| Title: |
The thyroid hormone receptor-beta agonist GC-1 induces cell proliferation in rat liver and pancreas |
| Authors: |
COLUMBANO, AMEDEO; PIBIRI, MONICA; MUNTONI, SANDRO; LEDDA, GIOVANNA MARIA; DEIDDA M; COSSU C; SCANLAN TS; CHIELLINI G |
| Contributors: |
Columbano, Amedeo; Pibiri, Monica; Deidda, M; Cossu, C; Scanlan, T; Chiellini, G; Muntoni, Sandro; Ledda, GIOVANNA MARIA |
| Publication Year: |
2006 |
| Collection: |
Università degli Studi di Cagliari: UNICA IRIS |
| Description: |
Thyroid hormones regulate cell growth, cell differentiation, and metabolic functions via interaction with the thyroid hormone nuclear receptors (TRs). Recently, a small class of halogen-free high-affinity thyroid hormone agonists has been developed that are highly selective for the TRbeta subtype. Because of the selective hyperthyroidism generated by one of these agonists, GC-1, this compound has the potential to be developed as a new therapeutic agent for the treatment of a variety of metabolic disturbances, including lipid disorders and obesity; thus, it becomes important to determine whether GC-1 has other unknown effects on potential target organs. The purpose of this study was to investigate the effect of GC-1 on cell proliferation in rat liver and pancreas. Rats treated with GC-1 (50 or 100 mug/100 g body weight) were killed at different time points. Hepatic and pancreatic cell proliferation was monitored by immunohistochemical determination of bromodeoxyuridine incorporation. The expression of cell cycle-related genes was analyzed by Northern and Western analysis. The results show that GC-1 strongly stimulates rat hepatocyte proliferation in the absence of tissue injury. Although GC-1-induced hepatocyte proliferation was associated with a rapid increase in cyclin D1 mRNA levels, no change in the expression of c-jun and c-fos was observed. GC-1 also induced massive pancreatic cell proliferation. The results indicate that the TRbeta-selective agonist GC-1 is a strong mitogen for hepatocytes and pancreatic acinar cells. Furthermore, they suggest that the TRbeta receptor is the mediator for the mitogenic activity of thyroid hormone and other thyromimetics. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/PMID:16574785; info:eu-repo/semantics/altIdentifier/wos/WOS:000238312400008; volume:147; firstpage:3211; lastpage:3218; numberofpages:8; journal:ENDOCRINOLOGY; https://hdl.handle.net/11584/103573 |
| DOI: |
10.1210/en.2005-1561 |
| Availability: |
https://hdl.handle.net/11584/103573; https://doi.org/10.1210/en.2005-1561 |
| Accession Number: |
edsbas.C5A1867B |
| Database: |
BASE |