Dietary Genistein Inactivates Rat Thyroid Peroxidase in Vivo without an Apparent Hypothyroid Effect

doi:10.1006/taap.2000.9019

Toxicology and Applied Pharmacology

Volume 168, Issue 3, 1 November 2000, Pages 244-252

https://doi.org/10.1006/taap.2000.9019 Get rights and content

Abstract

Biological effects of genistein are currently under investigation by the National Toxicology Program because of widespread and increasing soy consumption by humans and evidence for modulation of endocrine function. Rats were exposed to genistein aglycone in soy-free feed fortified at 0, 5, 100, and 500 ppm starting in utero through 20 weeks. Thyroid glands and serum were analyzed for total genistein (aglycone + conjugates) using HPLC with electrospray mass spectrometric detection. Microsomal thyroid peroxidase (TPO) activity was measured spectrophotometrically. The total genistein content in rat serum was as high as 8 μM, and significant dose-dependent increases of genistein in thyroid tissue up to 1 pmol/mg were found in male and female rats. The activity of TPO in male and female rats was found to be reduced by up to 80% in a dose-dependent manner. Male and female rats consuming a standard soy-based rodent diet (NIH 31) had TPO activity approximately 50% lower than rats consuming a soy-free diet and this loss was commensurate with measured serum levels of isoflavones. Suicide inactivation of rat, porcine, and human TPO was observed in vitro at concentrations of genistein aglycone comparable to those measured in rat thyroids. Thyroid hormone levels (T3, T4, TSH) in serum, thyroid weights, and histopathology showed no differences between treated and untreated groups. These findings suggest that, even though substantial amounts of TPO activity are lost concomitant to soy isoflavone consumption by normal rats, the remaining enzymatic activity is sufficient to maintain thyroid homeostasis in the absence of additional perturbations.

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Regular ArticleDietary Genistein Inactivates Rat Thyroid Peroxidase in Vivo without an Apparent Hypothyroid Effect

Abstract

Biochem. Pharmacol.

J. Biol. Chem.

J. Nutr.

Lancet

Triiodothyronine and thyroxine in the serum and thyroid glands of iodine-deficient rats

J. Clin. Invest.

Determination of lignans and isoflavonoids in plasma by isotope dilution GC/MS

Cancer Detect. Prev.

Isoflavones and their conjugates in soy foods: Extraction conditions and analysis by HPLC-mass spectrometry

J. Agric. Food Chem.

The curative action of iodine on soybean goiter and the changes in the distribution of iodoamino acids in the serum and in thyroid gland digests

Arch. Biochem. Biophys.

The Colorado thyroid disease prevalence study

Arch. Intern. Med.

Comparative anatomy and physiology

Development of monoclonal antibodies to the human sodium iodide symporter: Immunohistochemical characterization of this protein in thyroid cells

J. Clin. Endocrinol. Metab.

Mass spectrometric determination of genistein tissue distribution in Sprague Dawley rats from dietary exposure

J. Nutr.

Persistent hypothyroidism in an infant receiving a soy formula: case report and review of the literature

Pediatrics

Studies on the stromal, luminal, and cellular compartments of the thyroid

Endocrinology

Inhibition of thyroid peroxidase by dietary flavonoids

Chem. Res. Toxicol.

Enzymatic conjugation of the soy isoflavones, genistein and daidzein, and analysis in human blood using liquid chromatography and mass spectrometry

Drug. Metab. Disp.

On-line sample preparation using restricted-access media in the LC-ESI/MS analysis of the soy isoflavones, genistein and daidzein, in rat serum

Rapid Commun. Mass Spectrom.

Soy isoflavones exert modest hormonal effects in premenopausal women

J. Clin. Endocrinol. Metab.

Soy isoflavones exert modest hormonal effects of in postmenopausal women

J. Clin. Endocrinol. Metab.

Soy formulas and the effects of isoflavones on the thyroid

N. Z. Med. J.

Quantification of genistein and metabolites in rat blood using LC-ES/MS

J. Agric. Food Chem.

Regular Article
Dietary Genistein Inactivates Rat Thyroid Peroxidase in Vivo without an Apparent Hypothyroid Effect