Location: Arkansas Children's Nutrition CenterTitle: Mammary gland morphology and gene expression signature of prepubertal male and female rats following exposure to exogenous estradiol Author
Submitted to: Toxicologist
Publication Type: Abstract Only
Publication Acceptance Date: 12/4/2012
Publication Date: 3/1/2013
Citation: Ronis, M.J., Miousse, I.R., Vantrease, J., Hennings, L., Shankar, K., Gomez-Acevedo, H., Cleves, M., Badger, T.M. 2013. Mammary gland morphology and gene expression signature of prepubertal male and female rats following exposure to exogenous estradiol [abstract]. Toxicologist. 132(1):Abstract 97, p. 19-20. Interpretive Summary:
Technical Abstract: In order to properly screen environmental chemicals for potential toxic effects such as increased cancer risk and risk of infertility resulting from actions similar to those of female sex steroids such as estrogens, it is essential to understand the effects of treatment with the most important female sex steroid: estradiol. Because the estrogen-dependent gene expression is one of the primary biomarkers of estrogenic action, we have assessed effects of three doses of estradiol (0.1, 1.0, and 10 micrograms/kg of body weight/day) on the structure of the breast and breast gene expression profiles of young male and female rats prior to puberty compared to untreated controls. The breast was more responsive to estradiol treatment in males than in females. There was an increase in the number of breast terminal end buds in males (structures with the largest number of dividing cells with the highest risk of becoming cancerous), and a corresponding increase in the expression of the gene encoding amphiregulin, a protein known to drive the terminal end bud development. In intact females, the highest dose of estradiol tested induced an increase in the expression of genes encoding breast milk components, as well as muscle proteins involved in milk release. Lower doses had limited effects on gene expression. Therefore, the young rat male breast is a very sensitive tissue for use in evaluating estrogenic actions of environmental chemicals using breast structure changes coupled to microarray analysis of gene expression. In contrast, young females were comparatively poorly responsive to estradiol treatment, although many modulated genes were common to both sexes.