Mechanism of Action of Thyroid Hormone

Mechanism of action of lipid soluble(steroid) hormones.
Lipid soluble hormones enters the cell cause

synthesis of proteins in the target cell. These proteins are presumably the enzymes which, in turn, activate
other functions of the
cells.
1. The steroidal hormone enters the cytoplasm of the target cell where it binds with a specific, high- affinity
receptor protein.
2. The receptor protein- hormone complex, so formed, then diffuses into (or is transported into) the nucleus,
where it reacts with the nuclear chromatin.
3. Somewhere along this route, the receptor protein is structurally altered to form a smaller protein with low
molecular weight. Or else the steroid hormone is transferred to a second smaller protein.
4. The combination of the small protein and hormone is now the active factor that stimulates the specific
genes to form messenger RNA (mRNA) in the nucleus.
5. The mRNA diffuses into the cytoplasm where it accelerates the translation process at the
ribosomes to synthesize new proteins.
Example, the aldosterone, one of the mineralocorticoids secreted by adrenal cortex, enters the cytoplasm of
the renal tubular cells. These tubular cells contain its specific receptor protein and hence above sequence of
events follows. After about 45 minutes, the proteins begin to appear in the renal tubular cells that promote
sodium reabsorption from the tubules and potassium secretion into the tubules. This characteristic delay, of
about 45 minutes, in the final action of this steroid hormone is in marked contrast to the almost
instantaneous action of some of the peptide hormones.
Mechanism of action of thyroid hormone:
The mechanism of action of thyroid hormones is similar to that of steroid hormones. They act by
binding with the intracellular receptors. With few exceptions like adult brain and gonads, receptors
for thyroid hormones are present in all tissues and organs. Though the developing neurons in
infants and children are highly sensitive to thyroid hormones, it is not clear why the adult neurons
are not so sensitive.
The steps of mechanism of action are as follows:
1. T3 and T 4 enter the cells of the target organs by carrier mediated (energy dependant) transport.
2. lnside the cell, most of the T4 is converted to T3, which then binds with the thyroid-hormone
receptors (TR) present on nucleus. The thyroid receptor protein is bound to thyroid-hormone
response elements (TRE) in the DNA via Zinc fingers.
3. Binding of T3 with thyroid hormone receptor-TRE elements causes translation of DNA that in
turn increases the transcription of mRNA .
4. Increased mRNA causes increased intracellular protein synthesis that stimulates cellular growth
and maturation, increases intracellular enzyme synthesis, increases mitochondria formation and
respiratory enzyme synthesis, and increases Na+-K+ATPase activity.The increased Na+-K+ATPase
activity increases cellular oxygen consumption and increased mitochondrial activity increases
general metabolism of the cell.
Mechanism of action of insulin
Insulin acts on insulin receptors present on various cells.The major target tissues of insulin are
liver, skeletal muscle and adipose tissues.
Insulin Receptor
Insulin receptor (IR) is a glycoprotein tetramer consisting of two and two , subunits. The
subunits are present on the membrane extracellularly, whereas the subunits traverse the
membrane. Thus, subunits have extracellular domain, membrane domain, and intracellular
domain . The and , subunits are glycosylated. They are bound to each other by disulfide bridges.
Steps
Insulin binding to its receptors trigger following events:

1. The binding of insulin to subunits brings about conformational change in the subunits.
2. The intracellular domain of subunits possesses tyrosine kinase activity. Conformational change
of the subunits activates its tyrosine kinase activity. This produces autophosphorylation of
subunits on tyrosine residues.
3.Autophosphorylation triggers phosphorylation of many intracellular proteins that alter cell

functions. Dephosphorylation of proteins also occurs.
4.The active tyrosine kinase phosphorylates tyrosines on insulin receptor substrates (IRS 1 and
IRS2). IRS proteins are docking proteins to which a variety of downstream proteins bind. Thus
IRSphophotyrosines serve as docking site and activating site for different protein kinases and
protein phosphatases . The IRS also serves as facilitatory proteins that link to membrane G proteins,
phospholipases, and ion channels.
5.Phosphorylation of IRS causes activation or deactivation of many target enzymes, translocation of

GLUTs (glucose transport proteins) to the cell membranes and induction or suppression of genes in
the nucleus. This results in synthesis of different intracellular proteins.
6.GLUT 4 move to the cell membrane facilitates glucose entry into the cell. The insertion of
different protein channels on the plasma membrane increases entry of amino acids, potassium,
magnesium, and into the cell. Activation of mitogenic proteins Increases transcription of various
factors that are essential for stimulation of gene expression, especially concerned with cell growth.
When epinephrine stimulates its target organs. it must first bind to adrenergic receptor proteins in
the plasma membrane of its target cells. There are two types of adrenergic receptorsalpha and
beta. Stimulation of the beta-adrenergic receptors by epinephrine results in activation of adenylate
cyclase and the production of Cyclic AMP.
Stimulation of alpha-adrenergic receptors by epinephrine, in contrast activate the target cell via the
Calcium second-messenger system .The binding of epinephrine to its alpha-adrenergic receptor
activates, via G-proteins, an enzyme in the plasma membrane known as phospholipase C . The
substrate of this enzyme, a particular membrane phospholipid is Split by the active enzyme into
inositol triphosphate[IP3] and another derivative, diacylglycerol . Both derivatives serve as second
messengers.
The IP3, leaves the plasma membrane and diffuses through the cytoplasm to the endoplasmic
reticulum. The membrane of the endoplasmic reticulum contains receptor proteins for lP3.This
binding of IP3 to its receptors causes specic Ca channels to open. so that Ca diffuses out of the
endoplasmic reticulum and into the cytoplasm .
As a result of these events. there is a rapid and transient rise in the cytoplasmic Ca+ concentration.
This signal is amplified by the opening of Ca+ channels in the plasma membrane. This may be due to
the action of a messenger sent from the endoplasmic reticulum to the plasma membrane. The Ca
promotes the hormonal effect in the target cell.

Mechanism of Action of Thyroid Hormone

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Mechanism of action of lipid soluble(steroid) hormones.

Lipid soluble hormones enters the cell cause

The steps of mechanism of action are as follows:

Mechanism of action of insulin

Insulin binding to its receptors trigger following events:

3.Autophosphorylation triggers phosphorylation of many intracellular proteins that alter cell

5.Phosphorylation of IRS causes activation or deactivation of many target enzymes, translocation of

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