Submitted to: Tissue and Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 15, 2002
Publication Date: March 15, 2002
Citation: CAPUCO, A.V., ELLIS, S.E., GARRETT, W.M., AKERS, R.M. POSTNATAL MAMMARY DUCTAL GROWTH: THREE-DIMENSIONAL IMAGING OF CELL PROLIFERATION, EFFECTS OF ESTROGEN TREATMENT AND EXPRESSION OF STEROID RECEPTORS IN PREPUBERTAL CALVES. TISSUE AND CELL. vol. 34(3), pp. 9-20, 2002.
Interpretive Summary: Growth of the bovine mammary gland was evaluated in 3-month old calves. At that age, the mammary epithelium proliferates to produce the ductular network that provides the framework upon which the secretory elements of the mammary gland develop during pregnancy. We generated three dimensional reconstructions of the proliferating ducts from serial histological sections of the tissue. These reconstructions showed that the growing ducts branched extensively as they elongated and that cell proliferation was distributed throughout the network of nascent ducts. However, the cells that replicated were not those that sensed the presence of estrogen, i.e. contained estrogen receptors. This suggests that a locally produced molecule is likely involved in mediating the stimulation of mammary growth by estrogens. Many of the features of mammary growth in the bovine differ significantly from that in mice, which are often used as a model to study mammary growth and development. Rather, many aspects of growth in the bovine mammary gland are similar to that in the human breast.
The tissue architecture of the bovine mammary gland closely resembles that of the human breast. Consequently, the bovine mammary gland may provide insights into mammary development that are not easily obtained using mouse models. The nature of mammary growth in control and estrogen-treated calves was investigated. Seventy-two hours after the initiation of hormone treatment, calves were injected intravenously with bromodeoxyuridine (BrdU and killed 1 to 2 hours later. BrdU labeled cells were localized in the epithelium of mammary ducts and in stromal cells. Proliferating epithelial cells were present in ducts that contained a lumen and in distal regions where the ductal outgrowths were solid chords of epithelium. Cells along the basal portion of the epithelium also incorporated BrdU, expressed cytokeratin 19, and because they did not express alpha-smooth muscle actin, did not appear to be myoepithelial. Mammary cell proliferation was increased by estrogen treatment. Estrogen (ER) and progesterone (PR) receptors were co-localized in the nuclei of ductal epithelial cells. However, basal cells and epithelial cells that were located in the central region of epithelial chords and those that lined the lumen of patent ducts were estrogen and progesterone receptor negative, as were stromal cells. The presence of estrogen receptor in bovine mammary epithelial cells but not stromal cells is analogous to patterns in the human breast but contrasts with its reported localization in murine mammary gland. Data suggest that proliferation in response to estrogen treatment was initiated within ER-positive epithelial cells of the developing mammary gland and the signal was propagated in paracrine fashion to stromal elements and surrounding ER-negative epithelial cells.