Rosiglitazone, PPAR-γ receptor ligand, decreases the viability of rat prolactin-secreting pituitary tumor cells in vitro

OBJECTIVES : PPAR-γ is a member of the nuclear receptor superfamily. PPAR-γ activation is associated with glucose metabolism regulation, adipocyte diff erentiation, inhibition of macrophage and monocyte activation and anti-angiogenesis. PPAR-γ ligands thiazolidinediones (TZDs) have been shown to inhibit the growth and secretory activity of several rat and murine pituitary tumors in vivo as well as in vitro (ACTH-secreting AtT20, PRLand GH-secreting GH3, LH-secreting LβT2 and α-T3 cells). TZDs have been demonstrated to induce G0–G1 cellcycle arrest and apoptosis in human, rat somatolactotroph, murine corticotroph and gonadotroph pituitary tumor cells. In the present study we have investigated for the fi rst time the eff ects of PPAR-γ receptor ligand rosiglitazone on the rat estrogens-induced, PRL-secreting pituitary tumor cells in vitro. MATERIAL AND METHODS : Four weeks old male Fischer 344 rats were used in the experiment. Pituitary tumors were induced by subcutaneous implantation of capsules containing diethylstilboestrol (DES). Eight weeks aft er the implantation of capsules the rats were sacrifi ced and pituitary tumors were collected. Tumorous cells were isolated and exposed in the primary culture to rosiglitazone at the concentrations 10–10 – 10–4M for 24 hours. Th e cell growth was estimated by the measurement of the cells metabolic activity using the EZ4U system. RESULTS : We have demonstrated that rosiglitazone at the concentrations 10–10 – 10–4M signifi cantly decreases the number of viable rat PRL-secreting pituitary tumor cells in vitro. CONCLUSION : Th ese results suggest that PPAR-γ receptor agonists thiazolidinediones may be useful in the medical treatment of pituitary tumors.