Download Hormone Actions

Hormone Actions
2-May-17
Hormone actions
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Hormone Receptors

Hormones produce their effects by


Combining with specific receptors
The 1st step of hormone action


Binding to receptor at the target cell
Receptors can be located
1.
2.
3.
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On target cell membrane
In the cytoplasm
In the nucleus
Hormone actions
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Hormone Receptors

When hormone reacts with receptor


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Initiate a cascade of reactions in the cells
With each stage becoming more powerful
Thus even small conc of hormone
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Can have a large effect
Hormone actions
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Hormone Receptors

Hormone receptors


Are large protein
Each cell that is to be stimulated


Has large number of receptors (2000 – 200,000)
Each receptor (type)


Highly specific for a single hormone
Target tissue that are affected
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Are those that have the receptor
Hormone actions
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Hormone Receptors

i.
Location of different type of hormone
receptors
In or on surface of cell membrane
a.
b.
ii.
Protein & peptide hormone
Catecholamine
In the cell cytoplasm
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Steroid hormone
Hormone actions
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Hormone Receptors
iii.
In the nucleus
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Thyroid hormones
Hormone actions
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Regulation of Numbers of
Receptor

Number of receptor in target cell


Does not remain constant
Receptor protein can be
1.
2.
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Destroyed or inactivated
Activated or new proteins can be formed
Hormone actions
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Regulation of Numbers of
Receptor

In most cases, the binding of hormone to
receptor on target cell

 Number of active receptors
1.
2.

This is known as “down-regulation”
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Due to inactivation or
 Production of new receptors
Cause  in responsiveness of target tissue to the
hormone
Hormone actions
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Regulation of Numbers of
Receptor

However, some hormone


Can cause “up-regulation” of receptors
Stimulating hormone

Induces formation of new receptor


The target tissue becomes progressively
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 Protein synthesis on target tissue
More sensitive to the stimulating hormone
Hormone actions
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A. Intracellular Signaling


Generally
Binding of hormone to receptor



Hormone – receptor complex
Alter the function of receptor
Activated receptor
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Initiate the hormone effect
Hormone actions
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Intracellular Signaling
1.

Change in membrane permeability
Neurotransmitter substance

Acetylcholine, nor epinephrine
Combine with receptors on post synaptic
membrane
 Change the structure of receptor
 Open or close ionic channels
 Movement of ions
 Subsequent effect on post synaptic cell

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Hormone actions
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Intracellular Signaling

Circulating hormones

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Nor epinephrine & epinephrine
Have similar effect of
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Opening or closing ionic channels
Hormone actions
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Intracellular Signaling
2.

Activation of intracellular enzymes
Hormone receptor complex

Activate or inactivate enzymes
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Immediately inside the cell membrane
Hormone actions
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Intracellular Signaling

Insulin

Bind to receptor portion that protrudes
outside the membrane


Cause structural change in receptor molecule
Causes the portion of receptor that
protrude inside the cell
To become activated kinase
 Promote phosphorylation of different
substances

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Hormone actions
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Mechanism of Action of Insulin
Insulin
Glucose
S
S
S
S
Tyrosine
kinase
Glucose
Protein synthesis
fat synthesis
glucose synthesis
growth & gene
expression
Phosphorylase
enzyme
Glucose
transporters
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Hormone actions
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B. Second Messenger

Some hormone



Cannot penetrate cell membrane easily
Interact with receptor on the exterior
Coupling of receptor to intracellular
enzyme machinery

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Results in generation of an intracellular signal
or message
Known as “second messenger”
Hormone actions
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1.Cyclic AMP Second
Messenger
Hormone

Receptor
Adenyl
cyclase
Gs protein
ATP
cAMP
Prot. Kinase-A
Phosphorylated Prot.

Hormone bind to
receptor on cell
surface
Hormone – receptor
complex


Biological effect
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Hormone actions
Activate Gs protein
Gs protein activates
adenyl cyclase
enzyme
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Cyclic AMP Second Messenger
Hormone

Receptor
Adenyl
cyclase
Gs protein
Activated adenyl
cyclase

ATP
cAMP

Prot. Kinase-A
Phosphorylated Prot.

