Soy protein isolate increases hepatic thyroid hormone receptor content and inhibits its binding to target genes in rats

Our previous studies showed that intake of 20% alcohol-washed soy protein isolate (SPI) significantly increased hepatic thyroid hormone receptor (TR) [beta]1 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 TR[beta]1 content and the binding of TR to thyroid hormone response element (I-RE) in rats. Sprague-Dawley rats (28 d old) were fed diets containing casein (20%) with or without isofiavone supplementation (50 mg/kg diet) or alcohol-washed SPI (5, 10, or 20%) for 90 d. The hepatic TR/31 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 TR/31 content in both male and female rats compared with a casein-based control diet. The increase in TR[beta]1 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 TR[beta]1 protein content and inhibits the binding of TR to target genes. Modulation of hepatic TR[beta]1, 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. J. Nutr. 135: 1631-1635, 2005. KEY WORDS: * rat * soy protein * isoflavones * thyroid hormone receptor * binding ability