help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mueller, S. O.
Right arrow Articles by Korach, K. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mueller, S. O.
Right arrow Articles by Korach, K. S.
Endocrinology Vol. 143, No. 6 2357-2365
Copyright © 2002 by The Endocrine Society

REPRODUCTION-DEVELOPMENT

Mammary Gland Development in Adult Mice Requires Epithelial and Stromal Estrogen Receptor {alpha}

Stefan O. Mueller1, James A. Clark, Page H. Myers and Kenneth S. Korach

Laboratory of Reproductive and Developmental Toxicology (S.O.M., K.S.K.) and Comparative Medicine Branch (J.A.C., P.H.M.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709

Address all correspondence and requests for reprints to: Kenneth S. Korach, National Institute on Environmental Health Sciences, MD B3-02, 111 T. W. Alexander Drive, P.O. Box 12233, Research Triangle Park, North Carolina 27709, E-mail: ; or Stefan O. Mueller, Institute of Toxicology, Merck KGaA, 64271 Darmstadt, Germany, E-mail: . stefan.o.mueller{at}merck.de

Complete mammary gland development takes place following puberty and depends on the estrogen receptor (ER){alpha} and the progesterone receptor (PR) and is tightly regulated by the interaction of the mammary epithelium with the stromal compartment. Studies using mammary tissues of immature mice have indicated that stromal but not epithelial ER{alpha} is required for mammary gland growth. This study investigates whether these same tissue growth requirements of neonate tissue are necessary for mammary development and response in adult mice. Mammary epithelial cells were isolated from adult mice with a targeted disruption of the ER{alpha} gene ({alpha}ERKO) or from wild-type counterparts and injected into epithelial-free mammary fat pads of 3-wk-old female {alpha}ERKO or wild-type mice. Ten weeks after cell injection, analysis of mammary gland whole mounts showed that both stromal and epithelial ER{alpha} were required for complete mammary gland development in adult mice. However, when the mice were treated with high doses of estradiol (E2) and progesterone, stromal ER{alpha} was sufficient to generate full mammary gland growth. Surprisingly, ER{alpha}-deficient epithelial cells were able to proliferate and develop into a rudimentary mammary ductal structure in an ER{alpha}-negative stroma, indicating that neither stromal nor epithelial ER{alpha} are required for the mammary rudiment to form in the adult mouse, as confirmed by the phenotype of the {alpha}ERKO mammary gland. Use of thisin vivo model system has demonstrated that neonatal and adult mammary tissues use a different tissue-specific role for ER{alpha} in mammary response. Immunostaining for ER{alpha} and PR in the mammary outgrowths supported the view that both stromal and epithelial ER{alpha}, in cooperation with epithelial PR, govern mammary gland development in adult mice.




This article has been cited by other articles:


Home page
 J EndocrinolHome page
L. M Arendt, L. C Evans, D. E Rugowski, M. J. Garcia-Barchino, H. Rui, and L. A Schuler
Ovarian hormones are not required for PRL-induced mammary tumorigenesis, but estrogen enhances neoplastic processes
J. Endocrinol., October 1, 2009; 203(1): 99 - 110.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. R. Kim, H. S. Choi, J. W. Yang, B. C. Park, J.-A. Kim, and K. W. Kang
Enhancement of vascular endothelial growth factor-mediated angiogenesis in tamoxifen-resistant breast cancer cells: role of Pin1 overexpression
Mol. Cancer Ther., August 1, 2009; 8(8): 2163 - 2171.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
L. M. Arendt, T. L. Grafwallner-Huseth, and L. A. Schuler
Prolactin-Growth Factor Crosstalk Reduces Mammary Estrogen Responsiveness Despite Elevated ER{alpha} Expression
Am. J. Pathol., March 1, 2009; 174(3): 1065 - 1074.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
J. M. Cline and C. E. Wood
The Mammary Glands of Macaques
Toxicol Pathol, December 1, 2008; 36(7_suppl): 130S - 141S.
[Abstract] [Full Text] [PDF]

Home page
 Cold Spring Harb Symp Quant BiolHome page
M.-L. Asselin-Labat, F. Vaillant, M. Shackleton, T. Bouras, G.J. Lindeman, and J.E. Visvader
Delineating the Epithelial Hierarchy in the Mouse Mammary Gland
Cold Spring Harb Symp Quant Biol, November 19, 2008; (2008) sqb.2008.73.020v2.
[Abstract] [PDF]

