8-Thyroid hormones

Question 1

T4

Answer 1

Insoluble in serum
More than 99% protein bound
Binding proteins synthesised in the liver
10 times less effective than T3

Question 2

Thyroxine-binding globulin (TBG)

Answer 2

Binds 70-75% of plasma T4
A large circulating reservoir of T4
Prevents loss in urine
Single polypeptide chain
20% CHO by weight, molecular heterogeneity
Increased by T4 and by oestrogens/androgens
Stability and half-life are extended after T4 binding
Doubles in concentration during pregnancy
The level is lowered by corticosteroids, illness, stress, cirrhosis, nephrotic disorders
Prolongs T4 availability to target tissues

Question 3

Transthyretin (TTR)

Answer 3

Binds 20% of plasma T4
Important for delivery to CNS

Question 4

Albumin

Answer 4

Binds 5-10% of plasma T4

Question 5

Affinity and capacity

Answer 5

TBG has a high affinity and low capacity for T4
Transthyretin has a low affinity and high capacity for T4
Albumin has a very low affinity and high capacity for T4
TBG binds both T4 and T3; T½ = 5 days
Transthyretin binds T4 only; T½ = 2-3 days
Albumin binds T3 and T4; T½=15 days
Protein-bound T4:Protein bound T3 = 20:1

Question 6

Iodothryonine deiodinases

Answer 6

Seleno-cysteine containing enzymes
Selenium accepts iodide

Question 7

Transport of T3 and T4 into cells

Answer 7

Bound T3 and T4 cannot enter cells
Free T3 and T4 can enter cells via specific transporters (e.g. MCT8, MCT10, OATP1c1)
T3 is biologically active
T4 is INACTIVE and must be converted to T3 by intracellular iodothyronine deiodinases (DIO)

Question 8

Iodothronine deiodinase 1 (DIO1)

Answer 8

Predominates in liver, kidney and muscle.
Also found in the thyroid
Produces most of the circulating T3.

Question 9

Iodothryonine deiodinase 2 (DIO2)

Answer 9

Predominates in areas of the CNS and pituitary thryotropes.
Controls intracellular T3 concentration, only converts inside cells.
Important for feedback regulation
Found in skeletal muscle in some species.

Question 10

Iodothryonine deiodinase 3 (DIO3)

Answer 10

Produces inactive rT3
Prevents thyroid hormone access to specific tissues

Question 11

Thyroid hormone action

Answer 11

Thyroid hormone receptors (TR)
TRα and TRβ (THRA and THRB)
Found in nucleus
Heterodimer with retinoid X receptor (RXR)
Functions as a transcription factor
Binds to TRE
15-fold ↑ affinity for T3 than T4
Increased gene transcription
Can also inhibit gene transcription!
When T3 binds, corepressors are discharged and activators recruited

Question 12

Pituitary T3 responsive genes

Answer 12

Increase GH transcription
Decrease Prolactin and the alpha and beta subunits of TSH

Question 13

Hyperthyroidism

Answer 13

high metabolic rate
tremor
muscle wastage