Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways

Vickers, Alison E. M.; Heale, Jason; Sinclair, John; Morris, Sherri J.; Rowe, Josh; Fisher, Ron

doi:10.1016/j.taap.2012.01.029

Cited by 26 publications

(25 citation statements)

References 39 publications

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“…This is somewhat different from observations in human thyroid cells and rat FRTL-5 cells cultured in vitro where short-term treatment with MMI increased the expression of thyroid peroxidase as well as thyroglobulin (Leer et al 1991). However, recent studies on human thyroid slices have shown that the effect of MMI on the expression of thyroid-specific genes may vary according to treatment dose and duration (Vickers et al 2012).…”

Section: Discussioncontrasting

confidence: 78%

“…The anti-thyroid drug MMI can be absorbed from the gastrointestinal tract and it accumulates in the thyroid gland where it inhibits TH synthesis by interfering with the action of thyroid peroxidase (Nagasaka & Hidaka 1976, Vickers et al 2012. It has been shown in humans and rats that MMI is rapidly metabolised and that a major part is excreted via urine (Skellern & Steer 1981, Hengstmann & Hohn 1985, Cooper 2005, Kusmierek & Bald 2007.…”

Section: Discussionmentioning

confidence: 99%

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Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues

Herck

Geysens²,

Bald³

et al. 2013

Journal of Endocrinology

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Methimazole (MMI) is an anti-thyroid drug used in the treatment of chronic hyperthyroidism. There is, however, some debate about its use during pregnancy as MMI is known to cross the mammalian placenta and reach the developing foetus. A similar problem occurs in birds, where MMI is deposited in the egg and taken up by the developing embryo. To investigate whether maternally derived MMI can have detrimental effects on embryonic development, we treated laying hens with MMI (0.03% in drinking water) and measured total and reduced MMI contents in the tissues of hens and embryos at different stages of development. In hens, MMI was selectively increased in the thyroid gland, while its levels in the liver and especially brain remained relatively low. Long-term MMI treatment induced a pronounced goitre with a decrease in thyroxine (T 4 ) content but an increase in thyroidal 3,5,3 0 -triiodothyronine (T 3 ) content. This resulted in normal T 3 levels in tissues except in the brain. In chicken embryos, MMI levels were similar in the liver and brain. They gradually decreased during development but always remained above those in the corresponding maternal tissues. Contrary to the situation in hens, T 4 availability was only moderately affected in embryos. Peripheral T 3 levels were reduced in 14-day-old embryos but normal in 18-day-old embryos, while brain T 3 content was decreased at all embryonic stages tested. We conclude that all embryonic tissues are exposed to relatively high doses of MMI and its oxidised metabolites. The effect of maternal MMI treatment on embryonic thyroid hormone availability is most pronounced for brain T 3 content, which is reduced throughout the embryonic development period.

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Section: Discussioncontrasting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues

Herck

Geysens²,

Bald³

et al. 2013

Journal of Endocrinology

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“…Possible that coloured chemicals could interfere with the accurate quantification of colour formation. Vickers et al, 2012;Paul et al, 2013;Tietge et al, 2012;Doerge et al, 2002b; Sodium Iodide Symporter (NIS) Activity Assays…”

Section: Assay Features/ Limitationsmentioning

confidence: 99%

“…In addition an assay combining TPO activity assay with gene expression analysis using microarray hybridisation has been developed by (Song M. et al, 2011). Another assay using substrate developed for spectroscopic detection systems has been developed by Vickers et al; Proposed/potential regulatory purpose This assay may be more appropriate as a confirmatory assay following screening. Substances that inhibit TPO may result in hypothyroxinemia/hypothyroidism, with potential deleterious effects if exposure occurs during neurodevelopment.…”

Section: Assay Included In Oecd Drps?mentioning

confidence: 99%

“…However, while the use of porcine tissue for TPO assays seems to give qualitatively the same results as obtained with rat tissue, there were differences in the relative potency for TPO inhibition that could result in some compounds being missed if only porcine tissue is used to screen chemicals. A recent report suggested that rat TPO may be more responsive than human TPO to xenobiotic inhibitors MMI and PTU (Vickers et al, 2012), but assessment with a larger chemical set would be necessary to evaluate this hypothesis. …”

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confidence: 99%

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New Scoping Document on in vitro and ex vivo Assays for the Identification of Modulators of Thyroid Hormone Signalling

