Growth hormone-releasing hormone (GHRH) deficiency promotes inflammation-associated carcinogenesis

Sheila Leone, Annalisa Chiavaroli, Lucia Recinella, Valentina Di Valerio, Serena Veschi, Irene Gasparo, Alessandra Bitto, Claudio Ferrante, Giustino Orlando, Roberto Salvatori, Luigi Brunetti

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The somatotropic axis, in addition to its well-known metabolic and endocrine effects, plays a pivotal role in modulation of inflammation. Moreover, growth hormone (GH)-releasing hormone (GHRH) has been involved in the development of various human tumors. In this work we aimed to investigate the consequences of GHRH deficiency on the development of inflammation-associated colon carcinogenesis in a mouse model of isolated GH deficiency due to generalized ablation of the GHRH gene [GHRH knock out (GHRHKO)]. Homozygous GHRHKO (-/-) male mice and wild type (C57/BL6, +/+) male mice as control group, were used. After azoxymetane (AOM)/dextran sodium sulfate (DSS) treatment -/- mice displayed higher Disease Activity Index (DAI) score, and more marked weight loss compared to +/+ animals. Additionally, -/- mice showed a significant increase in total tumors, in particular of large size predominantly localized in distal colon. In colonic tissue of AOM/DSS-treated -/- mice we found the presence of invasive adenocarcinomas, dysplasia and colitis with mucosal ulceration. Conversely, AOM/DSS-treated +/+ mice showed only presence of adenomas, without invasion of sub-mucosa. Treatment with AOM/DSS significantly increased prostaglandin (PG)E2 and 8-iso-PGF levels along with cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α, nuclear factor kappa B (NF-kB) and inducible nitric oxide synthase (iNOS) gene expression, in colon specimens. The degree of increase of all these parameters was more markedly in -/- than +/+ mice. In conclusion, generalized GHRH ablation increases colon carcinogenesis responsiveness in male mice. Whether this results from lack of GH or GHRH remains to be established.

Original languageEnglish (US)
Article number104614
JournalPharmacological Research
StatePublished - Feb 2020


  • Colorectal cancer
  • Growth hormone-releasing hormone knockout
  • Inflammation

ASJC Scopus subject areas

  • Pharmacology


Dive into the research topics of 'Growth hormone-releasing hormone (GHRH) deficiency promotes inflammation-associated carcinogenesis'. Together they form a unique fingerprint.

Cite this