Dual roles for macrophages in ovarian cycle-associated development and remodelling of the mammary gland epithelium.
Each ovarian cycle, the mammary gland epithelium rotates through a sequence of hormonally regulated cell proliferation, differentiation and apoptosis. These studies investigate the role of macrophages in this cellular turnover. Macrophage populations and their spatial distribution were found to fluctuate across the cycle. The number of macrophages was highest at diestrus, and the greatest number of macrophages in direct contact with epithelial cells occurred at proestrus. The physiological necessity of macrophages in mammary gland morphogenesis during the estrous cycle was demonstrated in Cd11b-Dtr transgenic mice. Ovariectomised mice were treated with estradiol and progesterone to stimulate alveolar development, and with the progesterone receptor antagonist mifepristone to induce regression of the newly formed alveolar buds. Macrophage depletion during alveolar development resulted in a reduction in both ductal epithelial cell proliferation and the number of alveolar buds. Macrophage depletion during alveolar regression resulted in an increased number of branch points and an accumulation of TUNEL-positive cells. These studies show that macrophages have two roles in the cellular turnover of epithelial cells in the cycling mammary gland; following ovulation, they promote the development of alveolar buds in preparation for possible pregnancy, and they remodel the tissue back to its basic architecture in preparation for a new estrous cycle.
The Robinson Institute, Research Centre for Reproductive Health, and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide 5005, Australia.
Angela C L
AC
Chua
Leigh J
LJ
Hodson
Lachlan M
LM
Moldenhauer
Sarah A
SA
Robertson
Wendy V
WV
Ingman
D000818:Animals; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000097:blood / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006727:Hormone Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008264:Macrophages / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000097:blood / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors
D004967:Estrogens; D006727:Hormone Antagonists; D011372:Progestins; D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol