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Key Event Title
Decreased, Thyroxine (T4) in tissues
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
|African clawed frog||Xenopus laevis||Moderate||NCBI|
Key Event Description
Thyroxine (T4) is the pro-hormone form that is converted to the active hormone triiodothyronine (T3) via intracellular enzymatic outer ring deiodination by either type I or II deiodinases. The presence of T4 in cells/tissues is the predominant input into the biochemical pathway leading to regulation of gene expression by T3 and thyroid receptors.
How It Is Measured or Detected
Tissues typically contain low levels of thyroid hormones and are generally complex sample matrices, making analyses of thyroid hormones in tissues challenging. This requires special consideration for the composition of the specific tissue in order to employ the proper sample preparation technique. Ideally, analyses of tissue TH is a two-step process starting with extraction and then subsequent analyses. Extraction procedures for thyroid hormones, their precursors and analogues have been demonstrated in whole body homogenates of fish or tadpoles using ethanol extractions, tadpole and rat thyroid gland tissue using proteolytic digestions and rat peripheral tissues using methanol-chloroform extractions (see attached reference table for details). Analyses of sample extracts have been performed using radioimmunoassay (RIA), liquid-chromatography inductively coupled mass spectrometry (HPLC-ICP/MS) and liquid chromatography tandem mass spectrometry (UPLC/HPLC-MS/MS). These methods generally require addition of radioisotope labeled compounds (RIA) or stable isotope labeled compounds (LC-MS/MS) to samples prior to the extraction procedure in order to correct for recovery, so the extraction and analysis steps are not entirely independent of each other. Another consideration for the technique employed to measure thyroid hormones is that RIA methods are only capable of measuring a single analyte at a time and is typically either T3 or T4 whereas LC-ICP/MS and LC-MS/MS methods allow quantitation of thyroid hormones, precursors and metabolites all in the same sample (see attached reference table for details).
Domain of Applicability
The essentiality of this key event applies during thyroid-mediated metamorphosis in amphibians and especially African clawed frog (Xenopus laevis), which lends the basis for this key event leading to altered metamorphosis. However, direct measurements of this key event are not routine or typical. The support for this key event exists primarily as biological plausibility and thyroid endocrinology dogma.
Additionally, it is accepted that this key event can apply to mammalian pre and postnatal neurodevelopment but AOPs leading to this adverse outcome (e.g., AOP 42) specify neurological tissue in the key event title (KE 280), whereas this key event is applicable across tissue types.
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