Rosiglitazone, PPAR-gamma receptor ligand, decreases the viability of rat prolactin-secreting pituitary tumor cells in vitro.
OBJECTIVE
PPAR-gamma is a member of the nuclear receptor superfamily. PPAR-gamma activation is associated with glucose metabolism regulation, adipocyte differentiation, inhibition of macrophage and monocyte activation and anti-angiogenesis. PPAR-gamma 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, PRL- and GH-secreting GH3, LH-secreting LbetaT2 and alpha-T3 cells). TZDs have been demonstrated to induce G0-G1 cell-cycle arrest and apoptosis in human, rat somatolactotroph, murine corticotroph and gonadotroph pituitary tumor cells. In the present study we have investigated for the first time the effects of PPAR-gamma receptor ligand rosiglitazone on the rat estrogens-induced, PRL-secreting pituitary tumor cells in vitro.


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 after the implantation of capsules the rats were sacrificed and pituitary tumors were collected. Tumorous cells were isolated and exposed in the primary culture to rosiglitazone at the concentrations 10(-10) - 10(-4)M for 24 hours. The 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(-4)M significantly decreases the number of viable rat PRL-secreting pituitary tumor cells in vitro.


CONCLUSIONS
These results suggest that PPAR-gamma receptor agonists thiazolidinediones may be useful in the medical treatment of pituitary tumors.
Gruszka
Anna
A
Institute of Endocrinology, Medical University of Lodz, Poland. gruszka.a@op.pl
Kunert-Radek
Jolanta
J
Pawlikowski
Marek
M
D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000494:pharmacology; D004343:Drug Implants; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D047495:PPAR gamma / Q000187:drug effects*; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D004343:Drug Implants; D007004:Hypoglycemic Agents; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D004054:Diethylstilbestrol; D011388:Prolactin