Thyroid-Specific PPARγ Deletion Is Benign in the Mouse

Peroxisome proliferator-activated receptor γ (PPARγ) is widely expressed at low levels and regulates many physiological processes. In mice and humans, there is evidence that PPARγ can function as a tumor suppressor. A PAX8-PPARγ fusion protein (PPFP) is oncogenic in a subset of thyroid cancers, suggesting that inhibition of endogenous PPARγ function by the fusion protein could contribute to thyroid oncogenesis. However, the function of PPARγ 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 PPARγ 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 PPARγ does not play a significant role in the development or function of the thyroid and does not function as a tumor suppressor.