Home page
 Cancer Res.Home page
L. A. Helguero, K. Lindberg, C. Gardmo, T. Schwend, J.-A. Gustafsson, and L.-A. Haldosen
Different Roles of Estrogen Receptors {alpha} and {beta} in the Regulation of E-Cadherin Protein Levels in a Mouse Mammary Epithelial Cell Line
Cancer Res., November 1, 2008; 68(21): 8695 - 8704.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
H. K. Choi, S. H. Roh, H. G. Kim, E. H. Han, H. G. Jeong, and K. W. Kang
Enhanced expression of aromatase in p53-inactivated mammary epithelial cells
Endocr. Relat. Cancer, March 1, 2008; 15(1): 139 - 147.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
M A Thorat, C Marchio, A Morimiya, K Savage, H Nakshatri, J S Reis-Filho, and S Badve
Forkhead box A1 expression in breast cancer is associated with luminal subtype and good prognosis
J. Clin. Pathol., March 1, 2008; 61(3): 327 - 332.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. C. Harrell, W. W. Dye, D. M.E. Harvell, M. Pinto, P. Jedlicka, C. A. Sartorius, and K. B. Horwitz
Estrogen Insensitivity in a Model of Estrogen Receptor Positive Breast Cancer Lymph Node Metastasis
Cancer Res., November 1, 2007; 67(21): 10582 - 10591.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
M J Meyer, R P Rhoads, A V Capuco, E E Connor, A Hummel, Y R Boisclair, and M E Van Amburgh
Ontogenic and nutritional regulation of steroid receptor and IGF-I transcript abundance in the prepubertal heifer mammary gland
J. Endocrinol., October 1, 2007; 195(1): 59 - 66.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Feng, D. Manka, K.-U. Wagner, and S. A. Khan
Estrogen receptor-{alpha} expression in the mammary epithelium is required for ductal and alveolar morphogenesis in mice
PNAS, September 11, 2007; 104(37): 14718 - 14723.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Badve, D. Turbin, M. A. Thorat, A. Morimiya, T. O. Nielsen, C. M. Perou, S. Dunn, D. G. Huntsman, and H. Nakshatri
FOXA1 Expression in Breast Cancer Correlation with Luminal Subtype A and Survival
Clin. Cancer Res., August 1, 2007; 13(15): 4415 - 4421.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Ishida, W. Takahashi, S. Itoh, S. Shimodaira, S. Maeda, and J. Arita
Estrogen Actions on Lactotroph Proliferation Are Independent of a Paracrine Interaction with Other Pituitary Cell Types: A Study Using Lactotroph-Enriched Cells
Endocrinology, July 1, 2007; 148(7): 3131 - 3139.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. Ciarloni, S. Mallepell, and C. Brisken
Amphiregulin is an essential mediator of estrogen receptor {alpha} function in mammary gland development
PNAS, March 27, 2007; 104(13): 5455 - 5460.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. Harris, P. M. Stanford, K. Sutherland, S. R. Oakes, M. J. Naylor, F. G. Robertson, K. D. Blazek, M. Kazlauskas, H. N. Hilton, S. Wittlin, et al.
Socs2 and Elf5 Mediate Prolactin-Induced Mammary Gland Development
Mol. Endocrinol., May 1, 2006; 20(5): 1177 - 1187.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Mallepell, A.ée Krust, P. Chambon, and C. Brisken
Paracrine signaling through the epithelial estrogen receptor {alpha} is required for proliferation and morphogenesis in the mammary gland
PNAS, February 14, 2006; 103(7): 2196 - 2201.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S.-Q. Kuang, L. Liao, S. Wang, D. Medina, B. W. O'Malley, and J. Xu
Mice Lacking the Amplified in Breast Cancer 1/Steroid Receptor Coactivator-3 Are Resistant to Chemical Carcinogen-Induced Mammary Tumorigenesis
Cancer Res., September 1, 2005; 65(17): 7993 - 8002.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Munoz-de-Toro, C. M. Markey, P. R. Wadia, E. H. Luque, B. S. Rubin, C. Sonnenschein, and A. M. Soto
Perinatal Exposure to Bisphenol-A Alters Peripubertal Mammary Gland Development in Mice
