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  - Lütjohann, Dieter
AU  - Jarić, Ivana
AU  - Miler, Marko
AU  - Vojnović-Milutinović, Danijela
AU  - Filipović, Branko
AU  - Ajdžanović, Vladimir
AU  - Renko, Kostja
AU  - Wirth, Eva Katrin
AU  - Janković, Snežana
AU  - Kӧhrle, Josef
AU  - Milošević, Verica
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S053155651630585X
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2722
AB  - Soy-food and its isoflavones, genistein (G) and daidzein (D), were reported to exert mild cholesterol-lowering effect, but the underlying mechanism is still unclear. In this research, first we studied age-related alterations in hepatic cholesterol metabolism of acyclic middle-aged (MA) female rats. Then we tested if purified isoflavones may prevent or reverse these changes, and whether putative changes in hepatic thyroid hormone availability may be associated with this effect. Serum and hepatic total cholesterol (TChol), bile acid and cholesterol precursors, as well as serum TSH and T4 concentrations, hepatic deiodinase (Dio) 1 enzyme activity and MCT8 protein expression were determined by comparing data obtained for MA with young adult (YA) intact (IC) females. Effects of subcutaneously administered G or D (35 mg/kg) to MA rats were evaluated versus vehicle-treated MA females. MA IC females were characterized by: higher (p < 0.05) serum TChol, lower (p < 0.05) hepatic TChol and its biosynthetic precursors, lower (p < 0.05) hepatic 7α-hydroxycholesterol but elevated (p < 0.05) 27- and 24-hydroxycholesterol in comparison to YA IC. Both isoflavone treatments decreased (p < 0.05) hepatic 27-hydroxycholesterol, G being more effective than D, without affecting any other parameter of Chol metabolism. Only G elevated hepatic Dio1 activity (p < 0.05). In conclusion, age-related hypercholesteremia was associated with lower hepatic Chol synthesis and shift from main neutral (lower 7α-hydroxycholesterol) to alternative acidic pathway (higher 27-hydroxycholesterol) of Chol degradation to bile acid. Both isoflavones lowered hepatic 27-hydroxycholesterol, which may be considered beneficial. Only G treatment increased hepatic Dio1 activity, thus indicating local increase in thyroid hormones, obviously insufficient to induce prominent cholesterol-lowering effect.
T2  - Experimental Gerontology
T1  - Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats
VL  - 92
DO  - 10.1016/j.exger.2017.03.016
SP  - 74
EP  - 81
ER  - 

@article{
author = "Šošić-Jurjević, Branka and Lütjohann, Dieter and Jarić, Ivana and Miler, Marko and Vojnović-Milutinović, Danijela and Filipović, Branko and Ajdžanović, Vladimir and Renko, Kostja and Wirth, Eva Katrin and Janković, Snežana and Kӧhrle, Josef and Milošević, Verica",
year = "2017",
abstract = "Soy-food and its isoflavones, genistein (G) and daidzein (D), were reported to exert mild cholesterol-lowering effect, but the underlying mechanism is still unclear. In this research, first we studied age-related alterations in hepatic cholesterol metabolism of acyclic middle-aged (MA) female rats. Then we tested if purified isoflavones may prevent or reverse these changes, and whether putative changes in hepatic thyroid hormone availability may be associated with this effect. Serum and hepatic total cholesterol (TChol), bile acid and cholesterol precursors, as well as serum TSH and T4 concentrations, hepatic deiodinase (Dio) 1 enzyme activity and MCT8 protein expression were determined by comparing data obtained for MA with young adult (YA) intact (IC) females. Effects of subcutaneously administered G or D (35 mg/kg) to MA rats were evaluated versus vehicle-treated MA females. MA IC females were characterized by: higher (p < 0.05) serum TChol, lower (p < 0.05) hepatic TChol and its biosynthetic precursors, lower (p < 0.05) hepatic 7α-hydroxycholesterol but elevated (p < 0.05) 27- and 24-hydroxycholesterol in comparison to YA IC. Both isoflavone treatments decreased (p < 0.05) hepatic 27-hydroxycholesterol, G being more effective than D, without affecting any other parameter of Chol metabolism. Only G elevated hepatic Dio1 activity (p < 0.05). In conclusion, age-related hypercholesteremia was associated with lower hepatic Chol synthesis and shift from main neutral (lower 7α-hydroxycholesterol) to alternative acidic pathway (higher 27-hydroxycholesterol) of Chol degradation to bile acid. Both isoflavones lowered hepatic 27-hydroxycholesterol, which may be considered beneficial. Only G treatment increased hepatic Dio1 activity, thus indicating local increase in thyroid hormones, obviously insufficient to induce prominent cholesterol-lowering effect.",
journal = "Experimental Gerontology",
title = "Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats",
volume = "92",
doi = "10.1016/j.exger.2017.03.016",
pages = "74-81"
}

