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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both growth hormone (GH) and glucocorticoids are regulators of thyroid hormone metabolism in vertebrates. Studies on chicken embryos demonstrated that intravenous (i.v.) injection of chicken GH or glucocorticoids results in increased plasma 3,3',5-triiodothyronine (T3) concentrations, and this through a reduction of hepatic type III iodothyronine deiodinase (D3) activity. The recent cloning of chicken type I iodothyronine deiodinase (D1) and D3 offers the tools to investigate at what level (pre- or posttranslational) this downregulation of D3 occurs. Eighteen day old chicken embryos were injected with either 0.9% NaCl (control), 50 microg dexamethasone (DEX), or 20 microg cGH per animal. Plasma and tissue samples were taken 5, 10, 30, 60, 120, and 240 min post-injection. Plasma T3 and thyroxine (T4) were determined as well as in vitro hepatic D1 and D3 activities. Hepatic D1 and D3 mRNA levels were measured by both Northern analysis and competitive reverse transcription polymerase chain reaction (RT-PCR). Injection of GH or DEX resulted in a significant increase in plasma T3 when compared to controls within 30 min post-injection. This increase remained until the end of the experiment in the DEX-treated group, but not in the GH group. GH administration had no influence on plasma T4 levels, whereas DEX significantly reduced plasma T4 from 30 min onwards. Hepatic D1 activity and D1 mRNA levels showed no changes. Hepatic D3 activity, however, decreased within 10 min after DEX administration and somewhat slower after GH administration (within 30 min). Hepatic D3 activity remained low for the remainder of the experiment in the DEX-treated group, whereas D3 activity gradually returned to control levels in the GH group. This change in hepatic D3 activity was paralleled by the changes in hepatic D3 mRNA levels (r = 0.88, P = 0.0001) as confirmed by both Northern analysis and competitive RT-PCR. In conclusion, these results demonstrate that in embryonic chicken GH and DEX acutely increase plasma T3 levels by decreasing hepatic D3 activity, a decrease that seems to be regulated predominantly at the pretranslational level. These results are also an indication for the short half life (t(1/2)) of the D3 enzyme. The time lag between the effect of GH and DEX on hepatic D3 mRNA may be due to differences in the mechanism of action between both hormones, a subject that needs further investigation.
Mol Cell Endocrinol 1999 Jan 25
PMID:Acute pretranslational regulation of type III iodothyronine deiodinase by growth hormone and dexamethasone in chicken embryos. 1019 91

Compared with adults, plasma T3 concentrations in the human fetus are decreased, whereas levels of rT3 and the different iodothyronine sulfates, T4S, T3S, rT3S and 3,3'-T2S, are increased. The low T3 and high rT3 concentrations reflect the preponderance of inner ring versus outer ring deiodinase activity due to high type III iodothyronine deiodinase (D3) expression in fetal tissues, such as liver and brain, the placenta, and perhaps also the uterus, in combination with still incomplete expression of hepatic type I iodothyronine deiodinase (D1) expression. In contrast to humans, D3 is hardly expressed in the fetal rat liver. However, high D3 expression is observed in the embryonic chicken liver which decreases dramatically towards the end of incubation, resulting in a marked increase in plasma T3. Thyroid hormone is essential for the development of the brain, in which local conversion of the prohormone T4 to the active hormone T3 by the type II iodothyronine deiodinase (D2) plays a very important role. In contrast to the rat, however, little is known about the ontogeny of D2 in different human brain areas. The cause of the high concentrations of sulfated iodothyronines in fetal plasma is unknown. In adults, the liver is an important site for the clearance of these conjugates, where they are rapidly degraded by D1. Although fetal human liver expresses significant D1 activity, clearance of iodothyronine sulfates may be defective due to the lack of transporters mediating their hepatic uptake. However, production of iodothyronine sulfates may also be increased in the human fetus, although the responsible sulfotransferases and their location remain to be identified. Sulfation may be a reversible pathway of thyroid hormone inactivation, depending on the recovery of free hormone by sulfatases. However, little is known at present about the characteristics and regulation of these enzymes in fetal human tissues. Further studies are required to increase our understanding of the tissue-specific and stage-dependent regulation of thyroid hormone bioactivity during human development.
Mol Cell Endocrinol 1999 May 25
PMID:Regulation of thyroid hormone metabolism during fetal development. 1041 18

