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 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 Unliganded Thyroid Hormone Receptor α Controls Developmental Timing in Xenopus tropicalis

Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 721-734 ◽  
Author(s):  
Luan Wen ◽  
Yun-Bo Shi
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Postembryonic Development ◽  
Xenopus Tropicalis ◽  
The Other ◽  
Growth Hormone Gene ◽  
Regulate Gene Expression ◽  
Other Hand ◽  
Regulate Gene

Thyroid hormone (T3) affects adult metabolism and postembryonic development in vertebrates. T3 functions mainly via binding to its receptors (TRs) to regulate gene expression. There are 2 TR genes, TRα and TRβ, with TRα more ubiquitously expressed. During development, TRα expression appears earlier than T3 synthesis and secretion into the plasma. This and the ability of TRs to regulate gene expression both in the presence and absence of T3 have indicated a role for unliganded TR during vertebrate development. On the other hand, it has been difficult to study the role of unliganded TR during development in mammals because of the difficulty to manipulate the uterus-enclosed, late-stage embryos. Here we use amphibian development as a model to address this question. We have designed transcriptional activator–like effector nucleases (TALENs) to mutate the TRα gene in Xenopus tropicalis. We show that knockdown of TRα enhances tadpole growth in premetamorphic tadpoles, in part because of increased growth hormone gene expression. More importantly, the knockdown also accelerates animal development, with the knockdown animals initiating metamorphosis at a younger age and with a smaller body size. On the other hand, such tadpoles are resistant to exogenous T3 treatment and have delayed natural metamorphosis. Thus, our studies not only have directly demonstrated a critical role of endogenous TRα in mediating the metamorphic effect of T3 but also revealed novel functions of unliganded TRα during postembryonic development, that is, regulating both tadpole growth rate and the timing of metamorphosis.

scholarly journals The thyroid hormone receptor gene (c-erbA alpha) is expressed in advance of thyroid gland maturation during the early embryonic development of Xenopus laevis.

1991 ◽  
Vol 11 (10) ◽  
pp. 5079-5089 ◽  
Author(s):  
D E Banker ◽  
J Bigler ◽  
R N Eisenman
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Xenopus Laevis ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Thyroid Hormone Receptors ◽  
Stages Of Development ◽  
Xenopus Development

The c-erbA proto-oncogene encodes the thyroid hormone receptor, a ligand-dependent transcription factor which plays an important role in vertebrate growth and development. To define the role of the thyroid hormone receptor in developmental processes, we have begun studying c-erbA gene expression during the ontogeny of Xenopus laevis, an organism in which thyroid hormone has well-documented effects on morphogenesis. Using polymerase chain reactions (PCR) as a sensitive assay of specific gene expression, we found that polyadenylated erbA alpha RNA is present in Xenopus cells at early developmental stages, including the fertilized egg, blastula, gastrula, and neurula. By performing erbA alpha-specific PCR on reverse-transcribed RNAs from high-density sucrose gradient fractions prepared from early-stage embryos, we have demonstrated that these erbA transcripts are recruited to polysomes. Therefore, erbA is expressed in Xenopus development prior to the appearance of the thyroid gland anlage in tailbud-stage embryos. This implies that erbA alpha/thyroid hormone receptors may play ligand-independent roles during the early development of X. laevis. Quantitative PCR revealed a greater than 25-fold range in the steady-state levels of polyadenylated erbA alpha RNA across early stages of development, as expressed relative to equimolar amounts of total embryonic RNA. Substantial increases in the levels of erbA alpha RNA were noted at stages well after the onset of zygotic transcription at the mid-blastula transition, with accumulation of erbA alpha transcripts reaching a relative maximum in advance of metamorphosis. We also show that erbA alpha RNAs are expressed unequally across Xenopus neural tube embryos. This differential expression continues through later stages of development, including metamorphosis. This finding suggests that erbA alpha/thyroid hormone receptors may play roles in tissue-specific processes across all of Xenopus 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 Potential role of two novel agonists of thyroid hormone receptor‐β on liver regeneration

2020 ◽  
Vol 53 (5) ◽  
Author(s):  
Andrea Perra ◽  
Marta Anna Kowalik ◽  
Lavinia Cabras ◽  
Massimiliano Runfola ◽  
Simona Sestito ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Liver Regeneration ◽  
Hormone Receptor ◽  
Potential Role ◽  
Thyroid Hormone Receptor ◽  
Thyroid Hormone Receptor Β

scholarly journals Thyroid hormone receptor-β1 signaling is critically involved in regulating secondary ossification via promoting transcription of the Ihh gene in the epiphysis