Šošić-Jurjević, B., Lütjohann, D., Jarić, I., Miler, M., Vojnović-Milutinović, D., Filipović, B., Ajdžanović, V., Renko, K., Wirth, E. K., Janković, S., Kӧhrle, J.,& Milošević, V.. (2017). Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats. in Experimental Gerontology, 92, 74-81.
https://doi.org/10.1016/j.exger.2017.03.016

Šošić-Jurjević B, Lütjohann D, Jarić I, Miler M, Vojnović-Milutinović D, Filipović B, Ajdžanović V, Renko K, Wirth EK, Janković S, Kӧhrle J, Milošević V. Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats. in Experimental Gerontology. 2017;92:74-81.
doi:10.1016/j.exger.2017.03.016 .

Šošić-Jurjević, Branka, Lütjohann, Dieter, Jarić, Ivana, Miler, Marko, Vojnović-Milutinović, Danijela, Filipović, Branko, Ajdžanović, Vladimir, Renko, Kostja, Wirth, Eva Katrin, Janković, Snežana, Kӧhrle, Josef, Milošević, Verica, "Effects of age and soybean isoflavones on hepatic cholesterol metabolism and thyroid hormone availability in acyclic female rats" in Experimental Gerontology, 92 (2017):74-81,
https://doi.org/10.1016/j.exger.2017.03.016 . .

TY  - JOUR
AU  - Šošić-Jurjević, Branka 
AU  - Filipović, Branko
AU  - Renko, Kostja
AU  - Ajdžanović, Vladimir
AU  - Manojlović-Stojanoski, Milica
AU  - Milošević, Verica
AU  - Koehrle, Josef
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1091
AB  - Endogenous androgens are involved in regulation of thyroid function and metabolism of thyroid hormones. As serum testosterone level progressively declines with age, this regulation may change. We tested how androgen deprivation, achieved by orchidectomy, affects thyroid homeostasis in middle-aged rats. Fifteen-month-old Wistar rats were orchidectomized (Orx) or sham-operated under ketamine anesthesia (15 mg/kg body weight). Five weeks after the surgery, animals were decapitated. Thyroids were used for histomorphometric and ultrastructural examinations and together with livers and pituitaries for real-time quantitative PCR and deiodinase (DIO) activity measurements. Serum testosterone, TSH, L-thyroxine (T-4), and cholesterol (Chol) levels were determined. As expected, middle-aged control rats had lower (P<0.05) testosterone and T-4 compared with 3-month-old males. In the Orx middle-aged group, we detected diminished serum testosterone (P<0.05), no change in TSH and T-4 levels, and higher Chol level (P<0.05), in comparison with age-matched controls. Histomorphometric analysis of thyroid tissue revealed decreased relative volume densities of follicles and colloid (P<0.05). Relevant gene expressions and DIO1 enzyme activity were not changed in the thyroids of Orx rats. Liver Dio1 gene expression and DIO1 activity were decreased (P<0.05) in comparison with the control values. Pituitary levels of TSH beta, Dio1, and Dio2 mRNAs did not change, while DIO2 activity decreased (P<0.05). In conclusion, orchidectomy of middle-aged rats affected thyroid structure with no effect on serum T-4 and TSH. However, decreased liver DIO1 and pituitary DIO2 enzyme activities indicate compensatory-adaptive changes in local T-3 production. Journal of Endocrinology (2012) 215, 247-256
PB  - Society for Endocrinology
T2  - Journal of Endocrinology
T1  - Orchidectomy of middle-aged rats decreases liver deiodinase 1 and pituitary deiodinase 2 activity
IS  - 2
VL  - 215
DO  - 10.1530/JOE-12-0336
SP  - 325
EP  - 256
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1091
ER  - 

