Patterns of thyroid hormone receptor expression in zebrafish and generation of a novel model of resistance to thyroid hormone action

2016 ◽  
Vol 424 ◽  
pp. 102-117 ◽  
Author(s):  
Federica Marelli ◽  
Silvia Carra ◽  
Maura Agostini ◽  
Franco Cotelli ◽  
Robin Peeters ◽  
...  
2003 ◽  
Vol 284 (1) ◽  
pp. E36-E46 ◽  
Author(s):  
Peter M. Sadow ◽  
Olivier Chassande ◽  
Karine Gauthier ◽  
Jacques Samarut ◽  
Jianming Xu ◽  
...  

Isoforms of the thyroid hormone receptor ( TR) α and TRβ genes mediate thyroid hormone action. How TR isoforms modulate tissue-specific thyroid hormone (TH) action remains largely unknown. The steroid receptor coactivator-1 (SRC-1) is among a group of transcriptional coactivator proteins that bind to TRs, along with other members of the nuclear receptor superfamily, and modulate the activity of genes regulated by TH. Mice deficient in SRC-1 possess decreased tissue responsiveness to TH and many steroid hormones; however, it is not known whether or not SRC-1-mediated activation of TH-regulated gene transcription in peripheral tissues, such as heart and liver, is TR isoform specific. We have generated mice deficient in TRα and SRC-1, as well as in TRβ and SRC-1, and investigated thyroid function tests and effects of TH deprivation and TH treatment compared with wild-type (WT) mice or those deficient in either TR or SRC-1 alone. The data show that 1) in the absence of TRα or TRβ, SRC-1 is important for normal growth; 2) SRC-1 modulates TRα and TRβ effects on heart rate; 3) two new TRβ-dependent markers of TH action in the liver have been identified, osteopontin (upregulated) and glutathione S-transferase (downregulated); and 4) SRC-1 may mediate the hypersensitivity to TH seen in liver of TRα-deficient mice.


2021 ◽  
Author(s):  
Marcus Heldmann ◽  
Krishna Chatterjee ◽  
Carla Moran ◽  
Berenike Rogge ◽  
Julia Steinhardt ◽  
...  

Background: Thyroid hormone action is mediated by two forms of thyroid hormone receptors (α,β) with differential tissue distribution. Thyroid hormone receptor β (TRβ) mutations lead to resistance to thyroid hormone action in tissues predominantly expressing the β form of the receptor (pituitary, liver). This study seeks to identify effects of mutant TRβ on pituitary size. Methods: High-resolution 3D T1-weighted magnetic resonance images were acquired in 19 patients with RTHβ in comparison to 19 healthy matched controls. Volumetric measurements of the pituitary gland were performed independently and blinded by four different raters (two neuroradiologists, one neurologist, one neuroscientist). Results: Patients with mutant TRβ (Resistance to Thyroid Hormone β,RΤΗβ) showed elevated fT3/4 levels with normal TSH levels, whereas healthy controls showed normal thyroid hormone levels. Imaging revealed smaller pituitary size in RTHβ patients in comparison to healthy controls (F(1,35)=7.05, p=0.012, partial η2 =0.17). Conclusion: RTHβ subjects have impaired sensitivity to thyroid hormones, along with decreased size of the pituitary gland.


2015 ◽  
Vol 35 (8) ◽  
pp. 895-901 ◽  
Author(s):  
Octavio Sánchez-García ◽  
Julia Rodríguez-Castelán ◽  
Margarita Martínez-Gómez ◽  
Estela Cuevas ◽  
Francisco Castelán

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