TY  - JOUR
AU  - Šošić-Jurjević, Branka 
AU  - Lütjohann, Dieter
AU  - Renko, Kostja
AU  - Filipović, Branko
AU  - Radulović, Niko
AU  - Ajdžanović, Vladimir
AU  - Trifunović, Svetlana
AU  - Nestorović, Nataša
AU  - Živanović, Jasmina
AU  - Manojlović-Stojanoski, Milica
AU  - Kӧhrle, Josef
AU  - Milošević, Verica
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0960076018307507
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3305
AB  - We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.
T2  - The Journal of Steroid Biochemistry and Molecular Miology
T1  - The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.
VL  - 190
DO  - 10.1016/j.jsbmb.2019.03.009
SP  - 1
EP  - 10
ER  - 

@article{
author = "Šošić-Jurjević, Branka  and Lütjohann, Dieter and Renko, Kostja and Filipović, Branko and Radulović, Niko and Ajdžanović, Vladimir and Trifunović, Svetlana and Nestorović, Nataša and Živanović, Jasmina and Manojlović-Stojanoski, Milica and Kӧhrle, Josef and Milošević, Verica",
year = "2019",
abstract = "We examined whether isoflavones interfere with thyroid homeostasis, increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in middle-aged (MA) male rats. Thirteen-month-old Wistar rats were injected subcutaneously with 35 mg/kg b.w./day of genistein, daidzein or vehicle (controls) for four weeks. Hepatic Dio1 gene expression was up-regulated by 70% (p < 0.001 for both) and Dio1 enzyme activity increased by 64% after genistein (p < 0.001) and 73% after daidzein treatment (p < 0.0001). Hepatic T3 was 75% higher (p < 0.05 for both), while T4 increased only after genistein treatment. Serum T4 concentrations were 31% lower in genistein- and 49% lower in dadzein-treated rats (p < 0.001 for both) compared with controls. Hepatic Cyp7a1 gene expression was up-regulated by 40% after genistein and 32% after daidzein treatment (p < 0.05 for both), in agreement with a 7α-hydroxycholesterol increase of 50% (p < 0.01) and 88% (p < 0.001), respectively. Serum 24- and 27-hydroxycholesterol were 30% lower (p < 0.05 for both), while only 24-hydroxycholesterol was decreased in the liver by 45% after genistein (p < 0.05) and 39% (p < 0.01) after dadzein treatment. Serum concentration of the cholesterol precursor desmosterol was 32% (p < 0.05) lower only after dadzein treatment alone, while both isoflavones elevated this parameter in the liver by 45% (p < 0.01). In conclusion, isoflavones increased T3 availability in the liver of MA males, despite decreasing serum T4. Hepatic increase of T3 possibly contributes to activation of the neutral pathway of cholesterol degradation into bile acids in the liver. While isoflavones obviously have the potential to trigger multiple mechanisms involved in cholesterol metabolism and oxysterol production, they failed to induce any hypocholesterolemic effect.",
journal = "The Journal of Steroid Biochemistry and Molecular Miology",
title = "The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.",
volume = "190",
doi = "10.1016/j.jsbmb.2019.03.009",
pages = "1-10"
}

Šošić-Jurjević, B., Lütjohann, D., Renko, K., Filipović, B., Radulović, N., Ajdžanović, V., Trifunović, S., Nestorović, N., Živanović, J., Manojlović-Stojanoski, M., Kӧhrle, J.,& Milošević, V.. (2019). The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.. in The Journal of Steroid Biochemistry and Molecular Miology, 190, 1-10.
https://doi.org/10.1016/j.jsbmb.2019.03.009

Šošić-Jurjević B, Lütjohann D, Renko K, Filipović B, Radulović N, Ajdžanović V, Trifunović S, Nestorović N, Živanović J, Manojlović-Stojanoski M, Kӧhrle J, Milošević V. The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats.. in The Journal of Steroid Biochemistry and Molecular Miology. 2019;190:1-10.
doi:10.1016/j.jsbmb.2019.03.009 .

Šošić-Jurjević, Branka , Lütjohann, Dieter, Renko, Kostja, Filipović, Branko, Radulović, Niko, Ajdžanović, Vladimir, Trifunović, Svetlana, Nestorović, Nataša, Živanović, Jasmina, Manojlović-Stojanoski, Milica, Kӧhrle, Josef, Milošević, Verica, "The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats." in The Journal of Steroid Biochemistry and Molecular Miology, 190 (2019):1-10,
https://doi.org/10.1016/j.jsbmb.2019.03.009 . .