@article{
author = "Šošić-Jurjević, Branka  and Filipović, Branko and Renko, Kostja and Ajdžanović, Vladimir and Manojlović-Stojanoski, Milica and Milošević, Verica and Koehrle, Josef",
year = "2012",
abstract = "Endogenous androgens are involved in regulation of thyroid function and metabolism of thyroid hormones. As serum testosterone level progressively declines with age, this regulation may change. We tested how androgen deprivation, achieved by orchidectomy, affects thyroid homeostasis in middle-aged rats. Fifteen-month-old Wistar rats were orchidectomized (Orx) or sham-operated under ketamine anesthesia (15 mg/kg body weight). Five weeks after the surgery, animals were decapitated. Thyroids were used for histomorphometric and ultrastructural examinations and together with livers and pituitaries for real-time quantitative PCR and deiodinase (DIO) activity measurements. Serum testosterone, TSH, L-thyroxine (T-4), and cholesterol (Chol) levels were determined. As expected, middle-aged control rats had lower (P<0.05) testosterone and T-4 compared with 3-month-old males. In the Orx middle-aged group, we detected diminished serum testosterone (P<0.05), no change in TSH and T-4 levels, and higher Chol level (P<0.05), in comparison with age-matched controls. Histomorphometric analysis of thyroid tissue revealed decreased relative volume densities of follicles and colloid (P<0.05). Relevant gene expressions and DIO1 enzyme activity were not changed in the thyroids of Orx rats. Liver Dio1 gene expression and DIO1 activity were decreased (P<0.05) in comparison with the control values. Pituitary levels of TSH beta, Dio1, and Dio2 mRNAs did not change, while DIO2 activity decreased (P<0.05). In conclusion, orchidectomy of middle-aged rats affected thyroid structure with no effect on serum T-4 and TSH. However, decreased liver DIO1 and pituitary DIO2 enzyme activities indicate compensatory-adaptive changes in local T-3 production. Journal of Endocrinology (2012) 215, 247-256",
publisher = "Society for Endocrinology",
journal = "Journal of Endocrinology",
title = "Orchidectomy of middle-aged rats decreases liver deiodinase 1 and pituitary deiodinase 2 activity",
number = "2",
volume = "215",
doi = "10.1530/JOE-12-0336",
pages = "325-256",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1091"
}

Šošić-Jurjević, B., Filipović, B., Renko, K., Ajdžanović, V., Manojlović-Stojanoski, M., Milošević, V.,& Koehrle, J.. (2012). Orchidectomy of middle-aged rats decreases liver deiodinase 1 and pituitary deiodinase 2 activity. in Journal of Endocrinology
Society for Endocrinology., 215(2), 325-256.
https://doi.org/10.1530/JOE-12-0336
https://hdl.handle.net/21.15107/rcub_ibiss_1091

Šošić-Jurjević B, Filipović B, Renko K, Ajdžanović V, Manojlović-Stojanoski M, Milošević V, Koehrle J. Orchidectomy of middle-aged rats decreases liver deiodinase 1 and pituitary deiodinase 2 activity. in Journal of Endocrinology. 2012;215(2):325-256.
doi:10.1530/JOE-12-0336
https://hdl.handle.net/21.15107/rcub_ibiss_1091 .

Šošić-Jurjević, Branka , Filipović, Branko, Renko, Kostja, Ajdžanović, Vladimir, Manojlović-Stojanoski, Milica, Milošević, Verica, Koehrle, Josef, "Orchidectomy of middle-aged rats decreases liver deiodinase 1 and pituitary deiodinase 2 activity" in Journal of Endocrinology, 215, no. 2 (2012):325-256,
https://doi.org/10.1530/JOE-12-0336 .,
https://hdl.handle.net/21.15107/rcub_ibiss_1091 .