Iodine metabolism and thyroid hormones

Question 1

the majority of iodine found in the body is stored in the …..

Answer 1

Thyroid gland (70-80%)

Question 2

In the foetus, iodine deficiency can result in [……], due to the important of [….] on development of organs.

Answer 2

spontaneous abortion, stillbirth, congenital abnormalities, perinatal mortality

thyroid hormone.

Question 3

In the children and adolescents, iodine deficiency can result in [….], due to important of […] in brain development.

Answer 3

impaired mental function, delayed physical development.

TH

Question 4

At any, iodine deficiency may result in development of goitre, hypothyroidism, and increased susceptibility of thyroid to radiation, cause by 2 possible mechanisms:

Answer 4

• aberrant negative feedback regulation of Hypothalamus, pituitary, thyroid axis.
• thyroid hormone synthesis and iodine uptake

Question 5

How does negative feedback work in the hypothalamus, pituitary, thyroid axis?

Answer 5

T4/T3 feedback inhibit the pituitary (short route) and hypothalamus (long route)

Question 6

thyroid hormone can only enter target cells that express these particular transporters….

Answer 6

monocarboxylate transporter MCT8 AND organic anion transporter OATP

Question 7

In the generation/delivery of thyroid hormone:

iodide (I-) enters the thyroid follicle (bordering the lumen) via the […..] symporter.

From the follicle, iodide travels through […] into the lumen of the thyroid follicle.

Follicular cells are responsible for synthesizing […] and secreting it into the lumen.

Just before reaching the lumen, Iodide is converted into the Iodine by the [….] enzyme on the apical interface of the follicle.

Iodine then reacts with tyrosine residues on
thyroglobulin (TG) via [….] reaction to form TG attached to [….].

A coupling reaction of MIT and DIT forms T3/T4 moieties in thyroglobulin (TG). Following this, the TG is brought back into the follicular cell by [….] process.

The TG/MIT/DIT molecule is taken up into lysosomes and broken down (proteolysed) into amino acid residues […..] and […].

T3 and T4 are released into the systemic circulation at the […..] membrane.

Answer 7

Na+/I- symporter.

Pendrin (anion transporter)

Thyroglobulin (precursor to thyroid hormone)

Thyroperoxide (TPO) enzyme

hydrogen peroxide (H2O2) reaction.
MIT and DIT (precursors to T3 and T4). (monoiodotyrosine  and diiodotyrosine.)

endocytosis process.

T3 and T4.

basolateral follicular cell membrane.

Question 8

[….] catalyzed the iodination of thyroglobulin into MIT or DIT.

Answer 8

thyroid peroxidase

Question 9

tyrosine residues on the thyroglobin molecule can be iodinated at two position on its […] ring. When iodinated at one position it becomes [….], at two positions it becomes [….]

Answer 9

benzene (position 3 and 5).

MIT
DIT

Question 10

the coupling of [….] creates T4/T3 depending on the combination.
DIT + DIT creates […]
MIT + DIT creates […]
[…] also catalyzes this coupling reaction.

Answer 10

iodotyrosines.

T4
T3

TPO (thyroid peroxidase)

Question 11

under normal circumstances, iodinated TG is only internalized into the follicular cell from the thyroid lumen upon stimulation by [….] for secretion. In the thyroid follicle it is digested in lysosome to form T3 and T4.

Answer 11

TSH

Question 12

in absence of stimulation by TSH, T3 and T4 moieties in TG are stored as [….]

Answer 12

colloid in thyroid lumen

Question 13

the bioavailability of thyroid hormones is governed by […] reactions

Answer 13

deiodination reactions via D1, D2, or D3.

Question 14

deiodination agents [….] serve to convert T4 to active T3 in the target tissue.

[….] create rT3 (revere T3) which acts to bind to an extranuclear TR —> [….].

Activate T3 is turned into inactive, rapidly degenerated T2 by action of [….] deiodination agent.

Answer 14

D1/D2

D1/D3
initiating actin polymerization in astrocytes.

D3.

Question 15

[…..] is a metabolite of TH degredation by decarboxylation (through D3). Via signalling through a g-protein coupled receptor, it acts to [….]

Answer 15

lower body temperature and reduce cardiac output.

Question 16

what are the physiological calorigenic actions of thyroid hormone? (4)

Answer 16

1. increase O2 consumption of all metabolically active tissue
2. increase energy substrate uptake and utilization.
3. increase energy consumption
4. increase cellular respiration rates

Question 17

what physiological effect does thyroid hormone have on the CV system?

increased production of Beta adrenergic receptors causes…..

Answer 17

increase pulse rate and heart weight (yes, weight not rate).
**weight increase related to increased transcription of structural and functional proteins in thermogenesis, mitochondrial function and muscle contraction.

makes tissues more responsive to inputs from sympathetic NS.

Question 18

how is transcription regulated by thyroid hormone receptor (THR)?

Answer 18

THR forms dimer with RXR and binds the TRE (thyroid responsive element) upstream of transcriptional start site.

The THR/RXR dimer bind to CoR co-repressor complex to initiate transcription of the target gene.

Binding of T3 to THR —> replacement of CoR with co-activator complex CoA –> initiates transcription of target gene.

NB: transcription process is dependant on T3 transactivation.

T3 binding of THR is also dependant on AF-2 ligand binding domain (not present in some THR’s).

Question 19

genomic action of thyroid hormone:

T3 binding to THR induces biosynthesis of co-activator, […]
—-> leads to […..] and [….]

Answer 19

PGC-1 alpha

mitogenesis and thermogenesis

NB:gene activation occurs over 6-24hrs

Question 20

the non-genomic action of TH are much [….] than genomic actions.

While[…] is most potent for genomic actions,
[..] is most potent for Non-Genomic actions.

Answer 20

faster.

T3.

T4.