scholarly journals Life Without Thyroid Hormone Receptor

Endocrinology ◽  
2021 ◽  
Vol 162 (4) ◽  
Author(s):  
Yun-Bo Shi
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Developmental Process ◽  
Gene Knockout ◽  
Postembryonic Development ◽  
Vertebrate Development ◽  
Animal Development ◽  
Necessary And Sufficient ◽  
Inducible Genes ◽  
T3 Receptors

Abstract Thyroid hormone (T3) is critical not only for organ function and metabolism in the adult but also for animal development. This is particularly true during the neonatal period when T3 levels are high in mammals. Many processes during this postembryonic developmental period resemble those during amphibian metamorphosis. Anuran metamorphosis is perhaps the most dramatic developmental process controlled by T3 and affects essentially all organs/tissues, often in an organ autonomous manner. This offers a unique opportunity to study how T3 regulates vertebrate development. Earlier transgenic studies in the pseudo-tetraploid anuran Xenopus laevis revealed that T3 receptors (TRs) are necessary and sufficient for mediating the effects of T3 during metamorphosis. Recent gene knockout studies with gene-editing technologies in the highly related diploid anuran Xenopus tropicalis showed, surprisingly, that TRs are not required for most metamorphic transformations, although tadpoles lacking TRs are stalled at the climax of metamorphosis and eventually die. Analyses of the changes in different organs suggest that removal of TRs enables premature development of many adult tissues, likely due to de-repression of T3-inducible genes, while preventing the degeneration of tadpole-specific tissues, which is possibly responsible for the eventual lethality. Comparison with findings in TR knockout mice suggests both conservation and divergence in TR functions, with the latter likely due to the greatly reduced need, if any, to remove embryo/prenatal-specific tissues during mammalian postembryonic development.

scholarly journals Transgenic Analysis Reveals that Thyroid Hormone Receptor Is Sufficient To Mediate the Thyroid Hormone Signal in Frog Metamorphosis

2004 ◽  
Vol 24 (20) ◽  
pp. 9026-9037 ◽  
Author(s):  
Daniel R. Buchholz ◽  
Akihiro Tomita ◽  
Liezhen Fu ◽  
Bindu D. Paul ◽  
Yun-Bo Shi
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Target Genes ◽  
Thyroid Hormone Receptor ◽  
Gene Activation ◽  
Inducible Promoter ◽  
Vertebrate Development ◽  
Transcription System

ABSTRACT Thyroid hormone (T3) has long been known to be important for vertebrate development and adult organ function. Whereas thyroid hormone receptor (TR) knockout and transgenic studies of mice have implicated TR involvement in mammalian development, the underlying molecular bases for the resulting phenotypes remain to be determined in vivo, especially considering that T3 is known to have both genomic, i.e., through TRs, and nongenomic effects on cells. Amphibian metamorphosis is an excellent model for studying the role of TR in vertebrate development because of its total dependence on T3. Here we investigated the role of TR in metamorphosis by developing a dominant positive mutant thyroid hormone receptor (dpTR). In the frog oocyte transcription system, dpTR bound a T3-responsive promoter and activated the promoter independently of T3. Transgenic expression of dpTR under the control of a heat shock-inducible promoter in premetamorphic tadpoles led to precocious metamorphic transformations. Molecular analyses showed that dpTR induced metamorphosis by specifically binding to known T3 target genes, leading to increased local histone acetylation and gene activation, similar to T3-bound TR during natural metamorphosis. Our experiments indicated that the metamorphic role of T3 is through genomic action of the hormone, at least on the developmental parameters tested. They further provide the first example where TR is shown to mediate directly and sufficiently these developmental effects of T3 in individual organs by regulating target gene expression in these organs.

scholarly journals Effects of hyper- and hypothyroid on expression of thyroid hormone receptor mRNA in rat myocardium

2007 ◽  
Vol 195 (3) ◽  
pp. 429-438 ◽  
Author(s):  
C R Liu ◽  
L Y Li ◽  
F Shi ◽  
X Y Zang ◽  
Y M Liu ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Developmental Process ◽  
Control Group ◽  
Rat Myocardium ◽  
Receptor Mrna ◽  
Close Relationship ◽  
Heart Lesions

