Thyroid Hormone Signalling Flashcards
Does this show the pathway of peptide or steriod hormones?
Peptide hormones
Does this show the pathway of peptide or steriod hormones?
Steroid hormnes
How is thyroid hormone made?
It is an amino acid hormone
Draw a diagram of the thyroid Hormone Signalling Pathway
- The hydrophobic thyroid hormones can cross the lipid membrane or by transporters that actively transport tyroid hormone into the target cell
- T4 is subject to activity of deiodinase enzymes
- The thyroid hormone receptor (TR) is bound to the thyroid hormone response elements (TRE) within regulatory regions of target genes
- When there are low levels of thyroid hormone TR will be inactive and bound in a corepressor complex. No expression of target genes
- When TR bind T3 a conformational change occurs and the co-repressor complex falls apart. The now active TR can bind to a coactivator
- Transcriptional machinery can acess gene promoters and drive gene expression
How does thyroid hormone enter the cell?
- Thyroid hormones are hydrophobic – can cross cell membrane.
- Can also be transported via specialist membrane transporters e.g. MCT8.
- Expression of these membrane transporters both spatially & temporally regulated.
Describe the local activation of thyroid hormone
- Circulating T4 converted locally to T3 by deiodinases (D1/D2).
- T4 can be converted to inactive reverse T3 (rT3) by type 3 5-deiodinase (D3).
- Activity of deiodinases is highly regulated – ubiquitination & degradation.
Describe thyroid hormone receptors
- Multiple isoforms are expressed from single TR gene.
- Members of nuclear hormone receptor superfamily.
- Modular structure – functional domains.
- Different isoforms are expressed in different temporal and spatial patterns – and show different potency (α>β).
What is the thyroid hormone response element?
- TR binds to consensus sequence within genome.
- This binding site = thyroid hormone response element (TRE).
- TRE usually exists as direct or everted repeat.
- TR binds to TRE in absence of ligand.
Describe inactive thyroid hormone receptors
Describe active thyroid hormone receptors
Describe non-genomic thyroid hormone signalling
- Classical genomic actions by thyroid hormone via regulation of gene expression are slow.
- Recent observations of rapid cellular responses to thyroid hormone suggest alternative non-genomic mechanism of action.
- Example: integrin αvβ5 has been identified as a cell membrane receptor for T4 – activates MAPK signalling to promote cell growth.
- Other cell signalling cascades activated by thyroid hormone include PI3K and cyclic-AMP.
- Thyroid hormone also has direct actions on mitochondria
Describe the effects of thyroid hormone signalling on heart contraction
Thyroid hormone increases force of heart contraction.
Thyroid hormone enters cardiac muscle cells→T4 converted to T3 → nucleus→Binds to and activates TR – localised to TRE of target genes→Activates target gene expression e.g. myosins
How does hyperrthyroidism change heart contraction?
palpitations, rapid heart rate
How does hypothyroidism change heart contraction?
It causes weakness, lethargy, decreased activity
Which 2 amino acids are amino acid hormones generally derived from?
Tyrosine or tryptophan
Draw a table of amino acid hormones, the amino acid they are derived from and their site of synthesis
Draw a table of amino acid hormones and their receptor types
Describe histone acetylation
- Acetylation of histone tails by histone acetyltrnasferases (HATs) reduces inteaction between DNA and histone producing open active chromatin
- Removal of acetyl groups by histone deacetylases (HDACs) promotes stronger interactions between DNA and histone produce close inactive chromatin
