Lactation Biology Symposium: Mammary gland biology revisited

The mammary gland goes through a coordinated series of developmental states during postnatal life in preparation for lactation. These changes ultimately reflect a changing endocrine environment alongside local alterations in the microenvironment. A longstanding assumption has been that estrogens serve as the first essential component for any of these developmental changes to be realized in the mammary glands. Indeed, estrogens can initiate the onset of allometric growth during puberty, and they subsequently potentiate the effects of other endocrine cues on the mammary epithelium during lobulo-alveolar development throughout gestation. More recent evidence from our laboratory indicates that alternative pathways are equally effective in promoting growth of the mammary glands independent of a primary role for estrogens. One fascinating example is the ability of dietary trans-10,cis-12 conjugated linoleic acid (10,12 CLA) to promote allometric growth of the mammary ducts of ovariectomized mice. In subsequent studies we showed that the specific effects of this dietary fat are independent of estrogenic action, and are mediated through IGF-I receptor signaling. The relevance of these findings is emphasized by the fact that this dietary intervention mimics several aspects of the metabolic syndrome manifest in obese humans. At the same time, additional findings from our laboratory indicate that prolactin and progesterone have synergistic effects on epithelial growth and morphogenesis independent of any role for estrogens, which are partly mediated by changes in the local microenvironment. These data collectively support the notion that while estrogens are clearly mitogenic for the growing and developing mammary glands, they are not necessarily requisite. These findings have potential implications for our understanding of mammary growth in all mammals including livestock, as well as direct relevance to the regulation of mammary cancers.