A single dose of chicken growth hormone (cGH) or dexamethasone acutely increases circulating T(3) levels in 18-day-old chicken embryos through a reduction of hepatic type III iodothyronine deiodinase (D3). The data in the present study suggest that this decrease in D3 is induced by a direct downregulation of hepatic D3 gene transcription. The lack of effect of cGH or dexamethasone on brain and kidney D3 activity, furthermore suggests that both hormones affect peripheral thyroid hormone metabolism in a tissue specific manner. Dexamethasone administration also results in an increase in brain type II iodothyronine deiodinase (D2) activity and mRNA levels that is also regulated at a transcriptional level. In contrast, however, cGH has no effect on brain D2 activity, thereby suggesting that either GH cannot pass through the blood-brain barrier in chicken or that cGH and dexamethasone regulate thyroid hormone deiodination by different mechanisms. In addition, the very short half-life of D2 and D3 (t(1/2)<1 h) in comparison with the longer half life of type I iodothyronine deiodinase (D1, t(1/2)>8 h), allows for D2 and D3 to play a more prominent role in the acute regulation of peripheral thyroid hormone metabolism than D1.
Mol Cell Endocrinol 2001 Oct 25
PMID:Transcriptional regulation of iodothyronine deiodinases during embryonic development. 1160 18

Genomic imprinting is a phenomenon that causes parent-origin-specific monoallelic expression of a small subset of genes, known as imprinted genes, by parentally inherited epigenetic marks. Imprinted genes at the delta-like homolog 1 gene (Dlk1)-type III iodothyronine deiodinase gene (Dio3) imprinted domain, regulated by intergenic differentially methylated region (IG-DMR), are essential for normal development of late embryonic stages. Although the functions of IG-DMR have been reported by generating knockout mice, molecular details of the regulatory mechanisms are not fully understood as the specific sequence(s) of IG-DMR have not been identified. Here, we generated mutant mice by deleting a 216 bp tandem repeated sequence in IG-DMR, which comprised seven repeats of 24 bp motifs, by genome editing technologies. The mutant mice showed that paternal transmission of the deletion allele, but not maternal transmission, induces severe growth retardation and perinatal lethality, possibly due to placental defects. Embryos with a paternally transmitted deletion allele showed biallelic expression of maternally expressed genes and repression of paternally expressed genes. DNA methylation status also showed loss of methylation at IG-DMR and Gtl2-DMR, indicating that the tandem repeat sequence of IG-DMR is one of the functional sequences of IG-DMR, which is required for maintaining DNA methylation imprints of paternal allele at IG-DMR.
Hum Mol Genet 2018 09 15
PMID:A tandem repeat array in IG-DMR is essential for imprinting of paternal allele at the Dlk1-Dio3 domain during embryonic development. 2993 Nov 70

Neural stem cells are fundamental to development of the central nervous system (CNS)-as well as its plasticity and regeneration-and represent a potential tool for neuro transplantation therapy and research. This study is focused on examination of the proliferation dynamic and fate of embryonic neural stem cells (eNSCs) under differentiating conditions. In this work, we analyzed eNSCs differentiating alone and in the presence of sonic hedgehog (SHH) or triiodothyronine (T3) which play an important role in the development of the CNS. We found that inhibition of the SHH pathway and activation of the T3 pathway increased cellular health and survival of differentiating eNSCs. In addition, T3 was able to increase the expression of the gene for the receptor smoothened (Smo), which is part of the SHH signaling cascade, while SHH increased the expression of the T3 receptor beta gene (Thrb). This might be the reason why the combination of SHH and T3 increased the expression of the thyroxine 5-deiodinase type III gene (Dio3), which inhibits T3 activity, which in turn affects cellular health and proliferation activity of eNSCs.
Int J Mol Sci 2020 May 23
PMID:Sonic Hedgehog and Triiodothyronine Pathway Interact in Mouse Embryonic Neural Stem Cells. 3245 61