modulation of Nrf2 and Nlrp3 inflammasome pathways in mice liver.

    PubMed

    Nigro, Debora; Menotti, Francesca; Cento, Alessia S; Serpe, Loredana; Chiazza, Fausto; Dal Bello, Federica; Romaniello, Francesco; Medana, Claudio; Collino, Massimo; Aragno, Manuela; Mastrocola, Raffaella

    2017-04-01

    The overconsumption of both saturated fats and fructose in the modern society has been related to the development of nonalcoholic fatty liver disease (NAFLD). However, the specific contribution of individual dietary components on the progression of NAFLD to nonalcoholic steatohepatitis (NASH) has been poorly investigated. Therefore, the aim of our study was to investigate the dissimilar effects of these two dietary components on selected proinflammatory and antioxidant pathways in the liver of C57BL/6 mice fed a standard (SD), a 45% saturated fat (HFAT) or a 60% fructose (HFRT) diet for 12 weeks. HFAT diet evoked systemic metabolic alterations and overweight, not observed in HFRT mice. However, HFRT mice had a greater hepatic triglyceride deposition with increased ratio of triacylglycerols containing the palmitic acid compared to HFAT, as assessed by liquid chromatography-mass spectrometry analysis. This effect is due to the higher activation of the SCAP/SREBP1c lipogenic pathway by HFRT feeding. In addition, we found inhibition of Keap1/Nrf2 antioxidant signaling and more robust stimulation of the Nlrp3 inflammasome pathway in the livers of HFRT-fed mice when compared with HFAT-fed mice, which is consistent with the recent finding that palmitate and SREBP1c are implicated in hepatic oxidative stress and inflammation. These effects were associated with increased hepatic inflammation, as confirmed by high expression of markers of leukocyte infiltration in the HFRT group. Thus, we hypothesize an amplifying loop among lipogenesis, palmitate, Nrf2 and Nlrp3 that leads to a higher risk of NAFLD progression to NASH in a high-fructose diet compared to a high-saturated fat intake. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Alcoholic liver disease: The gut microbiome and liver crosstalk

    PubMed Central

    Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

    2015-01-01

    Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier or preventing cellular responses to microbial products protect from experimental alcoholic liver disease. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of alcoholic liver disease. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship and consequences for alcoholic liver disease. We also discuss how the liver affects the intestinal microbiota. PMID:25872593

  4. 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

  5. Studies on the Liver to Kidney Switch of Erythropoietin Production

    PubMed Central

    Zanjani, Esmail D.; Ascensao, Joao L.; McGlave, Philip B.; Banisadre, Mussa; Ash, Robert C.

    1981-01-01

    Although the liver is the major site of erythropoietin (Ep) production in the fetus, this function is assumed by kidneys in the adult. The mechanisms underlying the liver to kidney switch of Ep formation are not understood. We studied the natural progression of this transition in sheep by measuring Ep production in response to anemia in normal and bilaterally nephrectomized fetal and newborn sheep beginning at about 80 d gestation (normal gestation: 140 d). Removal of both kidneys before induction of anemia did not affect Ep formation up to about 120 d of gestation. A significant reduction (29%, P < 0.02) in Ep synthesis was first noted at about 130 d of gestation (initiation of switch). This level of nephrectomy-induced reduction of Ep formation persisted until about 15 d after birth. Thereafter, bilateral nephrectomy caused further significant decreases (P < 0.05) in Ep production, gradually resulting in near total absence of Ep production at about day 40 postpartum (completion of switch). Chronic administration of testosterone (12 mg/wk) or estradiole benzoate (1.5 mg/d, 5 d/wk) to the fetus/newborn beginning at 85-90 d of gestation enhanced or suppressed erythropoiesis, respectively, but failed to affect the time at which the liver to kidney switch was initiated and/or completed. By contrast, a significant delay (P < 0.001) in the onset, but not completion of the switch occurred in animals that were either thyroidectomized or rendered chronically anemic beginning in the second third of the gestation period. Administration of thyroxin (1.2 mg/d, 5 d/wk) to thyroidectomized fetus/newborns not only prevented the delay in the initiation of the switch, but also accelerated the rate at which the switch was completed. These results demonstrate that in sheep (a) the liver to kidney switch of Ep production is initiated in utero during the last third of the gestation period, but is completed after birth, (b) this transition occurs gradually; the assumption of Ep

  6. 21 CFR 862.1260 - Estradiol test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 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 §...

  7. [Systen--transdermal estradiol for substitution following surgical menopause].

    PubMed

    Rachev, E; Karag'ozov, I

    1995-01-01

    The authors investigate the clinical effect of transdermal system delivering 17 beta-estradiol for treatment of 23 patients after bilateral ovariectomy for benign genital tumors. During four to six months treatment Kuppermann index falls and karyopyknotic and maturation indices rise significantly. The side effects are extremely rare. The authors recommend the widely use of Systen for replacement therapy in surgically induced menopause.

  8. Fate of glucuronide conjugated estradiol in the environment

    USDA-ARS?s Scientific Manuscript database

    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...

  9. 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 § 862...

  10. Fate of estradiol and testosterone in anaerobic lagoon digestors

    USDA-ARS?s Scientific Manuscript database

    Laboratory-scale lagoon digestors were constructed, and the fate of 14C-labelled 17ß-estradiol (E2) and testosterone (Test) were monitored for 42 d anaerobically under biological and sterile conditions. Hormone levels decreased in the liquid layer and increased in the sludge with time. At 42 d, 16-2...

  11. 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 § 862...

  12. 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 § 862...

  13. 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 § 862...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  15. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ANIMAL DRUGS § 522.2478 Trenbolone acetate and estradiol benzoate. (a) Specifications. Each implant dose...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone acetate... feed efficiency. (C) Limitations. Implant subcutaneously in ear only. Safety and effectiveness have not...

  16. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ANIMAL DRUGS § 522.2478 Trenbolone acetate and estradiol benzoate. (a) Specifications. Each implant dose...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone acetate... feed efficiency. (C) Limitations. Implant subcutaneously in ear only. Safety and effectiveness have not...

  17. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ANIMAL DRUGS § 522.2478 Trenbolone acetate and estradiol benzoate. (a) Specifications. Each implant dose...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone acetate... feed efficiency. (C) Limitations. Implant subcutaneously in ear only. Safety and effectiveness have not...

  18. Specificity Determinants of CYP1B1 Estradiol Hydroxylation

    PubMed Central

    Nishida, Clinton R.; Everett, Steven

    2013-01-01

    Cytochrome P450 (P450)-catalyzed oxidation of the aromatic ring of estradiol can result in 2- or 4-hydroxylation. Which of these products is formed is biologically important, as the 4-hydroxylated metabolite is carcinogenic, where