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Title: REGULATION OF GENE EXPRESSION IN THE BOVINE MAMMARY GLAND BY OVARIAN STEROIDS

Author
item Connor, Erin
item MEYER, M - NIH CANCER INSTITUTE
item Li, Robert
item VAN AMBURGH, M - CORNELL UNIVERSITY
item BOISCLAIR, Y - CORNELL UNIVERSITY
item Capuco, Anthony

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/26/2006
Publication Date: 6/1/2007
Citation: Connor, E.E., Meyer, M.J., Li, R.W., Van Amburgh, M.E., Boisclair, Y.R., Capuco, A.V. 2007. Regulation of gene expression in the bovine mammary gland by ovarian steroids. Journal of Dairy Science. 90 (E. Suppl):E55-E65.

Interpretive Summary: Estrogen and progesterone, produced by the ovaries, play critical roles in the development and function of the mammary gland. The goal of this review is to briefly summarize our current understanding of estrogen and progesterone’s effects on mammary function and gene expression, and to highlight recent studies of the bovine mammary gland using molecular and genomic approaches. Continuing studies using advanced molecular techniques should assist in characterizing the complex regulation of mammary function at the gene level. Ultimately, knowledge of gene regulation in the mammary gland should facilitate development of methods to increase milk yield and lactation persistency of dairy cattle, reduce the length of the dry period between successive lactations, and improve efficiency of dairy production.

Technical Abstract: It is well established that estrogen is required for mammary epithelial cell proliferation and ductal development in the growing animal, and that lobuloalveolar development during gestation is dependent upon progesterone. Effects of these steroid hormones on gene expression in the mammary gland are mediated primarily by their respective nuclear hormone receptors that function as hormone-bound transcription factors. To gain insight into how estrogen and progesterone regulate mammary gland growth and function in cattle, we and others have characterized the expression patterns of their cognate nuclear hormone receptors in bovine mammary gland throughout development, pregnancy and lactation. This work has identified a lack of expression of estrogen receptor ' and a greater abundance of progesterone receptor during lactation in bovine mammary gland versus the rodent gland. We speculate that interactions among the estrogen receptor isoforms that regulate progesterone receptor expression may contribute to these species differences. Further, demonstrated expression of substantial quantities of estrogen receptor within the prepubertal bovine mammary fat pad, along with coordinated IGF-I expression, suggests this tissue may stimulate parenchymal growth via an estrogen-responsive paracrine mechanism. In addition, the recent availability of bovine genomic sequence information and microarray technologies has permitted the study of global gene expression in the mammary gland in response to the steroid environment. We have identified more than 100 estrogen-responsive genes of which the majority are novel estrogen gene targets. Estrogen-induced changes in gene expression were consistent with increased mammary epithelial cell proliferation, increased extracellular matrix turnover in parenchyma, and increased extracellular matrix deposition in the fat pad. A comparison of estrogen-responsive genes in the mammary glands of humans, mice and cattle suggests considerable variation among species, as well as potential differences in regulatory elements in common estrogen receptor gene targets. Continuing studies using advanced molecular techniques should assist in elucidating the complex regulation of mammary function at the transcript level.