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Submitted on March 13, 2002
Accepted on June 4, 2002
1 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030-3498. Division of Molecular Biology of the Cell I, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
* To whom correspondence should be addressed. E-mail: jrosen{at}bcm.tmc.edu.
To study the role of GR at different stages of mammary gland development, mammary anlage were rescued from GR --/--mice by transplantation into the cleared fat pad of wild type mice. In virgin mice GR --/--outgrowths displayed abnormal ductal morphogenesis characterized by distended lumena, multiple layers of luminal epithelial cells in some regions along the ducts and increased periductal stroma. In contrast, the loss of GR did not result in overt phenotypic changes in mammary gland development during pregnancy, lactation and involution. Surprisingly, despite the known synergism between glucocorticoids and PRL in the regulation of milk protein gene expression, WAP and ß-casein mRNA levels were unaffected in GR --/--transplants as compared with wild type transplants. That MR might compensate for the loss of GR was suggested by the detection of MR in the mammary gland at day one of lactation. This hypothesis was tested using explant cultures derived from the GR --/-- transplants in which the mineralocorticoid fludrocortisone was able to synergistically induce ß-casein gene expression in the presence of PRL and insulin. These studies suggest that MR may compensate for the absence of GR at some, but not at all stages of mammary gland development.
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