API

Relationship: 1143

Title

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T4 in serum, Decreased leads to Decreased, Thyroxine (T4) in tissues

Upstream event

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T4 in serum, Decreased

Downstream event

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Decreased, Thyroxine (T4) in tissues

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Adjacency Weight of Evidence Quantitative Understanding
Thyroperoxidase inhibition leading to altered amphibian metamorphosis adjacent Moderate Low

Taxonomic Applicability

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Sex Applicability

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Life Stage Applicability

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Key Event Relationship Description

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Evidence Supporting this KER

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Biological Plausibility

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Thyroid hormone uptake from plasma into tissues is mediated by a number of active transport proteins exhibiting unique profiles depending on tissue type and timing of development (Hennemann et al., 2001; Visser et al., 2011; Connors et al., 2010). The scientific literature suggests that specific regulation of transporter profiles plays a role in timing of thyroid hormone uptake into specific tissues. However, when thyroid hormone levels in the plasma are deficient, it is highly plausible that tissue levels of thyroid hormone will also be deficient. Studies have shown a strong relationship between plasma and tissue thyroid hormone concentrations, but emphasize the complexity of the relationship due to presumptive local regulation of both active transport and subsequent biochemical modification of thyroid hormone within cells by deiodinase enzymes.

Empirical Evidence

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Uncertainties and Inconsistencies

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Quantitative Understanding of the Linkage

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Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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References

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