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Department of Animal Science, Cornell University, Ithaca, New York 14850, USA
1 Bovine Functional Genomics Lab, USDA-ARS, Beltsville, Maryland 20705, USA
(Requests for offprints should be addressed to Y R Boisclair who is now at 259 Morrison Hall, Cornell University, Ithaca New York 14853, USA; Email: yrb1{at}cornell.edu)
(M J Meyer is now at Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, National Institutes of Health, Building 37, Room 1108, 37 Convent Drive, Bethesda, Maryland 20892-4254, USA; M E Van Amburgh is now at 272 Morrison Hall, Cornell University, Ithaca, New York 14853, USA; Email: mev1{at}cornell.edu)
Ovaries are absolutely required for development of the mammary parenchyma (PAR) in cattle, reflecting estrogen-dependent epithelial cell proliferation. However, the estrogen receptor (ER) that mediates the mammary estrogen effects, ER
, is absent in proliferating epithelial cells. In the mouse, this discrepancy is explained in part by the ability of the mammary fat pad (MFP) to synthesize epithelial cell mitogens such as IGF-I in response to estrogen. Consistent with a similar role for the bovine MFP, 30% of its fibroblasts and adipocytes were immunoreactive for ER in prepubertal dairy heifers. To assess estrogen-dependent gene expression in the MFP, 16 prepubertal dairy heifers were randomly assigned to a 2x2 factorial. The first factor was ovarian status, with heifers undergoing bilateral ovariectomy or left intact at 4.6 months of age. The second factor was applied 30 days after surgery and consisted of injection of estrogen or excipient. After 3 days of injection, heifers were administered an intrajugular bolus of bromodeoxyuridine (BrdU) and slaughtered 2 h later. The estrogen injection, but not ovarian status, caused significant increases in the fraction of epithelial cells labeled with BrdU and produced tissue-specific effects on gene expression. In the PAR, estrogen injection increased IGF-I gene expression by twofold despite reductions of 50% or more in ER mRNA abundance and the fraction of epithelial cells immunoreactive for ER. The estrogen-dependent increase in IGF-I mRNA was greater in the MFP, presumably because estrogen failed to downregulate ER expression in this mammary compartment. Finally, estrogen-responsiveness of the MFP appears unique among the bovine fat depots as estrogen injection did not induce IGF-I expression in its s.c. counterpart. Our data demonstrate that the bovine MFP is highly responsive to exogenous estrogen, consistent with a role for this tissue compartment in communicating its effects on epithelial cell proliferation.
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  S. R Thorn, S. Purup, M. Vestergaard, K. Sejrsen, M. J Meyer, M. E Van Amburgh, and Y. R Boisclair Regulation of mammary parenchymal growth by the fat pad in prepubertal dairy heifers: role of inflammation-related proteins J. Endocrinol., March 1, 2008; 196(3): 539 - 546. [Abstract] [Full Text] [PDF]
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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]
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 S. R. Thorn, M. J. Meyer, M. E. Van Amburgh, and Y. R. Boisclair Effect of Estrogen on Leptin and Expression of Leptin Receptor Transcripts in Prepubertal Dairy Heifers J Dairy Sci, August 1, 2007; 90(8): 3742 - 3750. [Abstract] [Full Text] [PDF]
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E. E. Connor, M. J. Meyer, R. W. Li, M. E. Van Amburgh, Y. R. Boisclair, and A. V. Capuco Regulation of Gene Expression in the Bovine Mammary Gland by Ovarian Steroids J Dairy Sci, June 1, 2007; 90(13_suppl): E55 - E65. [Abstract] [Full Text] [PDF]
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