TY  - JOUR
AU  - Šošić-Jurjević, Branka
AU  - Filipović, Branko
AU  - Wirth, Eva Katrin
AU  - Živanović, Jasmina
AU  - Radulović, Niko
AU  - Janković, Snežana
AU  - Milošević, Verica
AU  - Köhrle, Josef
PY  - 2014
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6134
AB  - We previously reported that genistein (G) and daidzein (D) administered subcutaneously (10 mg/kg) induce changes in the angio-follicular units of the thyroid gland, reduce concentration of total thyroid hormones (TH) and increase thyrotropin (TSH) in serum of orchidectomized middle-aged (16-month-old) rats. To further investigate these effects, we now examined expression levels of the thyroglobulin (Tg), thyroperoxidase (Tpo), vascular endothelial growth factor A (Vegfa) and deiodinase type 1 (Dio 1) genes in the thyroid; in the pituitary, genes involved in TH feedback control (Tsh beta, Dio 1, Dio 2, Trh receptor); and in the liver and kidney, expression of T-3-activated genes Dio 1 and Spot 14, as well as transthyretin (Ttr), by quantitative real-time PCR. We also analyzed TPO-immunopositivity and immunofluorescence of T-4 bound to Tg, determined thyroid T-4 levels and measured deiodinase enzyme activities in examined organs. Decreased expression of Tg and Tpo genes (p < 0.05) correlated with immunohistochemical staining results, and together with decreased serum total T-4 levels, indicates decreased Tg and TH synthesis following treatments with both isoflavones. However, expression of Spot 14 (p < 0.05) gene in liver and kidney was up-regulated, and liver Dio 1 expression and activity (p < 0.05) increased. At the level of pituitary, no significant change in gene expression levels, or Dio 1 and 2 enzyme activities was observed. In conclusion, both G and D impaired Tg and TH synthesis, but at the same time increased tissue availability of TH in peripheral tissues of Orx middle-aged rats.
PB  - Elsevier Inc
T2  - Toxicology and Applied Pharmacology
T1  - Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats
IS  - 2
VL  - 278
DO  - 10.1016/j.taap.2014.04.018
SP  - 124
EP  - 134
ER  - 

@article{
author = "Šošić-Jurjević, Branka and Filipović, Branko and Wirth, Eva Katrin and Živanović, Jasmina and Radulović, Niko and Janković, Snežana and Milošević, Verica and Köhrle, Josef",
year = "2014",
abstract = "We previously reported that genistein (G) and daidzein (D) administered subcutaneously (10 mg/kg) induce changes in the angio-follicular units of the thyroid gland, reduce concentration of total thyroid hormones (TH) and increase thyrotropin (TSH) in serum of orchidectomized middle-aged (16-month-old) rats. To further investigate these effects, we now examined expression levels of the thyroglobulin (Tg), thyroperoxidase (Tpo), vascular endothelial growth factor A (Vegfa) and deiodinase type 1 (Dio 1) genes in the thyroid; in the pituitary, genes involved in TH feedback control (Tsh beta, Dio 1, Dio 2, Trh receptor); and in the liver and kidney, expression of T-3-activated genes Dio 1 and Spot 14, as well as transthyretin (Ttr), by quantitative real-time PCR. We also analyzed TPO-immunopositivity and immunofluorescence of T-4 bound to Tg, determined thyroid T-4 levels and measured deiodinase enzyme activities in examined organs. Decreased expression of Tg and Tpo genes (p < 0.05) correlated with immunohistochemical staining results, and together with decreased serum total T-4 levels, indicates decreased Tg and TH synthesis following treatments with both isoflavones. However, expression of Spot 14 (p < 0.05) gene in liver and kidney was up-regulated, and liver Dio 1 expression and activity (p < 0.05) increased. At the level of pituitary, no significant change in gene expression levels, or Dio 1 and 2 enzyme activities was observed. In conclusion, both G and D impaired Tg and TH synthesis, but at the same time increased tissue availability of TH in peripheral tissues of Orx middle-aged rats.",
publisher = "Elsevier Inc",
journal = "Toxicology and Applied Pharmacology",
title = "Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats",
number = "2",
volume = "278",
doi = "10.1016/j.taap.2014.04.018",
pages = "124-134"
}

Šošić-Jurjević, B., Filipović, B., Wirth, E. K., Živanović, J., Radulović, N., Janković, S., Milošević, V.,& Köhrle, J.. (2014). Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats. in Toxicology and Applied Pharmacology
Elsevier Inc., 278(2), 124-134.
https://doi.org/10.1016/j.taap.2014.04.018

Šošić-Jurjević B, Filipović B, Wirth EK, Živanović J, Radulović N, Janković S, Milošević V, Köhrle J. Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats. in Toxicology and Applied Pharmacology. 2014;278(2):124-134.
doi:10.1016/j.taap.2014.04.018 .

Šošić-Jurjević, Branka, Filipović, Branko, Wirth, Eva Katrin, Živanović, Jasmina, Radulović, Niko, Janković, Snežana, Milošević, Verica, Köhrle, Josef, "Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats" in Toxicology and Applied Pharmacology, 278, no. 2 (2014):124-134,
https://doi.org/10.1016/j.taap.2014.04.018 . .