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 PPARα in regulation of the hypothalamus-pituitary-thyroid axis.Methods and results:
Thyroid-stimulating hormone β-subunit (TSHβ) mRNA abundance was being reduced in response to treatment of TαT1 cells with PPARα agonists (p < 0.05), indicating an inhibitory transcriptional regulation of TSHβ by PPARα. As expected, fasting significantly downregulated TSHβ mRNA expression in a two-factorial study with fed or fasted wild-type (WT) and PPARα knockout mice (p < 0.05). In contrast to the in vitro data, fasted PPARα knockout mice revealed lower mRNA concentrations of pituitary TSHβ (−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 PPARα could contribute to the fasting-associated downregulation of the TSHβ mRNA expression. In a mouse model, fasting led to a significant reduction in TSHβ mRNA level, but unexpectedly this effect was stronger in mice lacking PPARα than in WT mice.