Development and validation of an LC-MS/MS methodology for the quantification of thyroid hormones in dko MCT8/OATP1C1 mouse brain

Angelis, Meri De; Maity-Kumar, Gandhari; Schriever, Sonja C.; Kozlova, Elena; Müller, Timo; Pfluger, Paul T.; Currás-Collazo, Margarita; Schramm, Karl‐Werner

doi:10.1016/j.jpba.2022.115038

Cited by 4 publications

(2 citation statements)

References 35 publications

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“…For quantification of thyroid hormone levels, tissues were dissected, snap frozen in liquid nitrogen, and stored at-80 °C. For brain analysis, after homogenization of whole-brains at around −200 °C, about 100 mg was used for LC-MS/MS quantification of thyroid hormones (TH) using the Agilent 1290 Infinity II LC system interfaced with an Agilent 6470 triple quadrupole tandem mass spectrometer as described previously [ 20 ]. For the analysis of liver, heart, BAT and eWAT a nanoAcquity system interfaced with a QTof2 mass detector was used as previously described [ 21 , 22 ].…”

Section: Methodsmentioning

confidence: 99%

Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome

Maity-Kumar

Ständer

DeAngelis

et al. 2022

Molecular Metabolism

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Section: Methodsmentioning

confidence: 99%

Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome

Maity-Kumar

Ständer

DeAngelis

et al. 2022

Molecular Metabolism

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“…THs and their derivatives selectively accumulate in brain regions over blood (13,21,(26)(27)(28)(29). Tissue levels of TH vary significantly by brain area (30).…”

Section: Levels Of Ths and Tams In Adult Rat Brainmentioning

confidence: 99%

Nongenomic roles of thyroid hormones and their derivatives in adult brain: are these compounds putative neurotransmitters?

Martin,

Sarkar

2023

Front. Endocrinol.

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We review the evidence regarding the nongenomic (or non-canonical) actions of thyroid hormones (thyronines) and their derivatives (including thyronamines and thyroacetic acids) in the adult brain. The paper seeks to evaluate these compounds for consideration as candidate neurotransmitters. Neurotransmitters are defined by their (a) presence in the neural tissue, (b) release from neural tissue or cell, (c) binding to high-affinity and saturable recognition sites, (d) triggering of a specific effector mechanism and (e) inactivation mechanism. Thyronines and thyronamines are concentrated in brain tissue and show distinctive patterns of distribution within the brain. Nerve terminals accumulate a large amount of thyroid hormones in mature brain, suggesting a synaptic function. However, surprisingly little is known about the potential release of thyroid hormones at synapses. There are specific binding sites for thyroid hormones in nerve-terminal fractions (synaptosomes). A notable cell-membrane binding site for thyroid hormones is integrin αvβ3. Furthermore, thyronines bind specifically to other defined neurotransmitter receptors, including GABAergic, catecholaminergic, glutamatergic, serotonergic and cholinergic systems. Here, the thyronines tend to bind to sites other than the primary sites and have allosteric effects. Thyronamines also bind to specific membrane receptors, including the trace amine associated receptors (TAARs), especially TAAR1. The thyronines and thyronamines activate specific effector mechanisms that are short in latency and often occur in subcellular fractions lacking nuclei, suggesting nongenomic actions. Some of the effector mechanisms for thyronines include effects on protein phosphorylation, Na+/K+ ATPase, and behavioral measures such as sleep regulation and measures of memory retention. Thyronamines promptly regulate body temperature. Lastly, there are numerous inactivation mechanisms for the hormones, including decarboxylation, deiodination, oxidative deamination, glucuronidation, sulfation and acetylation. Therefore, at the current state of the research field, thyroid hormones and their derivatives satisfy most, but not all, of the criteria for definition as neurotransmitters.

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Two novel in vitro assays to screen chemicals for their capacity to inhibit thyroid hormone transmembrane transporter proteins OATP1C1 and OAT4

Wagenaars,

Cenijn,

Chen

et al. 2024

Arch Toxicol

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Early brain development depends on adequate transport of thyroid hormones (THs) from the maternal circulation to the fetus. To reach the fetal brain, THs have to cross several physiological barriers, including the placenta, blood–brain-barrier and blood–cerebrospinal fluid-barrier. Transport across these barriers is facilitated by thyroid hormone transmembrane transporters (THTMTs). Some endocrine disrupting chemicals (EDCs) can interfere with the transport of THs by THTMTs. To screen chemicals for their capacity to disrupt THTMT facilitated TH transport, in vitro screening assays are required. In this study, we developed assays for two THTMTs, organic anion transporter polypeptide 1C1 (OATP1C1) and organic anion transporter 4 (OAT4), both known to play a role in the transport of THs across barriers. We used overexpressing cell models for both OATP1C1 and OAT4, which showed an increased uptake of radiolabeled T4 compared to control cell lines. Using these models, we screened various reference and environmental chemicals for their ability to inhibit T4 uptake by OATP1C1 and OAT4. Tetrabromobisphenol A (TBBPA) was identified as an OATP1C1 inhibitor, more potent than any of the reference chemicals tested. Additionally perfluorooctanesulfonic acid (PFOS), perfluoroctanic acid (PFOA), pentachlorophenol and quercetin were identified as OATP1C1 inhibitors in a similar range of potency to the reference chemicals tested. Bromosulfophthalein, TBBPA, PFOA and PFOS were identified as potent OAT4 inhibitors. These results demonstrate that EDCs commonly found in our environment can disrupt TH transport by THTMTs, and contribute to the identification of molecular mechanisms underlying TH system disruption chemicals.

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Development and validation of an LC-MS/MS methodology for the quantification of thyroid hormones in dko MCT8/OATP1C1 mouse brain

Cited by 4 publications

References 35 publications

Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome

Validation of Mct8/Oatp1c1 dKO mice as a model organism for the Allan-Herndon-Dudley Syndrome

Nongenomic roles of thyroid hormones and their derivatives in adult brain: are these compounds putative neurotransmitters?

Two novel in vitro assays to screen chemicals for their capacity to inhibit thyroid hormone transmembrane transporter proteins OATP1C1 and OAT4

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