3. Physiology
        3.3. Endocrinology
3.3.4. Thyroid hormones

Thyroid hormones

T3 is more active

RT3 is inactive

T4 is secreted in greatest portion

T4 is converted into T3 in peripheral tissues

Synthesis

Metabolism of iodine

Daily intake = 500 microgram

Thyroid uptake = 120 microgram

Secretion as T3 and T4 from thyroid = 80 microgram

Diffusion from thyroid into ECF = 40 microgram

Liver and other tissue metabolise T3 and T4
* 60 microgram of iodine released back to ECF
* 20 microgram of iodine excreted as bile

Urine excretion = 480 microgram

 

Iodide (I-) uptake

Thyroid cell membrane facing the capillaries
--> Na-I Symporter
--> I- is transported into thyroid cells with secondary active transport
--> I- diffuses into collids

 

Thyroglobulin

 

Functions of thyroid cells

 

Synthesis of thyroid hormone

Enzyme:
Iodination (and maybe coupling) are catalyzed by thyroid peroxidase

Secretion

Thyroid cells ingest colloid by endocytosis
--> Protease in lysosome breaks the peptide bond between iodinated residues and thyroglobulin
--> MIT, DIT, T3 and T4 are liberated

T3 and T4 released

MIT and DIT broken down by iodotyrosine deiodinase

 

Metabolism

T3 and T4 are heavily bound to plasma proteins

Plasma proteins

NB:

--> Most of the circulating T4 are bound to TBG

 

T4

99.98% of T4 is bound

Free T4 is only 2ng/dL

Halflife = 6-7 days (long)

 

T3

99.8% of T3 is protein-bound
* 46% to TBG
* Rest to albumin

Free T3 = 0.15 microgram/dL

Halflife = shorter ????

 

Metabolism

T4 and T3 are deiodinated in the liver, kidney and other tissues

3 deiodinases

Some T4 and T3 are conjugated in liver to form sulfates and glucuronides
--> Secretion into bile and excreted

Some T4 and T3 pass directly from circulation into intestinal lumen

 

Fasting

T3 reduced by 10-20% in 24 hours of fasting

T3 reduced by about 50% in 3-7 days of fasting

--> Conservation of calories and protein

 

Actions and regulation

Mechanism of action

T3 and T4 binds to thyroid receptors in the nuclei
--> Hormone-receptor complex binds to DNA via zinc fingers

T3 binds to receptor more avidly

 

Actions

Main actions

Other actions

Calorigenic effect

 

Hypothyroidism

During development

Hypothyroidism during development causes

 

Hyperthyroidism

 

Regulation

Hypothalamus release
--> Thyrotropin-releasing hormone (TRH)

TRH stimulates anterior pituitary to release
--> Thyroid-stimulating hormone (TSH)

TSH stimulates release of T3 and T4 from thyroid

Negative feedback

T3 and T4 feeds back on anterior pituitary and hypothalamus to inhibit TSH and TRH formation
* T3 is the principle feedback

Secretion is inhibited before synthesis

Other factors

TSH inhibited by

TRH increased by cold and decreased by heat

 

TSH

Action of TSH

TSH receptor

Activates adenylyl cyclase via Gs protein

Other notes

Large doses of iodides act directly on thyroid
--> Mild and transient inhibition of organic binding of iodide
--> Inhibition of synthesis



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