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Biochemical and Molecular Actions of Nutrients

Soy Protein Isolate Increases Hepatic Thyroid Hormone Receptor Content and Inhibits Its Binding to Target Genes in Rats^1,2,3

Wenxin Huang^*, Carla Wood^*, Mary R. L’Abbé^*, G. Sarwar Gilani^*, Kevin A. Cockell^* and Chao Wu Xiao^*,,4

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

⁴To whom correspondence should be addressed. E-mail: chaowu_xiao{at}hc-sc.gc.ca.

Our previous studies showed that intake of 20% alcohol-washed soy protein isolate (SPI) significantly increased hepatic thyroid hormone receptor (TR) ß1 protein content in rats. However, whether SPI influences the binding ability of TR to its target genes is unknown. The purpose of this study was to examine the effect of increasing amounts of dietary SPI on hepatic TRß1 content and the binding of TR to thyroid hormone response element (TRE) in rats. Sprague-Dawley rats (28 d old) were fed diets containing casein (20%) with or without isoflavone supplementation (50 mg/kg diet) or alcohol-washed SPI (5, 10, or 20%) for 90 d. The hepatic TRß1 protein content was measured by Western blot, and the binding ability of TR to DNA was examined by electrophoretic mobility shift assay. Consumption of the 20% SPI diet increased pancreatic relative weight and decreased spleen relative weight. Intake of SPI markedly elevated TRß1 content in both male and female rats compared with a casein-based control diet. The increase in TRß1 in females was much higher than that in males. Interestingly, the binding abilities of TR to DNA were significantly inhibited by increasing amounts of dietary SPI in female rats. In conclusion, this study shows for the first time that dietary SPI increases hepatic TRß1 protein content and inhibits the binding of TR to target genes. Modulation of hepatic TRß1, a key regulator of gene expression involved in lipid metabolism, by SPI may be a novel mechanism by which soy components lower blood lipid level and exert their hypocholesterolemic actions.

KEY WORDS: • rat • soy protein • isoflavones • thyroid hormone receptor • binding ability

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