PPARα modulates the TSH β-subunit mRNA expression in thyrotrope TαT1 cells and in a mouse model

Scope Fasting leads to a significant downregulation of the hypothalamus-pituitary-thyroid axis, and peroxisome proliferator-activated receptor (PPAR) is a key transcription factor in mediating a magnitude of adaptive responses to fasting. In this study, we examined the role of PPAR in regulation of the hypothalamus-pituitary-thyroid axis. Methods and results Thyroid-stimulating hormone -subunit (TSH) mRNA abundance was being reduced in response to treatment of TT1 cells with PPAR agonists (p < 0.05), indicating an inhibitory transcriptional regulation of TSH by PPAR. As expected, fasting significantly downregulated TSH mRNA expression in a two-factorial study with fed or fasted wild-type (WT) and PPAR knockout mice (p < 0.05). In contrast to the in vitro data, fasted PPAR knockout mice revealed lower mRNA concentrations of pituitary TSH (64%) and TSH-regulated thyroid genes, and lower plasma concentrations of thyroxine (T4, 25%), triiodothyronine (T3, 25%), free T4 (60%), and free T3 (35%) than fasted WT mice (p < 0.05). Those differences were not observed in fed mice. Conclusions Data from thyrotrope cells revealed that PPAR could contribute to the fasting-associated downregulation of the TSH mRNA expression. In a mouse model, fasting led to a significant reduction in TSH mRNA level, but unexpectedly this effect was stronger in mice lacking PPAR than in WT mice.