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Biochemical and Molecular Actions of Nutrients

Dietary Soy Protein Isolate and Isoflavones Modulate Hepatic Thyroid Hormone Receptors in Rats¹

Chao Wu Xiao^*,**,2, Mary R. L’Abbé^*, G. Sarwar Gilani^*, Gerard M. Cooke^,**, Ivan H. Curran and Suzanne A. Papademetriou^*

^* Nutrition Research Division, Toxicology Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada K1A 0L2 and ^** Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada

²To whom correspondence should be addressed. E-mail: chaowu__xiao{at}hc-sc.gc.ca.

Thyroid hormone receptors (TRs) are regulators of many genes involved in cholesterol and lipid metabolism. The purpose of this study was to examine the effect of soy protein isolate (SPI) and isoflavones on hepatic TRs in rats. In Expt. 1, Sprague-Dawley rats were fed diets containing either casein or alcohol-washed SPI with or without isoflavone supplementation (5–1250 mg/kg diet) for 70, 190, and 310 d. The offspring (F1) were fed the same diets as their parents (F0). In Expt. 2, Sprague-Dawley rats were fed diets containing casein or casein plus isoflavones (50–400 mg/kg diet) for 120 d. The mRNA and protein contents of the hepatic TRs were measured by semiquantitative RT-PCR and Western blot, respectively. TR1, TR2, and TRß2 contents were not affected by SPI. However, the content of the 52-kDa TRß1 protein, the major isoform present in the liver, was markedly increased by dietary SPI in both sexes of F0 and F1 compared with casein. The supplemental isoflavones had no effect on TRß1, whereas the high doses of isoflavones (250 and 1250 mg/kg diet) reduced the hepatic TR1 protein content in F1 male rats on d 28. SPI had no effect on total T3 and T4 levels. However, higher dose of supplemental isoflavones markedly increased T4 level in female rats. Overall, this study demonstrates for the first time that SPI upregulates hepatic TRß1 expression, and that isoflavones reduce the hepatic TR1 level in young male rats. The SPI-induced TRß1 may play a role in mediating the hypocholesterolemic and lipid-lowering actions of soy protein.

KEY WORDS: • rats • soy protein isolate • isoflavones • thyroid hormone receptors

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