Differences between the effects of thyroxine and tetraiodothyroacetic acid on TSH suppression and cardiac hypertrophy

Lameloise, Nathalie; Siegrist-Kaiser, C A; O’Connell, Maureen; Burger, Albert

doi:10.1530/eje.0.1440145

Cited by 24 publications

(13 citation statements)

References 27 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tetrac has also been reported to be more effective than T 4 in suppressing TSH secretion in vivo in hypothyroid rats (Lameloise et al 2001), whereas it was less effective in inducing cardiac hypertrophy. In our study, the inhibitory effect of T 4 (around 25%) on T 3 uptake was, if anything, greater than that of Tetrac, albeit not significantly so.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, tetraiodothyroacetic acid (Tetrac) was more potent than T 4 in reducing TSH release in isolated pituitary cells (Everts et al 1995) and in hypothyroid rats (Lameloise et al 2001), but it was less efficient in inducing cardiac hypertrophy (Lameloise et al 2001). Recent work on mitochondria indicates that T 3 metabolites such as 3,5-diiodothyronine (3,5-T 2 ) may have thermogenic effects (Goglia et al 1999).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs

Verhoeven¹,

Putten²,

Hennemann³

et al. 2002

Journal of Endocrinology

View full text Add to dashboard Cite

Cellular and nuclear uptake of [125 I]tri-iodothyronine (T 3 ) and [125 I]triiodothyroacetic acid (Triac) were compared in cardiomyocytes of 2-3 day old rats, and the effect of thyroid hormone analogs on cellular T 3 uptake was measured. Cells (5-10 10 5 per well) were cultured in DMEM-M199 with 5% horse serum and 5% FCS. Incubations were performed for from 15 min to 24 h at 37 C in the same medium, 0·5% BSA and [125 I]T 3 (100 pM), or [ 125 I]Triac (240 pM). Expressed as % dose, T 3 uptake was five times Triac uptake, but expressed as fmol/pM free hormone, Triac uptake was at least 30% (P<0·001) greater than T 3 uptake, whereas the relative nuclear binding of the two tracers was comparable. The 15 min uptake of [ 125

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs

Verhoeven¹,

Putten²,

Hennemann³

et al. 2002

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Nanoparticulate tetrac cannot gain access to the cell interior and is exclusively a thyroid hormone antagonist at the integrin. This feature of exclusion is desirable, since unmodified tetrac within the cell has low-grade, but appreciable, thyromimetic activity (30).…”

Section: Translational Implications Of Nongenomic Actions Of Thyroid mentioning

confidence: 99%

“…Tetrac is an analog of T4 that inhibits binding of T4 and T3 to the TR on integrin ␣v␤3 and thus blocks the actions of agonist thyroid hormone analogs on cancer cell proliferation and on angiogenesis. 4) Covalently bonded to a nanoparticle (NP), tetrac NP acts exclusively at the cell surface thyroid hormone integrin receptor and by not entering the cell is unable to express low-grade, nucleusmediated thyromimetic activity that the unmodified molecule possesses (30). Acting at the cell surface receptor and in the absence of T4 and T3, tetrac may also affect gene expression in cancer cells (16).…”

Section: Translational Implications Of Nongenomic Actions Of Thyroid mentioning

confidence: 99%

Translational implications of nongenomic actions of thyroid hormone initiated at its integrin receptor

Davis

Davis²,

Lin³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

receptor on integrin ␣v␤3 that mediates cell surface-initiated nongenomic actions of thyroid hormone on tumor cell proliferation and on angiogenesis has been described. Transduction of the hormone signal into these recently recognized proliferative effects is by extracellular-regulated kinases 1/2 (ERK1/2). Other nongenomic actions of the hormone may be transduced by phosphatidylinositol 3-kinase (PI3K) and are initiated in cytoplasm or at the cell surface. PI3K-mediated effects are important to angiogenesis or other recently appreciated cell functions but apparently not to tumor cell division. For those actions of thyroid hormone [L-thyroxine (T4) and 3,3Ј-5-triiodo-L-thyronine (T3)] that begin at the integrin receptor, tetraiodothyroacetic acid (tetrac) is an inhibitor of and probe for the participation of the receptor in downstream intracellular events. In addition, tetrac has actions initiated at the integrin receptor that are unrelated to inhibition of the effects of T 4 and T3 but do involve gene transcription in tumor cells. Discussed here are the implications of translating these nongenomic mechanisms of thyroid hormone analogs into clinical cancer cell biology, tumor-related angiogenesis, and modulation of angiogenesis that is not related to cancer.

show abstract

“…Effect of increasing serum levels of A) T4 and tetrac (data from Lameloise et al, 2001) and B) T3 and triac (data from Liang et al, 1997) on relative heart weight (expressed as % of total body weight). jective was to develop an in vitro thyroid cell proliferation assay and explore correlations between the in vitro data obtained and in vivo data for compounds known to affect thyroid weight (OeCD, 2007).…”

Section: Fig 5: Increase In Relative Heart Weightmentioning

confidence: 99%

In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing

Jomaa

2013

ALTEX

View full text Add to dashboard Cite

Summary This study investigates the in vitro effect of eleven thyroid-active compounds known to affect pituitary and/or thyroid weights in vivo, using the proliferation of GH3 rat pituitary cells in the so-called "T-screen," and of FRTL-5 rat thyroid cells in a newly developed test denoted "TSH-screen" to gain insight into the relative value of these in vitro proliferation tests for an integrated testing strategy (ITS) for thyroid activity. Pituitary cell proliferation in the T-screen was stimulated by three out of eleven tested compounds, namely thyrotropin releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4). Of these three compounds, only T4 causes an increase in relative pituitary weight, and thus T4 was the only compound for which the effect in the in vitro assay correlated with a reported in vivo effect. As to the newly developed TSH-screen, two compounds had an effect, namely, thyroid-stimulating hormone (TSH) induced and T4 antagonized FRTL-5 cell proliferation. These effects correlated with in vivo changes induced by these compounds on thyroid weight. Altogether, the results indicate that most of the selected compounds affect pituitary and thyroid weights by modes of action different from a direct thyroid hormone receptor (THR) or TSH receptor (TSHR)-mediated effect, and point to the need for additional in vitro tests for an ITS. Additional analysis of the T-screen revealed a positive correlation between the THR-mediated effects of the tested compounds in vitro and their effects on relative heart weight in vivo, suggesting that the T-screen may directly predict this THR-mediated in vivo adverse effect.

show abstract

Differences between the effects of thyroxine and tetraiodothyroacetic acid on TSH suppression and cardiac hypertrophy

Cited by 24 publications

References 27 publications

Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs

Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs

Translational implications of nongenomic actions of thyroid hormone initiated at its integrin receptor

In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing

Contact Info

Product

Resources

About