24.3 Flashcards
Iodine is an ___ element.
Essential
Goitre is a classic sign of ___ deficiency. ___ ___ ___ stimulates hypertrophy and hyperplasia of the thyroid.
Iodine
Thyroid stimulating hormone
T4/T3 from the thyroid gland exert ___ feedback on the ___ and ___ gland to decrease secretion of ___ and ___ respectively.
Negative feedback
Hypothalamus and thyroid gland
TRH and TSH respectively
Thyroid releasing hormone is produced by neurons from the ___ ___.
Paraventricular nucleus
Thyroid hormone can enter target cells by transporters like ___ ___ (MCT8) or organic anion transporter polypeptide (OATPs).
Monocarboxylate transporter
Thyroid peroxidase catalyses the ___ of thyroglobulin to ___ or ___, AND catalyses the ___ reaction.
Iodination
Thyroglobulin + I- -> MIT or DIT
Coupling e.g. of DIT and DIT -> T4, or MIT and DIT -> T3
Usually T_ is synthesised, most of thyroid hormones in circulation is T_. T_ is more potent than T_.
T4 is usually synthesised, most T4 in circulation.
T3 is more potent thant T4.
T4 is usually convered ___ to T3, in the ___ using deiodinases.
Intracellularly
Cytosol - using deiodinases
The site of action of T3 is ___ ___ receptors in the ___ of the cell. ___ ___ receptors bind to the ___ region of the target gene and dimerise with ___ -> effects on gene transcription.
Thyroid hormone receptors in the nucleus
Thyroid hormone receptors bind to the promoter region and dimerise with RXR (a receptor)
T4 is important for some ___-___ actions, but most ___ actions depend on T3.
T4 - some non-genomic actions, but otherwise low activity
T3 - most genomic actions
How many types of deiodinase enzymes are in the cytosol of different cells? All of them only deiodinate the /’ position, but at different rings. Expression is different though, so you can get different thyroid hormones in difference cells.
3!
5/5’
What are the major physiological actions of thyroid hormone? How?
Calorigenic action - increase O2 consumption of almost all metabolically active tissue, increase energy consumption and substrate use, cellular respiration.
CV system - increase heart rate and heart weight
How? Increased expression of genes of structural/function proteins and proteins in thermogenesis, and mitochondrial biogenesis
Transcriptional regulation by TH receptors?
Non-active THR forms a dimer with RXR and binds to the thyroid responsive element (TRE) upstream of the transcriptional start site
The THR/RXR dimer binds to the co-repressor complex are prevents transcription of the target gene
When T3 binds to THR, it replaces the corepressor complex with the coactivator complex to start transcription of the targen gene.
___ alphaVbeta3 is a cell surface receptor for ___ ___.
Integrin
Thyroid hormone
Binding causes intracellular pathways like PLC/PKC -> ERK, etc.