2014

OECD Series on Testing and Assessment

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Complete document available on OLIS in its original formatThis document and any map included herein are without prejudice to the status of or sovereignty over any territory, to the delimitation of international frontiers and boundaries and to the name of any territory, city or area. About the OECDThe Organisation for Economic Co-operation and Development (OECD) is an intergovernmental organisation in which representatives of 34 industrialised countries in North and South America, Europe and the Asia and Pacific region, as well as the European Commission, meet to co-ordinate and harmonise policies, discuss issues of mutual concern, and work together to respond to international problems. Most of the OECD's work is carried out by more than 200 specialised committees and working groups composed of member country delegates. Observers from several countries with special status at the OECD, and from interested international organisations, attend many of the OECD's workshops and other meetings. Committees and working groups are served by the OECD Secretariat, located in Paris, France, which is organised into directorates and divisions. This publication was developed in the IOMC context. The contents do not necessarily reflect the views or stated policies of individual IOMC Participating Organisations.The Inter-Organisation Programme for the Sound Management of Chemicals (IOMC) was established in 1995 following recommendations made by the 1992 UN Conference on Environment and Development to strengthen co-operation and increase international co-ordination in the field of chemical safety. The Participating Organisations are FAO, ILO, UNDP, UNEP, UNIDO, UNITAR, WHO, World Bank and OECD. The purpose of the IOMC is to promote co-ordination of the policies and activities pursued by the Participating Organisations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment. FOREWORDThis new scoping document aims at bringing forward relevant in vitro and ex vivo thyroid assays to the attention of OECD member countries, to provide recommendations for their development/use, and also, to identify aspects/blocks of the thyroid signalling pathways that are not covered and would require further development of thyroid assays. ACRONYMS, ABBREVIATIONS AND DEFINITIONS ADMEAbsorption, distribution, metabolism and excretion AhR aryl hydrocarbon receptor AMA Amphibian Metamorphosis Assay (OECD TG 231) AOP adverse outcome pathway AOP is a sequence of events from the exposure of an individual or population to a chemical substance through a final adverse (toxic) effect at the individual level (for human health) or population level (for ecotoxicological endpoints). AR androgen receptorAssay An experimental system that can be used to obtain a range of information from chemical properties through the adverse effects of a substance. The terms 'assay' and 'test method' may be used interchangeably for wildlife as well as for mammalian studies (OECD, 2005) Indicators of Hormonal activit...

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AOP Report: Thyroperoxidase Inhibition Leading to Altered Visual Function in Fish Via Altered Retinal Layer Structure

Gölz

Baumann

Pannetier

et al. 2022

Enviro Toxic and Chemistry

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Thyroid hormones (THs) are involved in the regulation of many important physiological and developmental processes, including vertebrate eye development. Thyroid hormone system–disrupting chemicals (THSDCs) may have severe consequences, because proper functioning of the visual system is a key factor for survival in wildlife. However, the sequence of events leading from TH system disruption (THSD) to altered eye development in fish has not yet been fully described. The development of this adverse outcome pathway (AOP) was based on an intensive literature review of studies that focused on THSD and impacts on eye development, mainly in fish. In total, approximately 120 studies (up to the end of 2021) were used in the development of this AOP linking inhibition of the key enzyme for TH synthesis, thyroperoxidase (TPO), to effects on retinal layer structure and visual function in fish (AOP‐Wiki, AOP 363). In a weight‐of‐evidence evaluation, the confidence levels were overall moderate, with ample studies showing the link between reduced TH levels and altered retinal layer structure. However, some uncertainties about the underlying mechanism(s) remain. Although the current weight‐of‐evidence evaluation is based on fish, the AOP is plausibly applicable to other vertebrate classes. Through the re‐use of several building blocks, this AOP is connected to the AOPs leading from TPO and deiodinase inhibition to impaired swim bladder inflation in fish (AOPs 155–159), together forming an AOP network describing THSD in fish. This AOP network addresses the lack of thyroid‐related endpoints in existing fish test guidelines for the evaluation of THSDCs. Environ Toxicol Chem 2022;41:2632–2648. © 2022 SETAC

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Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways

Cited by 26 publications

References 39 publications

Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues

Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues

New Scoping Document on in vitro and ex vivo Assays for the Identification of Modulators of Thyroid Hormone Signalling

AOP Report: Thyroperoxidase Inhibition Leading to Altered Visual Function in Fish Via Altered Retinal Layer Structure

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