For patients with certain types of pituitary adenoma, surgery — often followed by radiotherapy — has been the only option. But now, Heaney et al. have identified the nuclear hormone receptor PPAR-γ (peroxisome proliferator-activated receptor-γ) — which functions as a ligand-dependent transcription factor — as a potential therapeutic target that could provide an alternative to the surgeon's knife.

The most common pituitary tumours do not secrete hormones (non-functioning adenomas) and there are no effective drug therapies for these tumours. In addition, a subset of patients with prolactin (PRL)- and growth-hormone (GH)-secreting tumours do not respond to the commonly used dopamine agonists or somatostatin analogues. Patients with both types of tumour require surgery. Most patients are diagnosed only when hormonal hypersecretory syndromes have become evident or when their tumours have reached more than 1 cm in diameter, and surgical resection of these macroadenomas has a cure rate of only ∼30%. Surgery also risks damage to surrounding normal pituitary tissue, leading to hormonal deficiency (which is an important cause of co-morbidity).

Expression of PPAR-γ is upregulated in prostate, breast and colorectal tumours, and treatment with PPAR-γ-activating thiazolidinediones (TZDs, such as rosiglitazone and troglitazone) inhibits the growth of such tumours in vitro and in mouse models. The authors of this study have now shown that PPAR-γ is also highly expressed in human pituitary tumour tissue compared with normal pituitary tissue, and that TZDs inhibit growth of these tumours in vitro and in vivo.

Treatment of human non-functioning, rat GH3 (PRL- and GH-secreting) or mouse αT3 (gonadotroph) pituitary tumour cells with rosiglitazone or troglitazone led to G0–G1 cell-cycle arrest and decreased the number of cells in S phase. This was shown to be associated with a decrease in the level of phosphorylated retinoblastoma protein. Treatment with TZDs also increased tumour-cell apoptosis in vitro in a dose-dependent manner, which correlated with an increase in the level of the pro-apoptotic protein Bax.

In an in vivo model, treatment with rosiglitazone was shown to inhibit tumour growth in athymic nude mice that were inoculated subcutaneously with GH3 cells — tumour weight was markedly lower in treated mice compared with control mice after 4 weeks. Importantly, rosiglitazone could also inhibit the growth of already established tumours of αT3 cells.

As oral rosiglitazone has already been approved for use in humans in the United States (for the treatment of type-2 diabetes), this drug could be safer and more effective than going under the knife for patients with non-functioning adenomas or with hormone-secreting pituitary tumours that are unresponsive to current drug therapies.