thyroid hormones - notes

Question 1

MCT8

Answer 1

transporter of thyroid hormone into cells
mutation results in impairments in neurological development and thyroid function
part of monocarboxylate (MCT) protein family

Question 2

effects of TRs when no ligand present

Answer 2

can have opposite effect is no thyroid hormone present
so if the TR activates transcription of a certain protein when TR is activated by hormone, then when hormone is not present can inhibit transcription of that gene

Question 3

auto-regulation of synthesis and secretion of TH

Answer 3

sudden increase in iodide (such as after intake of KI or seaweed) results in decrease in iodide uptake and organification
exact mechanism not clear
due in part to suppressive effect of iodide on NIS and on the peroxidation system essential for tyrosine iodination
sudden high level will also suppress release of T4 and T3 and decrease total blood content in thyroid
all temporary effects!

Question 4

mechanism of TRH action

Answer 4

via phosphatidylinositol 4,5 bisphosphate second messenger system

note that TRH is rapidly inactivated by plasma enzymes so that its concentration in the peripheral circulation is very low

Question 5

binding of T3 and T4 to plasma proteins

Answer 5

T4 binds to TBG, thyroxine-binding prealbumin (TBPA), and albumin with ratio of 60:30:10
T3 only binds to TBG and albumin
T4 remains bound for about 9 days
T3 remains bound for about 1 day

Question 6

types of deiodinase

Answer 6

three types:
D1 and D2 are both outer-ring or 5’-deiodinating enzymes
D1 in liver, kidney and thyroid - responsible for production from T4 of some of the circulating T3
D2 in pituitary, CNS and brown fat - responsible for local generation of T3 from T4 in these tissues
D3 inner ring or 5-monodeiodinating enzyme, converts T4 to T3 and rT3 and 3,3’-T2 (T3’s inactive derivative) - in placenta and pregnant uterus and at lower levels in other tissues, especially the brain, during development
differential expression of these enzymes in different tissues allows for level of hormone appropriate for that tissue to be sensed even though tissues are all exposed to the same amount of circulating hormone