5. thyroid hormone synthesis and action

Question 1

discuss the embryological origins and development of the thyroid

Answer 1

• downgrowth from pharyngeal endoderm of developing tongue (follicular cells)
• C cells from ultimobranchial body (most caudal pharyngeal pouch)

Question 2

describe th histological appearance of the thryoid

Answer 2

• 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

Question 3

describe the structure of the thyroid follicles

Answer 3

• microvilli incrase surface area
• dense capillary network
• deliver nutrients and transport hormones

Question 4

describe the structure of the parafollicular cells/c cells

Answer 4

• in connective tissue near follicles (parafollicular)
• secrete calcitonin (hormone that lowers blood calcium levels)

Question 5

what are the 2 thyroid hormones

Answer 5

• triiodothyronine (T3)
• thyroxine (T4)

Question 6

thyroid hormones are derivitaves of:

Answer 6

amino acids (from tyrosine)

Question 7

what is the difference between T3 and T4

Answer 7

the number of iodines (T4 = 4 iodine, T3 = 3)

Question 8

which thyroid hormones is produced more? which one is more biologically active

Answer 8

• T4 produced significantly more than T3
• T3 is more biologically active
• T4 is converted to T3 in liver or at cellular level

Question 9

describe the synthesis of iodine in relation to thyroid hormones

Answer 9

• 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

Question 10

describe synthesis of thyroglobulin

Answer 10

• follicular cells synthesize thyroglobulin
• processed in golgi apparartus
• exocytosis to follicular lumen
• glycoprotein stored within follicles
• each thyroglobulin contains 120 tyrosine molecules

Question 11

describe the process of iodination

Answer 11

• 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

Question 12

what is colloid

Answer 12

• 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

Question 13

describe how thyroid hormones are secreted

Answer 13

• 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

Question 14

what is the name of the transport protein that binds thyroid hormones

Answer 14

thyroid binding globulin

Question 15

relate concentrations of free thyroid hormone to bound hormone and state which hormone (T3 or T4) is more abundant as a free hormone

Answer 15

• 50 - 60 time higher blood levels of T4 than T3
• more free T3 than T4
• equilibrium between bound and free

Question 16

how are thyroid hormones metabolised

Answer 16

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)

Question 17

what is the purpose of rT3

Answer 17

regulation of metabolism
- slows metabolism

Question 18

why are thyroid hormones important

Answer 18

• increase BMR
• maintain body temp

Question 19

in cases of starvation or illness, how can thyroid hormones help

Answer 19

• lower BMR and conserve energy
• acheived by reducing thyroid hormone concentration or action (lower TSH from pituitary or alter deiodination = mor rT3)

Question 20

discuss catabolism of thyroid hormone

Answer 20

• deiodinated into diiodotyrosine and monoiodotyrosine
• in the liver and kidneys
• conjugated excretory products
• iodine is either recycled ot excreted via the urine

Question 21

discuss the actions of thyroid within the cells

Answer 21

• 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

Question 22

what are the actions of thyroid hormones

Answer 22

• metabolic actions!!
• development
• growth
• musculoskeletal system
• cardiovascular system
• respiratory system
• nervous systen
• reproductive system
• gastrointestinal system
• integument

Question 23

what does euthyroid mean

Answer 23

normal thyroid function

Question 24

how are TRH and TSH regulated

Answer 24

• hypothalamus releases thyrotropin releasing hormone (TRH)
• stimulates adenohypophysis
• secretes thyroid stimulating hormone (TSH aka thyrotropin)
• water soluble hormone in blood
• acts on thyroid gland

Question 25

what are the 5 actions of TSH

Answer 25

• 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