Consumption of ergot alkaloid-containing tall fescue grass impairs several metabolic, vascular, growth, and reproductive processes in cattle, collectively producing a clinical condition known as “fescue toxicosis.” Despite the apparent association between pituitary function and these physiological parameters, including depressed serum prolactin; no reports describe the effect of fescue toxicosis on pituitary genomic expression profiles. To identify candidate regulatory mechanisms, we compared the global and selected targeted mRNA expression patterns of pituitaries collected from beef steers that had been randomly assigned to undergo summer-long grazing (89 to 105 d) of a high-toxic endophyte-infected tall fescue pasture (HE; 0.746 μg/g ergot alkaloids; 5.7 ha; n = 10; BW = 267 ± 14.5 kg) or a low-toxic endophyte tall fescue–mixed pasture (LE; 0.023 μg/g ergot alkaloids; 5.7 ha; n = 9; BW = 266 ± 10.9 kg). As previously reported, in the HE steers, serum prolactin and body weights decreased and a potential for hepatic gluconeogenesis from amino acid-derived carbons increased. In this manuscript, we report that the pituitaries of HE steers had 542 differentially expressed genes (P < 0.001, false discovery rate ≤ 4.8%), and the pattern of altered gene expression was dependent (P < 0.001) on treatment. Integrated Pathway Analysis revealed that canonical pathways central to prolactin production, secretion, or signaling were affected, in addition to those related to corticotropin-releasing hormone signaling, melanocyte development, and pigmentation signaling. Targeted RT-PCR analysis corroborated these findings, including decreased (P < 0.05) expression of DRD2, PRL, POU1F1, GAL, and VIP and that of POMC and PCSK1, respectively. Canonical pathway analysis identified HE-dependent alteration in signaling of additional pituitary-derived hormones, including growth hormone and GnRH. We conclude that consumption of endophyte-infected tall fescue alters the pituitary transcriptome profiles of steers in a manner consistent with their negatively affected physiological parameters.

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Notes/Citation Information

Published in PLOS ONE, v. 12, 9, e0184612, p. 1-17.

© 2017 Li et al.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Funding Information

This work is supported by a United States Department of Agriculture-Agricultural Research Service Cooperative Agreement (JCM) and by the National Institute of Food and Agriculture, U.S. Department of Agriculture, Hatch project No. KY007095 (JCM, PB).

Related Content

This is publication No. 17-07-076 of the Kentucky Agricultural Experiment Station and is published with approval of the Director.

All relevant data are within the paper and its Supporting Information files, except for the .cel files which are available from GEO (http://www.ncbi.nlm.nih.gov/geo/) as accession no. GSE62570.

journal.pone.0184612.s001.docx (15 kB)
S1 Fig. The sequences of the real-time RT-PCR products (5’ to 3’ orientation).

journal.pone.0184612.s002.docx (145 kB)
S2 Fig. Principle component analysis of microarray transcriptome analysis of 16 pituitary samples from steers grazing high- (HE, n = 8, red dots) or low- (LE, n = 8, blue dots) endophyte-infected forages.

journal.pone.0184612.s003.docx (138 kB)
S3 Fig. Hierarchical cluster analysis of the 542 “focus” genes selected as differentially expressed (ANOVA P-values of < 0.001 and false discovery rates of ≤ 5%) by the pituitary of steers grazing high- (HE, n = 8) vs. low- (LE, n = 8) endophyte-infected forages.

journal.pone.0184612.s004.docx (19 kB)
S1 Table. Primer sets used for quantitative real-time RT-PCR analysis of the selected differentially expressed genes and reference genes.

journal.pone.0184612.s005.docx (78 kB)
S2 Table. List of differentially expressed pituitary genes (P < 0.001, 542 genes) collected from steers grazing high- (HE, n = 8) or low- (LE, n = 8) endophyte-infected forages.

journal.pone.0184612.s006.docx (13 kB)
S3 Table. List of selected genes involved in prolactin or POMC/ACTH expression expressed by pituitaries collected from steers grazing high- (HE, n = 8) or low- (LE, n = 8) endophyte-infected forages.