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

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


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.

Keywords: Daidzein; Genistein; Isoflavones; Middle age; Rat; Thyroid homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Genistein / toxicity
  • Homeostasis / drug effects*
  • Homeostasis / physiology*
  • Injections, Subcutaneous
  • Isoflavones / toxicity*
  • Male
  • Orchiectomy*
  • Rats
  • Rats, Wistar
  • Soybean Proteins / toxicity*
  • Thyroid Hormones / metabolism*


  • Isoflavones
  • Soybean Proteins
  • Thyroid Hormones
  • daidzein
  • Genistein