5. thyroid hormone synthesis and action Flashcards
discuss the embryological origins and development of the thyroid
- downgrowth from pharyngeal endoderm of developing tongue (follicular cells)
- C cells from ultimobranchial body (most caudal pharyngeal pouch)
describe th histological appearance of the thryoid
- gland consists of thyroid follicles
- follicles vary in size
- single layer of epithlial cells: follicular cells
- lumen filled with protein rich colloid
- icrovilli on surface next to colloid
describe the structure of the thyroid follicles
- microvilli incrase surface area
- dense capillary network
- deliver nutrients and transport hormones
describe the structure of the parafollicular cells/c cells
- in connective tissue near follicles (parafollicular)
- secrete calcitonin (hormone that lowers blood calcium levels)
what are the 2 thyroid hormones
- triiodothyronine (T3)
- thyroxine (T4)
thyroid hormones are derivitaves of:
amino acids (from tyrosine)
what is the difference between T3 and T4
the number of iodines (T4 = 4 iodine, T3 = 3)
which thyroid hormones is produced more? which one is more biologically active
- T4 produced significantly more than T3
- T3 is more biologically active
- T4 is converted to T3 in liver or at cellular level
describe the synthesis of iodine in relation to thyroid hormones
- iodine circulates in the blood as iodide
- into the follicular cells by secondary active transport
- Na/I symport in the basal membrane (stimulated by TSH)
- concentrates of iodine within colloid = 30 times higher than in blood (iodide trapping)
- excess iodide excreted via kidneys
describe synthesis of thyroglobulin
- follicular cells synthesize thyroglobulin
- processed in golgi apparartus
- exocytosis to follicular lumen
- glycoprotein stored within follicles
- each thyroglobulin contains 120 tyrosine molecules
describe the process of iodination
- process catalyzed by thyroperoxidase
- located in apical membrane
- iodide is oxidized to iodine as hydrogen peroxide is reduced
- iodine is added to tyrosine within thyroglobulin catalyzed by an iodinase enzyme
- iodination occurs as thyroglobulin is secreted into the follicle
what is colloid
- colloid is stored within the follicles
- primarily thyroglobulin (colloid = thyroglobulin)
- triiodothyronine (T3) and thyroxine are bound to the thyroglobulin
- normally only 10% of tyrosines in thyroglobulin are iodinated
- colloid contains enough thyroid hormonen to last 2-3 months
describe how thyroid hormones are secreted
- colloid uptake into follicular cells via endocytosis
- intracellular vesicles fuse with lysosomes
- lysosomal enzymes split thyroid hormones from thyroglobulin
- hormones diffuse across the basal plasma membrane and into the interstitium as a lipid soluble hormone
- the from the interstitium into the blood
what is the name of the transport protein that binds thyroid hormones
thyroid binding globulin
relate concentrations of free thyroid hormone to bound hormone and state which hormone (T3 or T4) is more abundant as a free hormone
- 50 - 60 time higher blood levels of T4 than T3
- more free T3 than T4
- equilibrium between bound and free
how are thyroid hormones metabolised
deiodination:
- thyroxine deiodinated to triiodothyronine (within cells but also liver/kidneys)
- free hormones enter the cells
- thyroxine deiodinated to T3 within the cell
- thyroid gland secretes 90% thyroxine but most will be deiodinated to T3
reverse T3
- remaining T4 deiodinated to reverse T3 (rT3)
- deiodination pathways are therefore a mechanism of regulations (rT3 inactive)
what is the purpose of rT3
regulation of metabolism
- slows metabolism
why are thyroid hormones important
- increase BMR
- maintain body temp
in cases of starvation or illness, how can thyroid hormones help
- lower BMR and conserve energy
- acheived by reducing thyroid hormone concentration or action (lower TSH from pituitary or alter deiodination = mor rT3)
discuss catabolism of thyroid hormone
- deiodinated into diiodotyrosine and monoiodotyrosine
- in the liver and kidneys
- conjugated excretory products
- iodine is either recycled ot excreted via the urine
discuss the actions of thyroid within the cells
- lipid soluble so diffuse into the cells
- intracellular receptors have much higher affinity for T3 (therfore majority of action is by T3)
- bind to DNA to increase or decrease transcription
what are the actions of thyroid hormones
- metabolic actions!!
- development
- growth
- musculoskeletal system
- cardiovascular system
- respiratory system
- nervous systen
- reproductive system
- gastrointestinal system
- integument
what does euthyroid mean
normal thyroid function
how are TRH and TSH regulated
- hypothalamus releases thyrotropin releasing hormone (TRH)
- stimulates adenohypophysis
- secretes thyroid stimulating hormone (TSH aka thyrotropin)
- water soluble hormone in blood
- acts on thyroid gland
what are the 5 actions of TSH
- increased endocytosis and proteolysis of thyroglobulin from colloid
- increased activity of the Na/I symport
- increased iodination of tyrosine
- increased size and secretory activity of thyroid follicular cells
- increased number of follicular cells
this leads to goiter is TSH stim is too high
