Next Article in Journal
Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer
Next Article in Special Issue
GH/IGF-1 Signaling and Current Knowledge of Epigenetics; a Review and Considerations on Possible Therapeutic Options
Previous Article in Journal
Genome-Wide Analysis of CCA1-Like Proteins in Soybean and Functional Characterization of GmMYB138a
Previous Article in Special Issue
Manipulation of the Growth Hormone-Insulin-Like Growth Factor (GH-IGF) Axis: A Treatment Strategy to Reverse the Effects of Early Life Developmental Programming
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(10), 2046; doi:10.3390/ijms18102046

Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis

1
Novo Nordisk A/S, Haemophilia Research, Maaloev 2760, Denmark
2
Department of Gastroenterology, Herlev Hospital, Herlev 2730, Denmark
3
Pila Pharma AB, 20512 Malmö, Sweden
4
Edison Biotechnology Institute & Department of Biomedical Sciences, HCOM, Ohio University, Athens, OH 45701, USA
*
Author to whom correspondence should be addressed.
Received: 28 August 2017 / Revised: 14 September 2017 / Accepted: 20 September 2017 / Published: 23 September 2017
(This article belongs to the Special Issue Growth Hormone: Therapeutic Possibilities)
View Full-Text   |   Download PDF [4282 KB, uploaded 25 September 2017]   |  

Abstract

Growth hormone (GH) resistance may develop as a consequence of inflammation during conditions such as inflammatory bowel disease, encompassing ulcerative colitis (UC). However, the specific role of the GH–insulin growth factor (IGF)-1-axis and/or the functional consequences of GH resistance in this condition are unclear. In situ hybridization targeting the GH receptor (GHR) and relevant transcriptional analyses were performed in patients with UC and in IL-10 knock-out mice with piroxicam accelerated colitis (PAC). Using cultured primary epithelial cells, the effects of inflammation on the molecular mechanisms governing GH resistance was verified. Also, the therapeutic potential of GH on mucosal healing was tested in the PAC model. Inflammation induced intestinal GH resistance in UC and experimental colitis by down-regulating GHR expression and up-regulating suppressor of cytokine signalling (SOCS) proteins. These effects are driven by pro-inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6) as confirmed using primary epithelial cells. Treatment of experimental colitis with GH increased IGF-1 and body weight of the mice, but had no effects on colonic inflammation or mucosal healing. The high transcriptional similarity between UC and experimental colitis accentuates the formation of intestinal GH resistance during inflammation. Inflammation-induced GH resistance not only impairs general growth but induces a state of local resistance, which potentially impairs the actions of GH on mucosal healing during colitis when using long-acting GH therapy. View Full-Text
Keywords: experimental colitis; GH resistance; GHR; IGF-1; inflammation; long acting human GH; ulcerative colitis experimental colitis; GH resistance; GHR; IGF-1; inflammation; long acting human GH; ulcerative colitis
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Soendergaard, C.; Kvist, P.H.; Thygesen, P.; Reslow, M.; Nielsen, O.H.; Kopchick, J.J.; Holm, T.L. Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis. Int. J. Mol. Sci. 2017, 18, 2046.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top