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The Mineralocorticoid Receptor May Compensate for the Loss of the Glucocorticoid Receptor at Specific Stages of Mammary Gland Development

Department of Molecular and Cellular Biology (M.K.-K., S.S.M., S.L.W., S.S., J.M.R.), Baylor College of Medicine, Houston, Texas 77030-3498; and Division of Molecular Biology of the Cell I (G.S.), German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

Address all correspondence and requests for reprints to: Dr. Jeff Rosen, Department of Molecular and Cellular Biology, M638a Debakey Building, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030-3498. E-mail: jrosen{at}bcm.tmc.edu.

To study the role of glucocorticoid receptor (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 prolactin in the regulation of milk protein gene expression, whey acidic protein and ß-casein mRNA levels were unaffected in GR-/- transplants as compared with wild-type transplants. That mineralocorticoid receptor (MR) might compensate for the loss of GR was suggested by the detection of MR in the mammary gland at d 1 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 prolactin 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.

NURSA Molecule Pages Link:

Nuclear Receptors:   GR  |  MR

Ligands:   Hydrocortisone

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