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Toxicol Appl Pharmacol. 2014 Jul 15;278(2):124-34. doi: 10.1016/j.taap.2014.04.018. Epub 2014 Apr 29.

Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats.

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Institute for Biological Research, Siniša Stanković, University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia. Electronic address:
Institute for Biological Research, Siniša Stanković, University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia.
Institut für Experimentelle Endokrinologie, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia.
Institute for Science Application in Agriculture, University of Belgrade, Despot Stefan Blvd. 68b, 11000 Belgrade, Serbia.


We previously reported that genistein (G) and daidzein (D) administered subcutaneously (10mg/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 β, Dio 1, Dio 2, Trh receptor); and in the liver and kidney, expression of T3-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 T4 bound to Tg, determined thyroid T4 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 T4 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.


Daidzein; Genistein; Isoflavones; Middle age; Rat; Thyroid homeostasis

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