Expression data from bovine liver

Female sex steroid hormones, estradiol-17 (E2) and progesterone (P4) regulate reproductive function and gene expression in a broad range of tissues. Given the central role of the liver in regulating homeostasis including steroid hormone metabolism, we sought to understand how E2-17 and P4 interact to affect global gene expression in liver. Eight ovariectomized cows were randomly assigned to 4 treatment groups applied in a replicated Latin Square design: 1) No hormone supplementation, 2) E2-17 treatment (ear implant), 3) P4 treatment (intravaginal inserts), and 4) E2-17 combined with P4. After 14 d of treatment, liver biopsies were collected, allowing 28 d intervals between periods. Changes in gene expression in the liver biopsies were monitored using Affymetrix bovine-specific arrays. Treatment with E2-17 altered expression of 479 genes, P4 472 genes, and combined treatment significantly altered expression of 468 genes. In total, 578 genes exhibited altered expression including a remarkable number (346 genes) that responded similarly to E2-17, P4, or combined treatment. Additional evidence for similar gene expression effects of E2-17 and/or P4 were: principal component analysis placed almost every treatment array at a substantial distance from control arrays; Venn diagrams indicated overall treatment effects for most regulated genes; clustering analysis indicated the two major clusters had all treatments upregulating (cluster 1; 172 genes) or downregulating (cluster 2: 173 genes) expression. Thus, unexpectedly, common biological pathways are regulated by E2-17 and/or P4 in liver. Future studies are needed to elucidate mechanism(s) responsible for overlapping actions of E2-17 and P4 on the liver transcriptome. KEYWORDS: estradiol, progesterone, global gene expression, liver, cows.

28