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

Research output: Chapter in Book/Report/Conference proceedingAbstractAcademic

Abstract

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 at 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.
LanguageEnglish
Title of host publicationBook of Abstracts of the 49th Congress of the European Societies of Toxicology (EUROTOX)
EditorsR. Roberts
PagesS151-S151
Volume221
DOIs
Publication statusPublished - 2013
Event49th EUROTOX, Interlaken, Switzerland -
Duration: 1 Sep 20134 Sep 2013

Conference

Conference49th EUROTOX, Interlaken, Switzerland
Period1/09/134/09/13

Fingerprint

Animal Testing Alternatives
Thyroid Gland
Cell Proliferation
Thyroid Hormone Receptors
Weights and Measures
Thyrotropin
Thyrotropin Receptors
Thyrotropin-Releasing Hormone
Triiodothyronine
Thyroxine
In Vitro Techniques

Cite this

Jomaa, B., Aarts, M. M. J. G., de Haan, L. H. J., Peijnenburg, A. A. C. M., Bovee, T. F. H., Murk, A. J., & Rietjens, I. M. C. M. (2013). In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing. In R. Roberts (Ed.), Book of Abstracts of the 49th Congress of the European Societies of Toxicology (EUROTOX) (Vol. 221, pp. S151-S151) https://doi.org/10.1016/j.toxlet.2013.05.309
Jomaa, B. ; Aarts, M.M.J.G. ; de Haan, L.H.J. ; Peijnenburg, A.A.C.M. ; Bovee, T.F.H. ; Murk, A.J. ; Rietjens, I.M.C.M. / In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing. Book of Abstracts of the 49th Congress of the European Societies of Toxicology (EUROTOX). editor / R. Roberts. Vol. 221 2013. pp. S151-S151
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abstract = "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 at 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.",
author = "B. Jomaa and M.M.J.G. Aarts and {de Haan}, L.H.J. and A.A.C.M. Peijnenburg and T.F.H. Bovee and A.J. Murk and I.M.C.M. Rietjens",
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Jomaa, B, Aarts, MMJG, de Haan, LHJ, Peijnenburg, AACM, Bovee, TFH, Murk, AJ & Rietjens, IMCM 2013, In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing. in R Roberts (ed.), Book of Abstracts of the 49th Congress of the European Societies of Toxicology (EUROTOX). vol. 221, pp. S151-S151, 49th EUROTOX, Interlaken, Switzerland, 1/09/13. https://doi.org/10.1016/j.toxlet.2013.05.309

In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing. / Jomaa, B.; Aarts, M.M.J.G.; de Haan, L.H.J.; Peijnenburg, A.A.C.M.; Bovee, T.F.H.; Murk, A.J.; Rietjens, I.M.C.M.

Book of Abstracts of the 49th Congress of the European Societies of Toxicology (EUROTOX). ed. / R. Roberts. Vol. 221 2013. p. S151-S151.

Research output: Chapter in Book/Report/Conference proceedingAbstractAcademic

TY - CHAP

T1 - In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing

AU - Jomaa, B.

AU - Aarts, M.M.J.G.

AU - de Haan, L.H.J.

AU - Peijnenburg, A.A.C.M.

AU - Bovee, T.F.H.

AU - Murk, A.J.

AU - Rietjens, I.M.C.M.

PY - 2013

Y1 - 2013

N2 - 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 at 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.

AB - 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 at 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.

U2 - 10.1016/j.toxlet.2013.05.309

DO - 10.1016/j.toxlet.2013.05.309

M3 - Abstract

VL - 221

SP - S151-S151

BT - Book of Abstracts of the 49th Congress of the European Societies of Toxicology (EUROTOX)

A2 - Roberts, R.

ER -

Jomaa B, Aarts MMJG, de Haan LHJ, Peijnenburg AACM, Bovee TFH, Murk AJ et al. In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing. In Roberts R, editor, Book of Abstracts of the 49th Congress of the European Societies of Toxicology (EUROTOX). Vol. 221. 2013. p. S151-S151 https://doi.org/10.1016/j.toxlet.2013.05.309