2016 ◽  
Vol 310 (10) ◽  
pp. E846-E854 ◽  
Author(s):  
Weirong Xing ◽  
Patrick Aghajanian ◽  
Helen Goodluck ◽  
Chandrasekhar Kesavan ◽  
Shaohong Cheng ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Proximal Tibia ◽  
Thyroid Hormone Receptor ◽  
Bone Development ◽  
Day Treatment ◽  
Mrna Level ◽  
Ossification Center ◽  
Mobility Shift ◽  
Distal Promoter

Thyroid hormone (TH) action is mediated through two nuclear TH receptors, THRα and THRβ. Although the role of THRα is well established in bone, less is known about the relevance of THRβ-mediated signaling in bone development. On ther basis of our recent finding that TH signaling is essential for initiation and formation of secondary ossification center, we evaluated the role of THRs in mediating TH effects on epiphysial bone formation. Two-day treatment of TH-deficient Tshr −/− mice with TH increased THRβ1 mRNA level 3.4-fold at day 7 but had no effect on THRα1 mRNA level at the proximal tibia epiphysis. Treatment of serum-free cultures of tibias from 3-day-old mice with T3 increased THRβ1 expression 2.1- and 13-fold, respectively, at 24 and 72 h. Ten-day treatment of Tshr −/− newborns ( days 5–14) with THRβ1 agonist GC1 at 0.2 or 2.0 μg/day increased BV/TV at day 21 by 225 and 263%, respectively, compared with vehicle treatment. Two-day treatment with GC1 (0.2 μg/day) increased expression levels of Indian hedgehog ( Ihh) 100-fold, osterix 15-fold, and osteocalcin 59-fold compared with vehicle at day 7 in the proximal tibia epiphysis. Gel mobility shift assay demonstrated that a putative TH response element in the distal promoter of mouse Ihh gene interacted with THRβ1. GC1 treatment (1 nM) increased Ihh distal promoter activity 20-fold after 48 h in chondroctyes. Our data suggest a novel role for THRβ1 in secondary ossification at the epiphysis that involves transcriptional upregulation of Ihh gene.

scholarly journals Ligand-dependent enhancement of human antithrombin gene expression by retinoid X receptor α and thyroid hormone receptor β

1996 ◽  
Vol 318 (1) ◽  
pp. 263-270 ◽  
Author(s):  
René W. L. M. NIESSEN ◽  
Farhad REZAEE ◽  
Pieter H. REITSMA ◽  
Marjolein PETERS ◽  
Jan J. M. de VIJLDER ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Promoter Region ◽  
Promoter Activity ◽  
Thyroid Hormone Receptor ◽  
Retinoid X Receptor ◽  
Hepatoma Cell Line ◽  
Promoter Fragment ◽  
Thyroid Hormone Receptor Β

We studied potential modulators of antithrombin gene expression. A putative hormone response element (HRE) was identified by sequence similarity analysis of the antithrombin promoter, situated between nucleotides -92 and -54 relative to the transcription start site. This HRE contains three hexanucleotide motifs with an AGGTCA consensus, which are potential targets of members of the steroid/thyroid superfamily of nuclear receptors. Stimulation of the hepatoma cell line HepG2 with the receptor ligands l-3,5,3´-tri-iodothyronine, all-trans retinoic acid, or their combination, increased production of antithrombin into the culture medium by 1.3-, 1.6-, and 2.0-fold, respectively. In contrast, the receptor ligand 1,25-dihydroxycholecalciferol [1,25-(OH)2VitD3] did not influence antithrombin production. Analysis of promoter chloramphenicol acetyltransferase (CAT) constructs, showed that the first 86 bp of the antithrombin promoter region are sufficient for basal transcription. The DNA length polymorphism of 32 bp or 108 bp, located upstream of position -276, did not influence antithrombin promoter activity. The antithrombin promoter activity dropped to background values when deleting the region -97/-49 of promoter fragment -453/+57. Transactivation of the antithrombin promoter by retinoid X receptor α (RXRα) (5–7-fold) or thyroid hormone receptor β (TRβ) (4–5-fold) was only observed when at least -167/+57 bp of the promoter region is present in CAT constructs, and when the appropriate ligand of the nuclear receptor was added. This transactivation was not observed upon deletion of the antithrombin promoter region -97/-49. With three copies of the antithrombin promoter fragment -109/-42 in front of the thymidine kinase minimal promoter, transactivation was only obtained with RXRα, and not with TRβ. In conclusion, these results indicate that the ligand-dependent enhancement of antithrombin gene expression is regulated by RXRα as well as by TRβ. Transactivation of antithrombin gene expression by RXRα and TRβ appears to be dependent upon the presence of promoter region up to nucleotide -167. The HRE segment (-109/-42) only confers RXRα responsiveness to a heterologous promoter. Further study is needed to unravel the exact nature of this HRE and its 5´-flanking sequences.

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