Alterations in mammary gland development following neonatal exposure to estradiol, transforming growth factor α, and estrogen receptor antagonist ICI 182,780
✍ Scribed by Leena Hilakivi-Clarke; Elizabeth Cho; Margarita Raygada; Nicholas Kenney
- Book ID
- 101263278
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 441 KB
- Volume
- 170
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
High fetal/early postnatal levels of estrogen increase breast cancer risk, but the mechanisms remain unknown. Growth factors, such as transforming growth factor a (TGFa), may participate as secondary modifiers in this process. We characterized a modulatory role of early postnatal exposure to 17b-estradiol (E 2 ) on the developing mammary gland morphology by treating intact female CD-1 mice with physiological doses of E 2 (2-4 mg), human recombinant TGFa (4 mg), or an estrogen receptor (ER) antagonist ICI 182,780 (20 mg) during postnatal days 1-3. Early postnatal exposure of E 2 stimulated mammary ductal growth by days 25 and 35, but by day 50 this was inhibited. The level of differentiation from terminal end buds (TEBs) to the lobulo-alveolar units (LAUs) also was reduced by day 50. The number of TEBs was increased throughout most of the development in the female mice exposed to E 2 during early life. An exposure to TGFa or ICI 182,780 between postnatal days 1 and 3 stimulated ductal growth, formation of TEBs, and the differentiation of mammary epithelial structures. ICI 182,80 treatment also caused hyperplastic lobular-like structures in 54-day-old females. Thus, neonatal exposure to TGFa and ICI 182,780 induced both similar (increase in TEBs) and different (increase/decrease in lobulo-alveolar differentiation) developmental changes in the mouse mammary gland, when compared with an exposure to E 2 . A unique feature of the postnatal E 2 treatment was that it inhibited ductal migration by days 50-54. Our data suggest than an exposure to E 2 on postnatal days 1-3, possibly combined with secondary epigenetic alterations, leads to various changes within the developing mammary tree. These changes may be potential prerequisites for mammary tumorigenesis.