Hepatic gene expression following consumption of soy protein isolate in female Sprague-Dawley rats differs from that produced by 17{beta}-estradiol treatment.

Although soy foods have been recognized as an excellent source of protein, there have been recent concerns regarding potential adverse effects of isoflavone phytochemicals found in soy products, which are known to bind and activate estrogen receptors. Here, we used global hepatic gene expression profiles in ovariectomized female Sprague-Dawley rats treated with 17beta-estradiol (E(2)) or fed with soy protein isolate (SPI) as a means of estimating potential estrogenicity of SPI. Female Sprague-Dawley rats were fed AIN-93G diets containing casein (CAS) or SPI starting at postnatal day (PND) 30. Rats were ovariectomized on PND 50 and infused with E(2) or vehicle in osmotic pumps for 14 d. Microarray analysis was performed on liver using Affymetrix GeneChip Rat 230 2.0. Serum E(2) levels were within normal ranges for the rat and SPI feeding did not increase uterine wet weight in the absence or presence of E(2). SPI feeding altered (P<0.05, >or=+/-1.5-fold) the expression of 82 genes, while E(2) treatment altered 892 genes. Moreover, only 4% of E(2)-affected genes were also modulated by SPI, including some whose expression was reversed by SPI feeding. The interaction between E(2) and SPI uniquely modulated the expression profile of 225 genes including the reduction of those involved in fatty acid biosynthesis or glucocorticoid signaling and an induction of those involved in cholesterol metabolism. The different hepatic gene signatures produced by SPI feeding compared with E(2) and the lack of increase in uterine wet weight in rats fed with SPI suggest that SPI is not estrogenic in these tissues.