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Transcriptome profiling of insulin sensitive tissues from GH deficient mice following GH treatment.

Authors
  • Young, Jonathan A1, 2
  • Buchman, Mat1
  • Duran-Ortiz, Silvana1
  • Kruse, Colin1
  • Bell, Stephen1, 2
  • Kopchick, John J1, 2
  • Berryman, Darlene E1, 2, 3
  • List, Edward O4, 5
  • 1 Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA.
  • 2 Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, 45701, USA.
  • 3 The Diabetes Institute at Ohio University, Ohio University, Athens, OH, 45701, USA.
  • 4 Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA. [email protected]
  • 5 The Diabetes Institute at Ohio University, Ohio University, Athens, OH, 45701, USA. [email protected]
Type
Published Article
Journal
Pituitary
Publisher
Springer-Verlag
Publication Date
Jun 01, 2021
Volume
24
Issue
3
Pages
384–399
Identifiers
DOI: 10.1007/s11102-020-01118-z
PMID: 33433889
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Most studies that have examined the transcriptional response to GH have been performed with a single tissue. Thus, the current study performed RNASeq across three insulin-sensitive tissues of GH-treated GH deficient (GHKO) mice. GHKO mice were injected with recombinant human GH (hGH) or vehicle daily for 5 days and adipose, liver, and muscle tissues were collected 4 h after the final injection. RNA was isolated from the tissues and sequenced. Genes that were differentially expressed between GH and vehicle treatments were further analyzed. Enrichment analysis and topology-aware pathway analysis were performed. GHKO mice treated with hGH had expected phenotypic alterations, with increased body, fat, fluid, liver, and muscle mass, and increased serum IGF-1 and insulin. 55 Genes were differentially expressed in all three tissues, including the canonical GH targets Igf1, Igfals, and Cish. Enrichment analysis confirmed the canonical GH response in select tissues, such as cell proliferation, metabolism, and fibrosis. The JAK/STAT pathway was the only pathway significantly altered in all three tissues. As expected, GH caused expression changes of many known target genes, although new candidate GH targets were identified. Liver and muscle appear to be more GH sensitive than adipose tissue due to the larger number of DEG and pathways significantly altered, but adipose still has a characteristic GH response. The diversity of changes uncovered in all three tissues after 5 days of GH treatment highlights the multiplicity of GH's effects in its target tissues.

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