Mechanism of Action & Functions of Thyroid Hormone I Endocrine Physiology
This video will discuss about the following:
1. Mechanism of action of thyroid hormone
2. Functions of thyroid hormone
3. Calorigenic effect
4. Effect on cardiovascular system
5. Effect on nervous system
6. Effect on cholesterol metabolism
You can also watch the YouTube video of same on HM Learnings YouTube channel
4. Calorigenic effect (↑ BMR)
• Thyroid hormone increase the energy consumption and O2
consumption due to its calorigenic actions.
• It stimulates futile cycles where energy is consumed but without
any useful work.
• It has this effect by its action of Na+-K+ pump, thermogenesis and
metabolism.
5. Na+-K+ pump
• T3 increase the synthesis of new transporter (Na+-K+ pump) that
are inserted into the plasma membrane (stimulation of
transcription of alpha and beta subunits of pump)
• T3 leads to stabilization of mRNA that encodes for Na+-K+ pump.
• Increased Na+-K+ pump activity is compensated by leaky channels
of Na+ and K+.
• Thus energy which is consumed by Na+-K+ ATPase is a wastage.
6. Effects on metabolism
Carbohydrate metabolism
• Increase the rate of carbohydrate absorption from intestine
• Increase hepatic rate of production of glucose (gluconeogenesis) via increase in
expression of key gluconeogenic enzymes (phosphoenol pyruvate carboxykinase,
pyruvate carboxylase, glucose-6-phosphatase )
Protein metabolism
• Both proteolytic and proteogenic effect, but proteolytic effect is predominate.
• Products of proteolysis (amino acid) are made available for gluconeogenesis.
Fat metabolism
• Both lipolytic and lipogenesis effect, but lipolytic effect is predominant.
• In adipose tissue, triglyceride are hydrolyzed to fatty acids and glycerol. Fatty
acids will be fuel for energy and glycerol act as substate for gluconeogenesis.
Thus there is increase in energy and O2 consumption
7. Thermogenesis (Non-shivering)
• T3 stimulates non-shivering thermogenesis by uncoupling oxidative
phosphorylation from ATP generation.
• E.g. Brown fat present in newborn (upper back, neck) have abundant
mitochondria. UCP1 (aka thermogenin) is present on inner
mitochondrial membrane.
• It is a H+ channel.
• In response to T3 stimulation, it opens and allow H+ ion to move from
intramembrane space (high concentration) to matrix (low
concentration) of mitochondria and hence dissipates the proton
gradient required for ATP generation.
• Thus , energy is liberated as heat instead of ATP.
8. Effect on Cardiovascular system
• T3 increase the expression of B adrenergic receptors on heart as
well as their response to circulating catecholamines.
• Apart from these, T3 enhance the expression of genes for alpha-
myosin heavy chain, SERCA, G proteins, Na K ATPase and K+
channels.
• T3 inhibits the expression of genes for beta myosin heavy chain,
phospholamban, two types of adenylyl cyclase and NCX.
• The net result is increased heart rate and force of contraction.
• Increase in cardiac output
9. Effect on Nervous system
• Synapse formation and brain development
• Cretinism- profound mental retardation, short statue, delay in
motor development, coarse hair and a protuberant abdomen. It
occurs due to thyroid deficiency during pregnancy.
Effect on Cholesterol metabolism
• Decrease in circulating levels of cholesterol because of increase of
LDL receptors on liver.
