title: PPARα modulates the TSH β-subunit mRNA expression in thyrotrope TαT1 cells and in a mouse model.
abstract: METHODS
  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.
  
  
  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.
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wege
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schutkowski
authors.forename: Bettina
authors.initials: B
authors.lastname: König
authors.forename: Corinna
authors.initials: C
authors.lastname: Brandsch
authors.forename: Matthias
authors.initials: M
authors.lastname: Weiwad
authors.forename: Gabriele I
authors.initials: GI
authors.lastname: Stangl
mesh_terms: D000818:Animals; D002460:Cell Line; D005215:Fasting / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000235:genetics / Q000378:metabolism; D058607:Fibric Acids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000235:genetics; D047493:PPAR alpha / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000235:genetics; D037042:Thyroid Hormone Receptors beta / Q000235:genetics; D052684:Thyrotrophs / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D037322:Thyrotropin, beta Subunit / Q000235:genetics*; D013974:Thyroxine / Q000097:blood / Q000235:genetics; D014284:Triiodothyronine / Q000097:blood / Q000235:genetics
chemical_list: D005230:Fatty Acids, Nonesterified; D058607:Fibric Acids; D047493:PPAR alpha; D011743:Pyrimidines; D012333:RNA, Messenger; D047490:Retinoid X Receptor alpha; D037042:Thyroid Hormone Receptors beta; D037322:Thyrotropin, beta Subunit; D014284:Triiodothyronine; D015287:Neurokinin B; C006253:pirinixic acid; C038393:neuromedin B; C019304:ciprofibrate; D013974:Thyroxine