Thyroid dysfunction is classified into hyperthyroidism and congenital hypothyroidism (CH). Both hyperthyroidism and CH can cause heart lesions; however, the mechanisms involved remain unclear. The left ventricle was collected from eu-, hyper-, and hypothyroid rat. RNA was extracted and reverse-transcripted to cDNA. Real-time fluorescence quantitation-PCR was used to quantify the differential expression of thyroid hormone receptor (TR) subtype mRNA among eu-, hyper-, and hypothyroid rat myocardium. Here, we show that compared with the normal myocardium, TRα1 mRNA expression was upregulated by 51% (P<0.01), TRα2 mRNA expression was downregulated by 58% (P<0.01), and TRβ1 mRNA expression remained unchanged in hyperthyroid rat myocardium (P>0.05). TRα1, TRα2, and TRβ1 were expressed in normal and hypothyroid rat myocardium throughout the developmental process. In hypothyroid rats, myocardial TRα1 mRNA expression was generally downregulated and the expression peak appeared late. Myocardial TRα2 mRNA expression was generally upregulated and the expression peak appeared late. Myocardial TRβ1 mRNA expression was generally downregulated and changed similarly with the control group. In addition, the hypogenetic myocardium can be seen in the hypothyroid rat by pathology study. Taken together, the abnormal expression of TR subtype mRNA may have a close relationship with the pathogenesis of CH and hyperthyroidism heart disease.

scholarly journals Direct Activation of Xenopus Iodotyrosine Deiodinase by Thyroid Hormone Receptor in the Remodeling Intestine during Amphibian Metamorphosis

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 5082-5089 ◽  
Author(s):  
Kenta Fujimoto ◽  
Kazuo Matsuura ◽  
Biswajit Das ◽  
Liezhen Fu ◽  
Yun-Bo Shi
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Promoter Region ◽  
Thyroid Hormone Receptor ◽  
Postembryonic Development ◽  
The Other ◽  
Iodotyrosine Deiodinase ◽  
Developmental Role ◽  
Intestinal Remodeling

Abstract Thyroid hormone (TH) plays critical roles during vertebrate postembryonic development. TH production in the thyroid involves incorporating inorganic iodide into thyroglobulin. The expression of iodotyrosine deiodinase (IYD; also known as iodotyrosine dehalogenase 1) in the thyroid gland ensures efficient recycling of iodine from the byproducts of TH biosynthesis: 3′-monoiodotyrosine and 3′, 5′-diiodotyrosine. Interestingly, IYD is known to be expressed in other organs in adult mammals, suggesting iodine recycling outside the thyroid. On the other hand, the developmental role of iodine recycling has yet to be investigated. Here, using intestinal metamorphosis as a model, we discovered that the Xenopus tropicalis IYD gene is strongly up-regulated by TH during metamorphosis in the intestine but not the tail. We further demonstrated that this induction was one of the earliest events during intestinal metamorphosis, with IYD being activated directly through the binding of liganded TH receptors to a TH response element in the IYD promoter region. Because iodide is mainly taken up from the diet in the intestine and the tadpole stops feeding during metamorphosis when the intestine is being remodeled, our findings suggest that IYD transcription is activated by liganded TH receptors early during intestinal remodeling to ensure efficient iodine recycling at the climax of metamorphosis when highest levels of TH are needed for the proper transformations of different organs.

scholarly journals Recruitment of N-CoR/SMRT-TBLR1 Corepressor Complex by Unliganded Thyroid Hormone Receptor for Gene Repression during Frog Development

2004 ◽  
Vol 24 (8) ◽  
pp. 3337-3346 ◽  
Author(s):  
Akihiro Tomita ◽  
Daniel R. Buchholz ◽  
Yun-Bo Shi
Keyword(s):  
Thyroid Hormone ◽  
Transcriptional Repression ◽  
Histone Deacetylases ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Histone Deacetylation ◽  
Gene Repression ◽  
Vertebrate Development ◽  
Inducible Promoters

