scholarly journals Thyroid hormone action in the absence of thyroid hormone receptor DNA-binding in vivo

2003 ◽  
Vol 112 (4) ◽  
pp. 588-597 ◽  
Author(s):  
Nobuyuki Shibusawa ◽  
Koshi Hashimoto ◽  
Amisra A. Nikrodhanond ◽  
M. Charles Liberman ◽  
Meredithe L. Applebury ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Dna Binding ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hormone Action ◽  
Thyroid Hormone Action

Specificity of thyroid hormone receptor subtype and steroid receptor coactivator-1 on thyroid hormone action

2003 ◽  
Vol 284 (1) ◽  
pp. E36-E46 ◽  
Author(s):  
Peter M. Sadow ◽  
Olivier Chassande ◽  
Karine Gauthier ◽  
Jacques Samarut ◽  
Jianming Xu ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Steroid Receptor ◽  
Receptor Subtype ◽  
Thyroid Function Tests ◽  
Hormone Action ◽  
Peripheral Tissues ◽  
Steroid Receptor Coactivator ◽  
Thyroid Hormone Action

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.

scholarly journals A Direct Comparison of Thyroid Hormone Receptor Protein Levels in Mice Provides Unexpected Insights into Thyroid Hormone Action

Thyroid ◽  
2020 ◽  
Vol 30 (8) ◽  
pp. 1193-1204 ◽  
Author(s):  
Svetlana Minakhina ◽  
Sanya Bansal ◽  
Alice Zhang ◽  
Michael Brotherton ◽  
Rucha Janodia ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Receptor Protein ◽  
Hormone Action ◽  
Protein Levels ◽  
Thyroid Hormone Action

Thyroid hormone (T3) rapidly activates p38 and AMPK in skeletal muscle in vivo

2008 ◽  
Vol 104 (1) ◽  
pp. 178-185 ◽  
Author(s):  
Isabella Irrcher ◽  
Donald R. Walkinshaw ◽  
Treacey E. Sheehan ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Dna Binding ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Kinase Phosphorylation ◽  
Fast Twitch

Thyroid hormone (T3) regulates the function of many tissues within the body. The effects of T3 have largely been attributed to the modulation of thyroid hormone receptor-dependent gene transcription. However, nongenomic actions of T3 via the initiation of signaling events are emerging in a number of cell types. This study investigated the ability of short-term T3 treatment to phosphorylate and, therefore, activate signaling proteins in rat tissues in vivo. The kinases investigated included p38, AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK) 1/2. Following 2 h of T3 treatment, p38 and AMPK phosphorylation was increased in both the slow-twitch soleus and the fast-twitch plantaris muscles. In contrast, ERK1/2 was not activated in either muscle type. Neither p38 nor AMPK was affected in heart. However, AMPK activation was decreased by T3 in liver. ERK1/2 activation was decreased by T3 in heart, but increased in liver. Possible downstream consequences of T3-induced kinase phosphorylation were investigated by measuring cAMP response element binding protein (CREB) and thyroid hormone receptor DNA binding, as well as peroxisome proliferator-activated receptor-α coactivator-1 mRNA levels. Protein DNA binding to the cAMP or thyroid hormone response elements was unaltered by T3. However, peroxisome proliferator-activated receptor-α coactivator-1 mRNA expression was increased following 12 h of T3 treatment in soleus. These data are the first to characterize the effects of T3 treatment on kinase phosphorylation in vivo. We show that T3 rapidly modifies kinase activity in a tissue-specific fashion. Moreover, the T3-induced phosphorylation of p38 and AMPK in both slow- and fast-twitch skeletal muscles suggests that these events may be important in mediating hormone-induced increases in mitochondrial biogenesis in skeletal muscle.

scholarly journals The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo

2008 ◽  
Vol 105 (49) ◽  
pp. 19544-19549 ◽  
Author(s):  
I. Astapova ◽  
L. J. Lee ◽  
C. Morales ◽  
S. Tauber ◽  
M. Bilban ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Action ◽  
Thyroid Hormone Action

scholarly journals In Vivo Activity of the Thyroid Hormone Receptor β- and α-Selective Agonists GC-24 and CO23 on Rat Liver, Heart, and Brain

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1136-1142 ◽  
Author(s):  
Carmen Grijota-Martínez ◽  
Eric Samarut ◽  
Thomas S. Scanlan ◽  
Beatriz Morte ◽  
Juan Bernal
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Target Genes ◽  
Thyroid Hormone Receptor ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Genetic Modifications ◽  
Hormone Analogs ◽  
Thyroid Hormone Receptor Β

Thyroid hormone analogs with selective actions through specific thyroid hormone receptor (TR) subtypes are of great interest. They might offer the possibility of mimicking physiological actions of thyroid hormone with receptor subtype or tissue specificity with therapeutic aims. They are also pharmacological tools to dissect biochemical pathways mediated by specific receptor subtypes, in a complementary way to mouse genetic modifications. In this work, we studied the in vivo activity in developing rats of two thyroid hormone agonists, the TRβ-selective GC-24 and the TRα-selective CO23. Our principal goal was to check whether these compounds were active in the rat brain. Analog activity was assessed by measuring the expression of thyroid hormone target genes in liver, heart, and brain, after administration to hypothyroid rats. GC-24 was very selective for TRβ and lacked activity on the brain. On the other hand, CO23 was active in liver, heart, and brain on genes regulated by either TRα or TRβ. This compound, previously shown to be TRα-selective in tadpoles, displayed no selectivity in the rat in vivo.

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