Ontogenic Redistribution of Type 2 Deiodinase Messenger Ribonucleic Acid in the Brain of Chicken

Gereben, Balázs; Pachucki, Janusz; Kollár, Anna; Liposits, Zsolt; Fekete, Csaba

doi:10.1210/en.2004-0229

Cited by 35 publications

(16 citation statements)

References 42 publications

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“…In situ hybridization of the chicken choroid plexus using a D2 cRNA probe clearly showed the expression of D2 mRNA in the epithelial cells. Furthermore, D2 mRNA was demonstrated in elongated cell clusters throughout the brain, comparable with the results recently described by Gereben et al (2004). Comparison of the D2 protein distribution with that of D1 and D3 protein within the choroid plexus using earlier developed antisera (Verhoelst et al 2002(Verhoelst et al , 2003, led to the conclusion that neither of the two other deiodinase proteins are present in the choroid plexus.…”

Section: Discussionsupporting

confidence: 85%

Type II iodothyronine deiodinase protein in chicken choroid plexus: additional perspectives on T3 supply in the avian brain

Verhoelst¹,

Darras²,

Roelens³

et al. 2004

Journal of Endocrinology

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It is widely accepted that type II iodothyronine deiodinase (D2) is mostly present in the brain, where it maintains the homeostasis of thyroid hormone (TH) levels. Although intensive studies have been performed on activity and mRNA levels of the deiodinases, very little is known about their expression at the protein level due to the lack of specific antisera. The current study reports the production of a specific D2 polyclonal antiserum and its use in the comparison of D2 protein distribution with that of type I (D1) and type III (D3) deiodinase protein in the choroid plexus at the blood-brain barrier level. Immunocytochemistry showed very high D2 protein expression in the choroid plexus, especially in the epithelial cells, whereas the D1 and D3 proteins were absent. Furthermore, dexamethasone treatment led to an up-regulation of the D2 protein in the choroid plexus. The expression of D2 protein in the choroid plexus led to a novel insight into the working mechanism of the uptake and transport of thyroid hormones along the blood-brain barrier in birds. It is hypothesized that D2 allows the prohormone thyroxine (T 4 ) to be converted into the active 3,5,3 -triiodothyronine (T 3 ). Within the choroidal epithelial cells. T 3 is subsequently bound to its carrier protein, transthyretin (TTR), to allow transport through the cerebrospinal fluid. Neurons can thus not only be provided with a sufficient T 3 level via the aid of the astrocytes, as was hypothesized previously based on in situ hybridization data, but also by means of T 4 deiodination by D2, directly at the blood-brain barrier level.

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Section: Discussionsupporting

confidence: 85%

Type II iodothyronine deiodinase protein in chicken choroid plexus: additional perspectives on T3 supply in the avian brain

Verhoelst¹,

Darras²,

Roelens³

et al. 2004

Journal of Endocrinology

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“…Hybridization is also present overlying a cell-clear zone above the tuberoinfundibular sulci, and in the substance of the median eminence and pituitary stalk where it extends into the external zone adjacent to the portal capillaries. A similar distribution of D2 or D2 mRNA has been identified in the mouse (personal observations), chicken (39) and human hypothalamus (32) (Fig. 3).…”

Section: Anatomic Distribution Of Deiodinase In the Hypothalamussupporting

confidence: 82%

Role of Thyroid Hormone Deiodination in the Hypothalamus

Lechan

Fekete

2005

Thyroid

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Iodothyronine deiodinases (D1, D2, and D3) comprise a family of selenoproteins that are involved in the conversion of thyroxine (T(4)) to active triiodothyronine (T(3)), and also the inactivation of both thyroid hormones. The deiodinase enzymes are of critical importance for the normal development and function of the central nervous system. D1 is absent from the human brain, suggesting that D2 and D3 are the two main enzymes involved in the maintenance of thyroid hormone homeostasis in the central nervous system, D2 as the primary T(3)-producing enzyme, and D3 as the primary inactivating enzyme. While the coordinated action of D2 and D3 maintain constant T(3) levels in the cortex independently from the circulating thyroid hormone levels, the role of deiodinases in the hypothalamus may be more complex, as suggested by the regulation of D2 activity in the hypothalamus by infection, fasting and changes in photoperiod. Tanycytes, the primary source of D2 activity in the hypothalamus, integrate hormonal and probably neuronal signals, and under specific conditions, may influence neuroendocrine functions by altering local T(3) tissue concentrations. This function may be of particular importance in the regulation of the hypothalamic-pituitary-thyroid axis during fasting and infection, and in the regulation of appetite and reproductive function. Transient expression of D3 in the preoptic region during a critical time of development suggests a special role for this deiodinase in sexual differentiation of the brain.

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“…For the in situ testing, livers from P1 euthyroid and adult hypothyroid mice were quickly frozen in dry ice and then stored at −80°C. The samples were processed as described previously (31), with modifications as detailed in SI Appendix.…”

Section: Methodsmentioning

confidence: 99%

Perinatal deiodinase 2 expression in hepatocytes defines epigenetic susceptibility to liver steatosis and obesity

Fonseca

Fernandes

McAninch

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Thyroid hormone binds to nuclear receptors and regulates gene transcription. Here we report that in mice, at around the first day of life, there is a transient surge in hepatocyte type 2 deiodinase (D2) that activates the prohormone thyroxine to the active hormone triiodothyronine, modifying the expression of ∼165 genes involved in broad aspects of hepatocyte function, including lipid metabolism. Hepatocyte-specific D2 inactivation (ALB-D2KO) is followed by a delay in neonatal expression of key lipid-related genes and a persistent reduction in peroxisome proliferator-activated receptor-γ expression. Notably, the absence of a neonatal D2 peak significantly modifies the baseline and long-term hepatic transcriptional response to a high-fat diet (HFD). Overall, changes in the expression of approximately 400 genes represent the HFD response in control animals toward the synthesis of fatty acids and triglycerides, whereas in ALB-D2KO animals, the response is limited to a very different set of only approximately 200 genes associated with reverse cholesterol transport and lipase activity. A whole genome methylation profile coupled to multiple analytical platforms indicate that 10-20% of these differences can be related to the presence of differentially methylated local regions mapped to sites of active/suppressed chromatin, thus qualifying as epigenetic modifications occurring as a result of neonatal D2 inactivation. The resulting phenotype of the adult ALB-D2KO mouse is dramatic, with greatly reduced susceptibility to diet-induced steatosis, hypertriglyceridemia, and obesity.deiodinase | thyroid hormone | lipids | steatosis | obesity

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Ontogenic Redistribution of Type 2 Deiodinase Messenger Ribonucleic Acid in the Brain of Chicken

Cited by 35 publications

References 42 publications

Type II iodothyronine deiodinase protein in chicken choroid plexus: additional perspectives on T3 supply in the avian brain

Type II iodothyronine deiodinase protein in chicken choroid plexus: additional perspectives on T3 supply in the avian brain

Role of Thyroid Hormone Deiodination in the Hypothalamus

Perinatal deiodinase 2 expression in hepatocytes defines epigenetic susceptibility to liver steatosis and obesity

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