Event:1116

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Event Title

Triiodothyronine (T3) in tissues, Decreased

Key Event Overview

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AOPs Including This Key Event

AOP Name Event Type Essentiality
Thyroperoxidase inhibition leading to altered amphibian metamorphosis KE Moderate
Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis KE Moderate
Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis KE Moderate
Type I iodothyronine deiodinase (DIO1) inhibition leading to altered amphibian metamorphosis KE Strong
Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis KE Strong
Pendrin inhibition leading to altered amphibian metamorphosis KE Moderate
Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis KE Moderate
Hepatic nuclear receptor activation leading to altered amphibian metamorphosis KE Moderate

Taxonomic Applicability

Name Scientific Name Evidence Links
African clawed frog Xenopus laevis Strong NCBI

Level of Biological Organization

Biological Organization
Tissue

How this Key Event works

In many ways, this key event fundamentally works the same as key event 1093: Thyroxine (T4) in tissues, decreased: [1]. However, T3 can only be derived from T4, which can occur in any tissue that expresses either type I or II iodothyronine deiodinases (DIO1, DIO2), whereas T4 can only be synthesized in the thyroid gland. The local concentration of T3 in any given cell or tissue will be a function of, (1) local T4 availability, which is a function of plasma T4 concentration and active transport capacity across cell membranes, (2) local DIO1 and/or DIO2 activity, and (3) circulating levels of T3, as a result of remote activation of T4 by either DIO1 or DIO2 and release of T3 to the plasma.

How it is Measured or Detected

Methods that have been previously reviewed and approved by a recognized authority should be included in the Overview section above. All other methods, including those well established in the published literature, should be described here. Consider the following criteria when describing each method: 1. Is the assay fit for purpose? 2. Is the assay directly or indirectly (i.e. a surrogate) related to a key event relevant to the final adverse effect in question? 3. Is the assay repeatable? 4. Is the assay reproducible?

This key event is measured the same as key event 1093: Thyroxine (T4) in tissues, decreased: [2].

Evidence Supporting Taxonomic Applicability

References


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Bastian, T.W., Prohaska, J.R., Georgieff, M.K. and Anderson, G.W., 2010. Perinatal iron and copper deficiencies alter neonatal rat circulating and brain thyroid hormone concentrations. Endocrinology, 151(8), pp.4055-4065.

Bastian, T.W., Anderson, J.A., Fretham, S.J., Prohaska, J.R., Georgieff, M.K. and Anderson, G.W., 2012. Fetal and neonatal iron deficiency reduces thyroid hormone-responsive gene mRNA levels in the neonatal rat hippocampus and cerebral cortex. Endocrinology, 153(11), pp.5668-5680.

Bastian, T.W., Prohaska, J.R., Georgieff, M.K. and Anderson, G.W., 2013. Fetal and neonatal iron deficiency exacerbates mild thyroid hormone insufficiency effects on male thyroid hormone levels and brain thyroid hormone-responsive gene expression. Endocrinology, 155(3), pp.1157-1167.

Crane, H.M., Pickford, D.B., Hutchinson, T.H. and Brown, J.A., 2004. Developmental changes of thyroid hormones in the fathead minnow, Pimephales promelas. General and comparative endocrinology, 139(1), pp.55-60.

Donzelli, R., Colligiani, D., Kusmic, C., Sabatini, M., Lorenzini, L., Accorroni, A., Nannipieri, M., Saba, A., Iervasi, G. and Zucchi, R., 2016. Effect of Hypothyroidism and Hyperthyroidism on Tissue Thyroid Hormone Concentrations in Rat. European thyroid journal, 5(1), pp.27-34.

ESCOBAR, G.M.D., Pastor, R., Obregón, M.J. and REY, F.E.D., 1985. Effects of Maternal Hypothyroidism on the Weight and Thyroid Hormone Content of Rat Embryonic Tissues, before and after Onset of Fetal Thyroid Function*. Endocrinology, 117(5), pp.1890-1900.

Gilbert, M.E., Hedge, J.M., Valentín-Blasini, L., Blount, B.C., Kannan, K., Tietge, J., Zoeller, R.T., Crofton, K.M., Jarrett, J.M. and Fisher, J.W., 2013. An animal model of marginal iodine deficiency during development: the thyroid axis and neurodevelopmental outcome. toxicological sciences, p.kfs335.

Hornung, M.W., Kosian, P.A., Haselman, J.T., Korte, J.J., Challis, K., Macherla, C., Nevalainen, E. and Degitz, S.J., 2015. In vitro, ex vivo, and in vivo determination of thyroid hormone modulating activity of benzothiazoles. Toxicological Sciences, 146(2), pp.254-264.

Kunisue, T., Fisher, J.W., Fatuyi, B. and Kannan, K., 2010. A method for the analysis of six thyroid hormones in thyroid gland by liquid chromatography–tandem mass spectrometry. Journal of Chromatography B, 878(21), pp.1725-1730.

Kunisue, T., Fisher, J.W. and Kannan, K., 2011. Determination of six thyroid hormones in the brain and thyroid gland using isotope-dilution liquid chromatography/tandem mass spectrometry. Analytical chemistry, 83(1), pp.417-424.

Lavado-Autric, R., Calvo, R.M., de Mena, R.M., de Escobar, G.M. and Obregon, M.J., 2012. Deiodinase activities in thyroids and tissues of iodine-deficient female rats. Endocrinology, 154(1), pp.529-536.

Pinna, G., Hiedra, L., Prengel, H., Broedel, O., Eravci, M., Meinhold, H. and Baumgartner, A., 1999. Extraction and quantification of thyroid hormones in selected regions and subcellular fractions of the rat brain. Brain Research Protocols, 4(1), pp.19-28.

Simon, R., Tietge, J., Michalke, B., Degitz, S. and Schramm, K.W., 2002. Iodine species and the endocrine system: thyroid hormone levels in adult Danio rerio and developing Xenopus laevis. Analytical and bioanalytical chemistry, 372(3), pp.481-485.

Saba, A., Donzelli, R., Colligiani, D., Raffaelli, A., Nannipieri, M., Kusmic, C., Dos Remedios, C.G., Simonides, W.S., Iervasi, G. and Zucchi, R., 2014. Quantification of thyroxine and 3, 5, 3′-triiodo-thyronine in human and animal hearts by a novel liquid chromatography-tandem mass spectrometry method. Hormone and Metabolic Research, 46(09), pp.628-634.

Tietge, J.E., Butterworth, B.C., Haselman, J.T., Holcombe, G.W., Hornung, M.W., Korte, J.J., Kosian, P.A., Wolfe, M. and Degitz, S.J., 2010. Early temporal effects of three thyroid hormone synthesis inhibitors in Xenopus laevis. Aquatic Toxicology, 98(1), pp.44-50.

Tietge, J.E., Degitz, S.J., Haselman, J.T., Butterworth, B.C., Korte, J.J., Kosian, P.A., Lindberg-Livingston, A.J., Burgess, E.M., Blackshear, P.E. and Hornung, M.W., 2013. Inhibition of the thyroid hormone pathway in Xenopus laevis by 2-mercaptobenzothiazole. Aquatic toxicology, 126, pp.128-136.