The isoflavones genistein and daidzein increase hepatic concentration of thyroid hormones and affect cholesterol metabolism in middle-aged male rats

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 190; pp. 1 - 10
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2019; Elsevier BV
• Subjects: Bile; Bile acids; Cholesterol; Cholesterol metabolism; CYP7A1 gene; Daidzein; DIO1 gene; Enzymatic activity; Gene expression; Genistein; Homeostasis; Isoflavones; Lipid metabolism; Liver; Metabolism; Middle age; Middle-aged rats; Rodents; Thyroid gland; Thyroid homeostasis; Thyroid hormones; Thyroxine; Triiodothyronine; Daidzein; Cholesterol metabolism; Genistein; Liver; Thyroid homeostasis; Middle-aged rats
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2019.03.009

•We examined whether isoflavones increase hepatic thyroid hormone concentrations and affect cholesterol metabolism in rats.•Serum T3 was not affected while hepatic T3 was almost doubled, which supports increased local T3 availability.•Obtained results are compatible with displacement of TH from TTR, major transport protein in rodent blood and human CSF.•Hepatic increase of T3 correlated with up-regulated expression of the Cyp7a1 gene and elevated 7α-hydroxycholesterol.•If also lowered 24-hydroxycholesterol and desmosterol in liver and serum, while the total cholesterol levels remained unchanged.
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.