Data from Effects of Pubertal Exposure to Dietary Soy on Estrogen Receptor Activity in the Breast of Cynomolgus Macaques

Abstract

<div>Abstract<p>Endogenous estrogens influence mammary gland development during puberty and breast cancer risk during adulthood. Early-life exposure to dietary or environmental estrogens may alter estrogen-mediated processes. Soy foods contain phytoestrogenic isoflavones (IF), which have mixed estrogen agonist/antagonist properties. Here, we evaluated mammary gland responses over time in pubertal female cynomolgus macaques fed diets containing either casein/lactalbumin (<i>n</i> = 12) or soy protein containing a human-equivalent dose of 120 mg IF/day (<i>n</i> = 17) for approximately 4.5 years spanning menarche. We assessed estrogen receptor (ER) expression and activity, promoter methylation of ERs and their downstream targets, and markers of estrogen metabolism. Expression of ERα and classical ERα response genes <i>(TFF1, PGR</i>, and <i>GREB1</i>) decreased with maturity, independent of diet. A significant inverse correlation was observed between <i>TFF1</i> mRNA and methylation of CpG sites within the <i>TFF1</i> promoter. Soy effects included lower ERβ expression before menarche and lower mRNA for ERα and <i>GREB1</i> after menarche. Expression of GATA-3, an epithelial differentiation marker that regulates ERα-mediated transcription, was elevated before menarche and decreased after menarche in soy-fed animals. Soy did not significantly alter expression of other ER activity markers, estrogen-metabolizing enzymes, or promoter methylation for ERs or ER-regulated genes. Our results demonstrate greater ER expression and activity during the pubertal transition, supporting the idea that this life stage is a critical window for phenotypic modulation by estrogenic compounds. Pubertal soy exposure decreases mammary ERα expression after menarche and exerts subtle effects on receptor activity and mammary gland differentiation. <i>Cancer Prev Res; 9(5); 385–95. ©2016 AACR</i>.</p></div>