The thyroid hormone receptor-beta agonist GC-1 induces cell proliferation in rat liver and pancreas

Endocrinology. 2006 Jul;147(7):3211-8. doi: 10.1210/en.2005-1561. Epub 2006 Mar 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / pharmacology*
  • Animals
  • Cell Cycle
  • Cell Proliferation
  • Hepatocytes / metabolism
  • Lipids / chemistry
  • Liver / metabolism
  • Liver / pathology*
  • Male
  • Pancreas / metabolism
  • Pancreas / pathology*
  • Phenols / pharmacology*
  • Rats
  • Rats, Inbred F344
  • Rats, Wistar
  • Thyroid Hormone Receptors beta / agonists*
  • Thyroid Hormones / metabolism


  • Acetates
  • GC 1 compound
  • Lipids
  • Phenols
  • Thyroid Hormone Receptors beta
  • Thyroid Hormones