Topic 7.3 Flashcards
Which trace element is necessary for normal thyroid hormone synthesis?
Iodine
What is the functional unit of the thyroid gland?
Thyroid follicle
What fills the follicular lumen?
Colloid
What is colloid made of?
thyroglobulin
What cells can we find scattered in the thyroid gland?
parafollicular, C cells
What do C cells secrete?
Calcitonin (peptide hormone)
Where does the start of thyroid hormone synthesis happen?
extracellularly
3 types of iodo-thyronines
- T4, thyroxine, 3,5,3’,5’-tetra-iodothyronine
- T3, 3,5,3’-tri-iodothyronine
- Reverse T3, 3,3’,3’-tri-iodothyronine
3 transporters useful for iodine transportation
- Na/I transporters (NIS)
- Na+,K+, ATPase
- Pendrin : I/Cl
What molecule stimulates expression of the NIS?
TSH
What does thyroid peroxidase catalyze? (3)
- iodide oxydation
- thyroglobulin iodination
- iodothyronine coupling
Where is thyroid peroxidase located?
in the apical membrane
What is T3 a coupling of?
DIT + MIT
What is T4 a coupling of?
DIT + DIT
First step of synthesis of iodothyronines
Iodide is oxidized and incorporated into tyrosine residues w/in thyroglobulin in the lumen
What is the electron acceptor of the follicular membrane?
H202
When is thyroglobulin degraded?
Once endocytotic vesicle fuses with lysosome, then there’s proteolysis
Which enzyme catalyzes deioniodination of MIT and DIT?
iodo-tyrosine deiodinase
What is peripheral conversion?
T4 is converted into active T3
Which enzymes catalyze peripheral conversion?
tyrosine-specific deiodinases
Where can we find Type 1 deiodinase? (3)
- Liver
- Kidneys
- Thyroid gland
Where can we find Type 2 deiodinase?
glial cells of the CNS
Roles of type 2 deiodinase (2)
- Maintains intracellular T3
- mediates T4 to feedback on secretion of TSH
What receptors do thyroid hormones use to act?
Nuclear receptors
Structure of nuclear receptor (3)
- Variable region
- DNA binding domain
- Hormone binding domain
What happens to T4 once it enters its target cell?
Most of it is converted to T3 by 5’/3’-monodeiodinase
Where do tyrosine receptors bind on DNA?
thyroid response elements (TRE) in the promoter region
How much of the tyrosine bound to receptor is T3?
90%
6 effects of thyroid hormones
- increased BMR
- increased thermogenesis
- decreased plasma [glycerol] and [cholesterol] but increased plasma [FA]
- Increase gluconeogenesis and glycogenolysis
- Growth
- increased cardiovascular effects
What is TRH?
thyrotropin releasing hormonone
What does TRH bind to?
Gq coupled receptor on the thyrotrophic membrane
What does TSH bind to?
Gs coupled receptors on the thyroid follicular cells
What inhibits TSH release? (2)
- SST
- Dopamine
What is hypothyroidism often due to
Autoimmunity : hashimoto’s disease
What is Grave’s disease?
Autoimune disease in which thyroid stimulating immunoglobulins form against the TSH receptor in the thyroid gland : continual activation