ABSTRACT The corepressors N-CoR (nuclear receptor corepressor) and SMRT (silencing mediator for retinoid and thyroid hormone receptors) interact with unliganded nuclear hormone receptors, including thyroid hormone (T3) receptor (TR). Several N-CoR/SMRT complexes containing histone deacetylases have been purified. The best studied among them are N-CoR/SMRT complexes containing TBL1 (transducin beta-like protein 1) or TBLR1 (TBL1-related protein). Despite extensive studies of these complexes, there has been no direct in vivo evidence for the interaction of TBL1 or TBLR1 with TR or the possible involvement of such complexes in gene repression by any nuclear receptors in any animals. Here, we used the frog oocyte system to demonstrate that unliganded TR interacts with TBLR1 and recruits TBLR1 to its chromatinized target promoter in vivo, accompanied by histone deacetylation and gene repression. We further provide evidence to show that the recruitment of TBLR1 or related proteins is important for repression by unliganded TR. To investigate the potential role for TBLR1 complexes during vertebrate development, we made use of T3-dependent amphibian metamorphosis as a model. We found that TBLR1, SMRT, and N-CoR are recruited to T3-inducible promoters in premetamorphic tadpoles and are released upon T3 treatment, which induces metamorphosis. More importantly, we demonstrate that the dissociation of N-CoR/SMRT-TBLR1 complexes from endogenous TR target promoters is correlated with the activation of these genes during spontaneous metamorphosis. Taken together, our studies provide in vivo evidence for targeted recruitment of N-CoR/SMRT-TBLR1 complexes by unliganded TR in transcriptional repression during vertebrate development.

scholarly journals A role of unliganded thyroid hormone receptor in postembryonic development in Xenopus laevis

2007 ◽  
Vol 124 (6) ◽  
pp. 476-488 ◽  
Author(s):  
Yukiyasu Sato ◽  
Daniel R. Buchholz ◽  
Bindu D. Paul ◽  
Yun-Bo Shi
Keyword(s):  
Thyroid Hormone ◽  
Xenopus Laevis ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Postembryonic Development

scholarly journals Thyroid Hormone Receptor-α Gene Knockout Mice Are Protected from Diet-Induced Hepatic Insulin Resistance

Endocrinology ◽  
2012 ◽  
Vol 153 (2) ◽  
pp. 583-591 ◽  
Author(s):  
François R. Jornayvaz ◽  
Hui-Young Lee ◽  
Michael J. Jurczak ◽  
Tiago C. Alves ◽  
Fitsum Guebre-Egziabher ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Thyroid Hormone ◽  
Knockout Mice ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Gene Knockout ◽  
Hepatic Insulin Resistance ◽  
Gene Knockout Mice ◽  
Thyroid Hormone Receptor Α

scholarly journals Thyroid hormone regulates abrupt skin morphogenesis during zebrafish postembryonic development

2021 ◽  
Author(s):  
Andrew J Aman ◽  
Lauren M Saunders ◽  
Margaret Kim ◽  
David M Parichy
Keyword(s):  
Thyroid Hormone ◽  
Molecular Mechanisms ◽  
Hormone Receptors ◽  
Postembryonic Development ◽  
Hair Follicles ◽  
Vertebrate Development ◽  
Skin Development ◽  
Ordered Array ◽  
Skin Morphogenesis

Thyroid hormone is a key regulator of post-embryonic vertebrate development. Skin is a biomedically important thyroid hormone target organ, but the cellular and molecular mechanisms underlying skin pathologies associated with thyroid dysfunction remain obscure. The transparent skin of zebrafish is an accessible model system for studying vertebrate skin development. During post-embryonic development of the zebrafish, scales emerge in the skin from a hexagonally patterned array of dermal papillae, like other vertebrate skin appendages such as feathers and hair follicles. We show here that thyroid hormone regulates the rate of post-embryonic dermal development through interaction with nuclear hormone receptors. This couples skin development with body growth to generate a well ordered array of correctly proportioned scales. This work extends our knowledge of thyroid hormone actions on skin by providing in-vivo evidence that thyroid hormone regulates multiple aspects of dermal development.

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