Edison Biotechnology Institute, Ohio University, Athens, OH, 45701, USA.
Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, 45701, USA.
Pituitary. 2021 Jun;24(3):384-399. doi: 10.1007/s11102-020-01118-z. Epub 2021 Jan 12.
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.
大多数研究都是在单一组织中检查生长激素（GH）的转录反应，因此，本研究对接受重组人生长激素（rhGH）治疗的生长激素缺乏症（GHKO）小鼠的三个胰岛素敏感组织进行了 RNA-seq 分析。
GHKO 小鼠每天接受 rhGH 或载体注射 5 天，最后一次注射后 4 小时收集脂肪、肝脏和肌肉组织。从组织中分离 RNA 并进行测序。对 GH 处理和载体处理之间差异表达的基因进行了进一步分析。进行了富集分析和拓扑感知途径分析。
用 rhGH 治疗的 GHKO 小鼠表现出预期的表型改变，体重、脂肪、体液、肝脏和肌肉质量增加，血清 IGF-1 和胰岛素水平升高。在所有三种组织中，有 55 个基因差异表达，包括经典的 GH 靶基因 Igf1、Igfals 和 Cish。富集分析证实了某些组织中的经典 GH 反应，如细胞增殖、代谢和纤维化。JAK/STAT 途径是所有三种组织中唯一显著改变的途径。
正如预期的那样，GH 引起了许多已知靶基因的表达变化，尽管也确定了新的候选 GH 靶基因。与脂肪组织相比，肝脏和肌肉组织对 GH 的敏感性更高，因为差异表达基因和显著改变的途径数量更多，但脂肪组织仍然具有特征性的 GH 反应。GH 治疗 5 天后在所有三种组织中发现的变化多样性突出了 GH 在其靶组织中的多种作用。
