Endocrine Abstracts (2004) 7 OC25

PPAR gamma expression in pituitary tumours

MN Emery1, C Merulli1, SE Bonner2, AM Nanzer1, M Musat1, M Galloway3, AB Grossman1 & M Korbonits1

1Department of Endocrinology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK; 2Department of Breast and Endocrine Surgery, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK; 3Department of Neuropathology, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen's Square, London, UK.

It has been reported that both normal pituitary and pituitary tumours express PPAR gamma, a nuclear hormone receptor, the expression being much more abundant in pituitary tumours. It has also been suggested that PPAR gamma agonists, such as the thiazolidenediones, could be used as a therapeutic option for pituitary tumours. In order to investigate this further, 'Real time' PCR was used to assess PPAR gamma RNA expression, and Western blotting and immunohistochemistry was used to study its protein expression, in 48 human pituitary tumours. The effect of 48h treatment with rosiglitazone in 10-4M - 10-10M concentration on GH3 cell proliferation was assessed by [3H]-thymidine incorporation.

We were able to detect PPAR gamma mRNA expression in all types of pituitary adenomas. Protein expression of PPAR gamma using Western blotting techniques showed over-expression in tumours compared with normals. However, very little staining was observed with immunohistochemistry, and no difference was detectable between controls and tumours. Rosiglitazone at 10-5M concentration inhibited cell proliferation (control: 15147 counts per minute plus/minus 1358 SEM vs treated: 9619 counts per minute plus/minus 698 SEM, P=0.0014) while lower concentrations showed no significant effect. Following withdrawal of rosiglitazone treatment cells recovered to control proliferation rate within 48h.

In conclusion, PPAR gamma appears to be over-expressed in pituitary tumours at the RNA level and protein level, at least by Western blotting, although this was not obvious using immunohistochemistry. Treatment with the PPAR gamma agonist rosiglitazone demonstrated an antiproliferative effect, but only at relatively high doses. More potent PPAR gamma agonists may have a place in the future management of pituitary tumours.

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