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Title: Canonical Pathways and Networks Regulated by Estrogen in the Bovine Mammary Glands

Author
item Li, Robert
item Capuco, Anthony

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/15/2008
Publication Date: 2/1/2008
Citation: Li, R.W., Capuco, A.V. 2008. Canonical Pathways and Networks Regulated by Estrogen in the Bovine Mammary Glands. Biomed Central (BMC) Genomics. 8:55-68.

Interpretive Summary: In this study, we conducted a systematic analysis of pathways and genetic networks regulated by estrogen in the bovine mammary gland with emphasis on tissue-specific regulation of estrogen. We identified 2,344 estrogen responsive genes at False Discovery Rate (FDR) <10%. These genes were subjected to pathway and regulatory network analysis using Ingenuity Pathways Analysis software. The canonical pathways significantly regulated by estrogen (P <0.05) included protein ubiquitination, G2/M cell cycle control, IGF1 signaling, N-glycan biosynthesis, sterol biosynthesis, and oxidative phosphorylation. A total of 23 highly significant regulatory networks were identified as estrogen responsive in the bovine mammary gland. The results provided insight into the molecular mechanisms through which estrogen regulates bovine mammary gland growth and development.

Technical Abstract: Many attempts have been made to identify estrogen-responsive genes using high-throughput approaches such as microarray, SAGE, and in silico prediction. However, few studies have systematically analyzed regulatory networks and pathways affected by estrogen. In this report, we analyzed the transcript profiles obtained from sixteen prepubertal heifers in a 2 x 2 factorial experiment with ovarian status (intact or ovariectomized) as the first factor and estrogen treatment as the second (control or estradiol). After 3 days of estrogen treatment, gene expression was evaluated in the parenchyma and fat pad of the bovine mammary gland using a high-density oligonucleotide microarray. The genes significantly regulated by estrogen were subject to pathway and regulatory network analysis using Ingenuity Pathways Analysis software.