lecture 21: iodine

Question 1

function of iodine

Answer 1

synthesis of thyroid hormones

Question 2

T3 and T4

Answer 2

iodinated derivatives of tyrosine, T3 active

Question 3

hypothyroidism

Answer 3

result from insufficient dietary iodine or ingestion of goitrogens (in staple foods)

Question 4

thyroid peroxidase

Answer 4

1) incorporate iodide into thyroglobulin protein
2) condenses residues within TG to form T3 or T4

Question 5

release of thyroid hormones

Answer 5

iodinated TG taken into thyroid cells, fuse with lysosomes, TG broken down, release of free thyroid hormones into circulation (T4 dominant)

Question 6

deiodination

Answer 6

T4 de-iodinated to generate active T3
de-iodinate T3 to T2 (inactive)

can activate and deactivate

Question 7

type 1 deiodinase

Answer 7

contributes significantly to circulating T3 conc

kidney, liver, thyroid gland

Question 8

how are thyroid hormones carried in the blood?

Answer 8

3 proteins
1) thyroid-binding globulin
2) thyroid-binding pre-albumin
3) albumin

T4 bound more tightly (long plasma half life)

Question 9

goitrogens

Answer 9

competitively inhibit iodide uptake by the thyroid gland

Question 10

type 2 deiodinase

Answer 10

convert T4 to T3 for local tissue use
brain, pituitary, brown adipose tissue

Question 11

type 3 deiodinase

Answer 11

operates exclusively on inner ring to inactivate thyroid hormones

Question 12

thyroid stimulating hormone (TSH)

Answer 12

from pituitary, acts on thyroid gland
regulates TH levels through negative feedback
T4 travels to pituitary to become T3

Question 13

Elevated TSH levels indicate hypothyroidism, whereas levels are low in hyperthyroidism. Why would this be the case?

Answer 13

TSH levels are controlled by negative feedback – lack of negative feedback, not producing thyroid hormone, there is no negative feedback to regulate TSH > elevated TSH

Question 14

differentiation of tissues in TH

Answer 14

type 1 deiodinase altered during fasting, but not type 2, so brain and pituitary can still function

Question 15

thyroid nuclear receptors (TR)

Answer 15

binds T3 in the nucleus, already bound to TREs as a heterodimer with RXR

Question 16

thyroid hormone response elements (TREs)

Answer 16

DNA sequences in the control regions of target genes
usually found in pairs
TR must select TREs to regulate

Question 17

heterodimers for TREs

Answer 17

in the presence of T3, TR-RXR heterodimers bind to TREs
binding of T3 leads to recruitment of co-activators, promoting transcription

Question 18

TH in regulation of lipids

Answer 18

Thyroid hormone stimulates fatty acid synthesis by enhancing expression of the genes involved in this process

enhances lipolysis

Question 19

substrate cycling

Answer 19

increase by hyperthyroidism, hypo decreases

Question 20

carbohydrates and TH

Answer 20

glycolysis and gluconeogenesis stimulated by TH

increase substrate cycling

Question 21

proteins and TH

Answer 21

hyperthyroidism: increase in mRNA synthesis, protein turnover

overall effect of elevated T3 is catabolic

Question 22

goiter

Answer 22

enlargement of thyroid gland, iodine deficiency
low plasma levels TH > increased TSH > stimulates hyperplasia > goiter

Question 23

iodine deficiency

Answer 23

low iodine content in soils in flooded areas, exposed to runoff etc

rich in seafood

Question 24

although T3 can promote anabolic and catabolic processes, the overall effect is

Answer 24

catabolic

Question 25

Hypothyroidism is characterized in part by elevated levels of TSH in circulation. Explain why this is the case.

Answer 25

Low thyroid levels > less negative feedback inhibition on pituitary gland > gland stimulates TSH to stimulate the thyroid gland to produce more thyroid hormones > thyroid hormones continue to be low, continuing this cycle of high TSH and low TH.

Question 26

What is the significance of having deiodinase enzymes being differentially expressed across tissue types?

Answer 26

Allows for tissue specific response for the same stimulus
fasting affects type 1 but not type 2 deiodinase, so T3 levels in the brain and pituitary still maintained during fasting