PPAR α modulates the TSH β‐subunit m RNA expression in thyrotrope T α T 1 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 ) α is a key transcription factor in mediating a magnitude of adaptive responses to fasting. In this study, we examined the role of PPAR α in regulation of the hypothalamus‐pituitary‐thyroid axis. Methods and results Thyroid‐stimulating hormone β‐subunit ( TSH β) m RNA abundance was being reduced in response to treatment of T α T 1 cells with PPAR α agonists ( p < 0.05), indicating an inhibitory transcriptional regulation of TSH β by PPAR α. As expected, fasting significantly downregulated TSH β m RNA expression in a two‐factorial study with fed or fasted wild‐type ( WT ) and PPAR α knockout mice ( p < 0.05). In contrast to the in vitro data, fasted PPAR α knockout mice revealed lower m RNA concentrations of pituitary TSH β (−64%) and TSH ‐regulated thyroid genes, and lower plasma concentrations of thyroxine ( T 4, −25%), triiodothyronine ( T 3, −25%), free T 4 (−60%), and free T 3 (−35%) than fasted WT mice ( p < 0.05). Those differences were not observed in fed mice. Conclusions Data from thyrotrope cells revealed that PPAR α could contribute to the fasting‐associated downregulation of the TSH β m RNA expression. In a mouse model, fasting led to a significant reduction in TSH β m RNA level, but unexpectedly this effect was stronger in mice lacking PPAR α than in WT mice.