Dysregulation of iodothyronine deiodinase enzyme expression and function in human pituitary tumours

Tannahill, Lesley; Visser, Theo J.; McCabe, Christopher; Kachilele, Stivelia; Boelaert, Kristien; Sheppard, M. C.; Franklyn, Jayne A.; Gittoes, Neil

doi:10.1046/j.1365-2265.2002.01541.x

Cited by 51 publications

(26 citation statements)

References 44 publications

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“…Although a wide variation on D1 activity among the tumor histological subtypes has been reported, the highest activities were seen in the thyrotroph and lactotroph adenomas. Approximately, half of these tumors presented D1 activities several-fold greater than any of the normal pituitary samples (Baur et al 2002, Tannahill et al 2002.…”

Section: Human Neoplasiasmentioning

confidence: 99%

Type 1 iodothyronine deiodinase in human physiology and disease

Maia

Goemann²,

Meyer³

et al. 2011

Journal of Endocrinology

194

123

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Thyroid hormone is essential for the normal function of virtually all tissues. The iodothyronine deiodinases catalyze the removal of an iodine residue from the pro-hormone thyroxine (T 4 ) molecule, thus producing either the active form triiodothyronine (T 3 ; activation) or inactive metabolites (reverse T 3 ; inactivation). Type I deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on normal thyroid hormone metabolism and pathological processes. Although peripheral D1-generated T 3 production contributes to a portion of plasma T 3 in euthyroid state, pathologically increased thyroidal D1 activity seems to be the main cause of the elevated T 3 concentrations observed in hyperthyroid patients. On the other hand, D1-deficient mouse models show that, in the absence of D1, inactive and lesser iodothyronines are excreted in feces with the loss of associated iodine, demonstrating the scavenging function for D1 that might be particularly important in an iodine deficiency setting. Polymorphisms in the DIO1 gene have been associated with changes in serum thyroid hormone levels, whereas decreased D1 activity has been reported in the nonthyroid illness syndrome and in several human neoplasias. The current review aims at presenting an updated picture of the recent advances made in the biochemical and molecular properties of D1 as well as its role in human physiology.

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Section: Human Neoplasiasmentioning

confidence: 99%

Type 1 iodothyronine deiodinase in human physiology and disease

Maia

Goemann²,

Meyer³

et al. 2011

Journal of Endocrinology

194

123

View full text Add to dashboard Cite

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“…We have recently described the presence of both D2 and D3 activity in the human anterior pituitary (4). Type I deiodinase activity does not appear to play a major role in thyroid hormone feedback in the human anterior pituitary (3). T 3 acts by binding to thyroid hormone receptor (TR) isoforms, which have been reported in both human and rat anterior pituitary (5,6).…”

Section: Introductionmentioning

confidence: 99%

Novel neuroanatomical pathways for thyroid hormone action in the human anterior pituitary

Alkemade¹,

Friesema²,

Kuiper³

et al. 2006

eur j endocrinol

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Objective: An increasing number of proteins appear to be involved in thyroid hormone feedback action at the level of the anterior pituitary, but the cell types expressing these proteins are largely unknown. The aim of the present study was to identify cell types in the human anterior pituitary that express type II and type III deiodinase (D2 and D3), the recently described thyroid hormone transporter (MCT8) and thyroid hormone receptor (TR) isoforms by means of double-labeling immunocytochemistry. Results: We found TR isoforms to be expressed most prominently in gonadotropes and -although to a lesser extent -in thyrotropes, corticotropes, lactotropes and somatotropes. D3 staining showed a distribution pattern that was remarkably similar. By contrast, D2 immunoreactivity was observed exclusively in folliculostellate (FS) cells showing coexpression with human leukocyte antigen (HLA), a marker of major histocompatibility complex (MHC)-class II. MCT8 immunostaining was present in FS cells without HLA coexpression. Conclusions: From these results, we propose a novel neuroanatomical model for thyroid hormone feedback on the human pituitary, with a central role for FS cells in thyroid hormone activation, which thus play an important role in the suppression of TSH secretion by circulating thyroxine (T 4 ).European Journal of Endocrinology 154 491-500

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“…Adenohypophyseal T3 production by D2 plays an important role in feedback regulation of TSH secretion by thyroid hormones and also regulates pituitary cell growth and differentiation (Barrera-Hernandez et al, 1999;Schneider et al, 2001;Stahl et al, 1999). Interestingly, a variable expression of D2 has been described in a number of subtypes of pituitary adenomas, implying that this enzyme is still active in tumor tissues (Baur et al, 2002;Tannahill et al, 2002). It is well established that thyroid hormones play an important role at multiple steps in the development of glial cells that, like C-cells, is of neuroectodermic origin (Rodríguez-Peña et al, 1999) and high levels of D2 activity was noted in oligodendrogliomas, a tumor derived from the glial cells (Mori et al, 1993;Murakami et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Type 2 iodothyronine deiodinase is highly expressed in medullary thyroid carcinoma

Meyer

Goemann

Dora

et al. 2008

Molecular and Cellular Endocrinology

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SummaryType II deiodinase (D2) plays a critical role in controlling intracellular T3 concentration and early studies indicated a follicular but not a parafollicular C-cell origin of D2 activity in the thyroid gland. Here, we show that D2 is highly expressed in human medullary thyroid carcinoma (MTC), a tumour that arises from the C-cells. D2 transcripts were detected in all MTC samples obtained from 12 unselected MTC patients and the levels of D2 activity were comparable to those found in surrounding normal follicular tissue (0.41±0.10 vs 0.43±0.41 fmol.min.mg.protein, P=0.91). Additional analysis in the TT cells, a human MTC cell line, demonstrated that the D2 expression is down regulated by thyroid hormones and enhanced by cAMP analogs and dexamethasone. The thyroid hormone receptor α1 and β isoforms were also detected in all MTC samples and in TT cells, thus suggesting a potential role of T3 locally produced by D2 in this neoplastic tissue.

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Dysregulation of iodothyronine deiodinase enzyme expression and function in human pituitary tumours

Cited by 51 publications

References 44 publications

Type 1 iodothyronine deiodinase in human physiology and disease

Type 1 iodothyronine deiodinase in human physiology and disease

Novel neuroanatomical pathways for thyroid hormone action in the human anterior pituitary

Type 2 iodothyronine deiodinase is highly expressed in medullary thyroid carcinoma

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