title: Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats.
abstract: 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.
authors.affiliation: Institute for Biological Research, Siniša Stanković, University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia. Electronic address: brankasj@ibiss.bg.ac.rs.
authors.forename: Branka
authors.initials: B
authors.lastname: Šošić-Jurjević
authors.affiliation: Institute for Biological Research, Siniša Stanković, University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia.
authors.forename: Branko
authors.initials: B
authors.lastname: Filipović
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
authors.forename: Eva Katrin
authors.initials: EK
authors.lastname: Wirth
authors.affiliation: Institute for Biological Research, Siniša Stanković, University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Živanović
authors.affiliation: Department of Chemistry, Faculty of Science and Mathematics, University of Niš, Višegradska 33, 18000 Niš, Serbia.
authors.forename: Niko
authors.initials: N
authors.lastname: Radulović
authors.affiliation: Institute for Science Application in Agriculture, University of Belgrade, Despot Stefan Blvd. 68b, 11000 Belgrade, Serbia.
authors.forename: Snežana
authors.initials: S
authors.lastname: Janković
authors.affiliation: Institute for Biological Research, Siniša Stanković, University of Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia.
authors.forename: Verica
authors.initials: V
authors.lastname: Milošević
authors.affiliation: Institut für Experimentelle Endokrinologie, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
mesh_terms: D000367:Age Factors; D000818:Animals; D019833:Genistein / Q000633:toxicity; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology*; D007279:Injections, Subcutaneous; D007529:Isoflavones / Q000633:toxicity*; D008297:Male; D009919:Orchiectomy; D051381:Rats; D017208:Rats, Wistar; D030262:Soybean Proteins / Q000633:toxicity*; D013963:Thyroid Hormones / Q000378:metabolism*
chemical_list: D007529:Isoflavones; D030262:Soybean Proteins; D013963:Thyroid Hormones; C004742:daidzein; D019833:Genistein
keywords: Daidzein; Genistein; Isoflavones; Middle age; Rat; Thyroid homeostasis