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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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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Funding

This work was supported in part by a Grant (Grant for Growth Innovation, GGI) from Merck KGaA, Darmstadt, Germany, by NIH Grant #AG059779, Ohio University Heritage College of Osteopathic Medicine, The Diabetes Institute at Ohio University, and the State of Ohio’s Eminent Scholar Program that includes a gift from Milton and Lawrence Goll.

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Author notes

  1. Darlene E. Berryman and Edward O. List: co-senior authors.

Authors and Affiliations

  1. Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA

    Jonathan A. Young, Mat Buchman, Silvana Duran-Ortiz, Colin Kruse, Stephen Bell, John J. Kopchick, Darlene E. Berryman & Edward O. List

  2. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, 45701, USA

    Jonathan A. Young, Stephen Bell, John J. Kopchick & Darlene E. Berryman

  3. The Diabetes Institute at Ohio University, Ohio University, Athens, OH, 45701, USA

    Darlene E. Berryman & Edward O. List

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Contributions

EL, DB, and JK contributed to the study conception and design. Material preparation, data collection and analysis were performed by JY, MB, CK, SB, and SD-O. The first draft of the manuscript was written by JY and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Edward O. List.

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Young, J.A., Buchman, M., Duran-Ortiz, S. et al. Transcriptome profiling of insulin sensitive tissues from GH deficient mice following GH treatment. Pituitary 24, 384–399 (2021). https://doi.org/10.1007/s11102-020-01118-z

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