Thyroid-specific PPARγ deletion is benign in the mouse.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is widely expressed at low levels and regulates many physiological processes. In mice and humans, there is evidence that PPARg can function as a tumor suppressor. A PAX8-PPAR gamma fusion protein (PPFP) is oncogenic in a subset of thyroid cancers, suggesting that inhibition of endogenous PPAR gamma function by the fusion protein could contribute to thyroid oncogenesis. However, the function of PPAR gamma within thyrocytes has never been directly tested. Therefore, we have created a thyroid-specific genetic knockout of murine Pparg and have studied thyroid biology in these mice. Thyroid size and histology, the expression of thyroid-specific genes, and serum T4 levels all are unaffected by loss of thyroidal PPAR gamma expression. PPFP thyroid cancers have increased activation of AKT, and mice with thyroid-specific expression of PPFP combined with thyroid-specific loss of PTEN (a negative regulator of AKT) develop thyroid cancer. Therefore we created mice with combined thyroid-specific deletions of Pparg and Pten to test if there is oncogenic synergy between these deletions. Pten deletion alone results in benign thyroid hyperplasia, and this is unchanged when combined with deletion of Pparg. We conclude that, at least in the contexts studied, thyrocyte PPARg does not play a significant role in the development or function of the thyroid and does not function as a tumor suppressor.