Endocrinology, September 1, 2005; 146(9): 4138 - 4147.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
M. D. Sternlicht, S. W. Sunnarborg, H. Kouros-Mehr, Y. Yu, D. C. Lee, and Z. Werb
Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via ADAM17-dependent shedding of epithelial amphiregulin
Development, September 1, 2005; 132(17): 3923 - 3933.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
K. B.R. Ewan, H. A. Oketch-Rabah, S. A. Ravani, G. Shyamala, H. L. Moses, and M. H. Barcellos-Hoff
Proliferation of Estrogen Receptor-{alpha}-Positive Mammary Epithelial Cells Is Restrained by Transforming Growth Factor-{beta}1 in Adult Mice
Am. J. Pathol., August 1, 2005; 167(2): 409 - 417.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
E E Connor, D L Wood, T S Sonstegard, A F da Mota, G L Bennett, J L Williams, and A V Capuco
Chromosomal mapping and quantitative analysis of estrogen-related receptor alpha-1, estrogen receptors alpha and beta and progesterone receptor in the bovine mammary gland
J. Endocrinol., June 1, 2005; 185(3): 593 - 603.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Jia, C. Qi, Z. Zhang, Y. T. Zhu, S. M. Rao, and Y.-J. Zhu
Peroxisome Proliferator-activated Receptor-binding Protein Null Mutation Results in Defective Mammary Gland Development
J. Biol. Chem., March 18, 2005; 280(11): 10766 - 10773.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Omoto, O. Imamov, M. Warner, and J.-A. Gustafsson
Estrogen receptor {alpha} and imprinting of the neonatal mouse ventral prostate by estrogen
PNAS, February 1, 2005; 102(5): 1484 - 1489.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
M. H. Herynk and S. A. W. Fuqua
Estrogen Receptor Mutations in Human Disease
Endocr. Rev., December 1, 2004; 25(6): 869 - 898.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
H. Parmar and G. R Cunha
Epithelial-stromal interactions in the mouse and human mammary gland in vivo
Endocr. Relat. Cancer, September 1, 2004; 11(3): 437 - 458.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
H. Y. Shi, J. P. Lydon, and M. Zhang
Hormonal Defect in Maspin Heterozygous Mice Reveals a Role of Progesterone in Pubertal Ductal Development
Mol. Endocrinol., September 1, 2004; 18(9): 2196 - 2207.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Qi, P. Kashireddy, Y. T. Zhu, S. M. Rao, and Y.-J. Zhu
Null Mutation of Peroxisome Proliferator-activated Receptor-interacting Protein in Mammary Glands Causes Defective Mammopoiesis
J. Biol. Chem., August 6, 2004; 279(32): 33696 - 33701.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. Cheng, Z. Weihua, M. Warner, and J.-A. Gustafsson
Inaugural Article: Estrogen receptors ER{alpha} and ER{beta} in proliferation in the rodent mammary gland
PNAS, March 16, 2004; 101(11): 3739 - 3746.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Naaz, S. Yellayi, M. A. Zakroczymski, D. Bunick, D. R. Doerge, D. B. Lubahn, W. G. Helferich, and P. S. Cooke
The Soy Isoflavone Genistein Decreases Adipose Deposition in Mice
Endocrinology, August 1, 2003; 144(8): 3315 - 3320.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. V. Lee, P. Zhang, M. Ivanova, S. Bonnette, S. Oesterreich, J. M. Rosen, S. Grimm, R. C. Hovey, B. K. Vonderhaar, C. R. Kahn, et al.
Developmental and Hormonal Signals Dramatically Alter the Localization and Abundance of Insulin Receptor Substrate Proteins in the Mammary Gland
Endocrinology, June 1, 2003; 144(6): 2683 - 2694.
[Abstract] [Full Text] [PDF]

Home page
 J DAIRY SCIHome page
S. D. K. Berry, P. M. Jobst, S. E. Ellis, R. D. Howard, A. V. Capuco, and R. M. Akers
Mammary Epithelial Proliferation and Estrogen Receptor {alpha} Expression in Prepubertal Heifers: Effects of Ovariectomy and Growth Hormone
J Dairy Sci, June 1, 2003; 86(6): 2098 - 2105.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2002 by The Endocrine Society