[HTML][HTML] PPAR-γ receptor ligands: novel therapy for pituitary adenomas

AP Heaney, M Fernando… - The Journal of clinical …, 2003 - Am Soc Clin Investig
AP Heaney, M Fernando, S Melmed
The Journal of clinical investigation, 2003Am Soc Clin Investig
Pituitary tumors cause considerable morbidity due to local invasion, hypopituitarism, or
hormone hypersecretion. In many cases, no suitable drug therapies are available, and
surgical excision is currently the only effective treatment. We show here abundant
expression of nuclear hormone receptor PPAR-γ in all of 39 human pituitary tumors. PPAR-γ
activating thiazolidinediones (TZDs) rosiglitazone and troglitazone induced G0-G1 cell-cycle
arrest and apoptosis in human, rat somatolactotroph, and murine gonadotroph pituitary …
Pituitary tumors cause considerable morbidity due to local invasion, hypopituitarism, or hormone hypersecretion. In many cases, no suitable drug therapies are available, and surgical excision is currently the only effective treatment. We show here abundant expression of nuclear hormone receptor PPAR-γ in all of 39 human pituitary tumors. PPAR-γ activating thiazolidinediones (TZDs) rosiglitazone and troglitazone induced G0-G1 cell-cycle arrest and apoptosis in human, rat somatolactotroph, and murine gonadotroph pituitary tumor cells, and suppressed in vitro hormone secretion. In vivo development and growth of murine somatolactotroph and gonadotroph tumors, generated by subcutaneous injection of prolactin-secreting (PRL-secreting) and growth hormone–secreting (GH-secreting) GH3 cells, luteinizing hormone–secreting (LH-secreting) LβT2 cells, and α-T3 cells, was markedly suppressed in rosiglitazone-treated mice, and serum GH, PRL, and LH levels were attenuated in all treated animals (P < 0.009). These results demonstrate that PPAR-γ is an important molecular target in pituitary adenoma cells and PPAR-γ ligands inhibit tumor cell growth and GH, PRL, and LH secretion in vitro and in vivo. TZDs are proposed as novel oral medications for managing pituitary tumors.
The Journal of Clinical Investigation