TY - JOUR
T1 - The thyroid hormone receptor-β agonist GC-1 induces cell proliferation in rat liver and pancreas
AU - Columbano, Amedeo
AU - Pibiri, Monica
AU - Deidda, Manuela
AU - Cossu, Costanza
AU - Scanlan, Thomas S.
AU - Chiellini, Grazia
AU - Muntoni, Sandro
AU - Ledda-Columbano, Giovanna M.
PY - 2006
Y1 - 2006
N2 - 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 TRβ 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 μg/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 TRβ-selective agonist GC-1 is a strong mitogen for hepatocytes and pancreatic acinar cells. Furthermore, they suggest that the TRβ receptor is the mediator for the mitogenic activity of thyroid hormone and other thyromimetics.
AB - 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 TRβ 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 μg/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 TRβ-selective agonist GC-1 is a strong mitogen for hepatocytes and pancreatic acinar cells. Furthermore, they suggest that the TRβ receptor is the mediator for the mitogenic activity of thyroid hormone and other thyromimetics.
UR - http://www.scopus.com/inward/record.url?scp=33745169031&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745169031&partnerID=8YFLogxK
U2 - 10.1210/en.2005-1561
DO - 10.1210/en.2005-1561
M3 - Article
C2 - 16574785
AN - SCOPUS:33745169031
SN - 0013-7227
VL - 147
SP - 3211
EP - 3218
JO - Endocrinology
JF - Endocrinology
IS - 7
ER -