|Ronis, Martin -|
|Shankar, Kartik -|
|Gomez-Acevedo, Horatio -|
|Hennings, Leah -|
|Singhal, Rohit -|
|Blackburn, Michael -|
Submitted to: Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 10, 2012
Publication Date: December 1, 2012
Citation: Ronis, M.J., Shankar, K., Gomez-Acevedo, H., Hennings, L., Singhal, R., Blackburn, M., Badger, T.M. 2012. Mammary gland morphology and gene expression differ in female rats treated with 17 beta-estradiol or fed soy protein isolate. Endocrinology. 153(12):6021-6032. Interpretive Summary: Soy foods have been suggested to have many positive health benefits, such as improved cholesterol levels, increased insulin sensitivity, improved bone quality, and decreased cancer risk. However, soy foods have also been suggested to have potentially toxic effects on reproductive development and fertility, and to increase the risk of certain hormone-related cancers, such as breast cancer, as a result of their content of so-called "phytoestrogens". Two soy-protein associated plant chemicals, genistein and daidzein, are suspected to act like estrogens. In this study, we directly compared the effects of soy protein with those of the major female hormone 17'-estradiol (E2) in the female rat breast. The data suggest soy protein is not estrogenic in the rat breast and therefore the risk of toxicity from early estrogenic actions of soy protein containing soy infant formulas is likely to be negligible. Moreover, our data is consistent with epidemiological studies of breast cancer incidence in Asian populations, which suggests that eating soy foods reduces rather than increases risk of breast cancer and even reduces the risk of breast cancer re-occurrence in women previously diagnosed and treated for breast cancer.
Technical Abstract: Soy foods have been suggested to have both positive health benefits and potentially adverse effects as a result of their content of phytoestrogens. However, studies on the estrogenicity of soy foods are lacking. Here we directly compared the effects of soy protein isolate (SPI), the protein in soy infant formula, with those of 17 beta-estradiol (E2) on global gene expression profiles and morphology in the female rat mammary gland. Rats were fed AIN-93G diets containing casein (CAS) or SPI beginning on postnatal day (PND)30. Rats were ovariectomized (OVX) on PND50 and treated with 5 micro g/kg/d E2 or vehicle for 14 d. Microarray analysis revealed that E2 treatment altered expression of 780 genes =2-fold (P<0.05), while SPI feeding altered expression of only 53 genes =2-fold. Moreover, the groups had only 10 genes in common to increase =2-fold. The combination of SPI feeding and E2 altered expression of 422 genes and reversed E2 effects on many mRNAs, including those involved in the c-myc signaling pathway, cyclin D1 and Ki67. ER alpha binding to its response element on the Tie-2/Tek and progesterone receptor (pgr) promoters was increased by E2, but not SPI, and this promoter binding was suppressed by the combination of E2 + SPI for the Tie-2/Tek promoter but increased for the pgr promoter (P<0.05). SPI reduced the ratio of epithelial to fat pad area and E2 + SPI reduced both epithelial and fat pad area (P<0.05). These data suggest SPI is not estrogenic in the rat mammary gland even in the absence of endogenous estrogens.