Biological effect
2-May-17
Catalyze the
conversion of ATP 
cAMP
cAMP activate
protein kinase-A
which
Hormone actions
Catalyzes the
phosphorylation of
proteins
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Cyclic AMP Second Messenger
Hormone

Receptor
Adenyl
cyclase
Gs protein
The phosphorylated
proteins

ATP
Produce the various
physiologic effects
cAMP
Prot. Kinase-A
Phosphorylated Prot.
Biological effect
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Hormone actions
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2.Phospholipase-C Second
Messenger
Hormone

Phospholipase-C
Receptor
PIP2
PLC
Hormone bind to
receptor

DAG
Gs protein

Prot kinase-C
IP3
Endoplasmic
reticulum

Phosphorylated
prot
Ca++
Cell response
2-May-17
Physiologic
effect
Hormone actions
Hormone-receptor
complex
Activate G protein
The G protein
activate
phospholipase-C
(PLC)
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Phospholipase-C Second
Messenger
Hormone

Phospholipase-C
Receptor
PIP2
PLC
The phospholipase-C
(PLC)

DAG
Gs protein
Prot kinase-C
Catalyze breakdown
of phospholipids in
cell membrane
IP3
Endoplasmic
reticulum
Phosphorylated
prot
Ca++
Cell response
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Physiologic
effect
Hormone actions
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Phospholipase-C Second
Messenger
Hormone

Phospholipase-C
Receptor
PIP2
PLC
DAG
Phosphatidylinositol
biphosphate (PIP2)
converted into

Gs protein
Prot kinase-C
IP3
Endoplasmic
reticulum

Phosphorylated
prot
Inositol triphosphate
(IP3) and
Diacylglycerol
(DAG)
Ca++
Cell response
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Physiologic
effect
Hormone actions
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Phospholipase-C Second
Messenger

Hormone
Phospholipase-C
Receptor
Inositol triphosphate
(IP3)
PIP2
PLC

DAG
Gs protein
Prot kinase-C
IP3
Endoplasmic
reticulum
Phosphorylated
prot
Ca++
Cell response
2-May-17



Physiologic
effect
Hormone actions
Mobilize Ca++ from
endoplasmic
reticulum (ER)
 intracellular Ca++
conc
Cell response
Diacylglycerol
(DAG)
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Phospholipase-C Second
Messenger
Hormone

Phospholipase-C
Receptor
Diacylglycerol (DAG)

PIP2
PLC
DAG
Gs protein

Prot kinase-C
IP3
Endoplasmic
reticulum
Phosphorylated
prot
Ca++
Cell response
2-May-17
Activate protein
kinase-C (PKC)
which

Phosphorylates large
number of protein
Leading to cell
response
Physiologic
effect
Hormone actions
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3.Ca++ - Calmodulin Second
Messenger
Ca++

Ca++ channel
Ca++ entry into the
cell by

 conc
Ca++
Ca++
Ca++ Calmodulin
complex


Hormone actions
Open Ca++ channels
Hormone interact
with membrane
receptor

Initiates physiologic
effect
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Change in
membrane
membrane pot
Open Ca++ channels
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Ca++ - Calmodulin Second
Messenger
Ca++

Ca++ channel
On entering the cell


 conc
Ca++
Ca++
Ca++ Calmodulin
complex
Ca++ bind to
calmodulin
The Ca++ calmodulin complex

Activate
calmodulin –
dependent - kinases

Initiates physiologic
effect
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Hormone actions
Initiate multiple
effects
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Regulation of Gene Expression
Hormone

H-R
complex
H-R
complex

Hormone cause 
protein synthesis in
target cells
Protein then act as

R
Ribosome
DNA


mRNA
Enzymes
Transport proteins
Structural proteins
prot synthesis
Nucleus
Response
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Hormone actions
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Regulation of Gene Expression
Hormone

H-R
complex
H-R
complex
Hormones that act
by this mechanism
include


R
Ribosome

DNA
mRNA
prot synthesis
Steroids
Thyroid hormones
1,25
dihydrocholecalcife
rol
Nucleus
Response
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Hormone actions
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Regulation of Gene Expression
Hormone

H-R
complex
H-R
complex

R
Ribosome
DNA
Hormone enter
cytoplasm where
either
Bind to specific
receptor

mRNA
prot synthesis
Transformation of
receptor

Nucleus
Expose DNA
binding domain
Response
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Hormone actions
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Regulation of Gene Expression
Hormone

H-R
complex
Receptor-hormone
complex

H-R
complex

Or some hormones

R
Ribosome
DNA

mRNA
prot synthesis
Nucleus
Moves to DNA
Enter cytoplasm
and into the
nucleus
Then bind to
receptor found in
the nucleus
Response
2-May-17
Hormone actions
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Regulation of Gene Expression
Hormone

H-R
complex
To form Receptorhormone complex

H-R
complex

R
Ribosome
DNA
mRNA
prot synthesis
The binding of
receptor-hormone
complex to DNA

Nucleus
Which moves to
DNA
 transcription of
mRNAs
Response
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Hormone actions
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Regulation of Gene Expression
Hormone

H-R
complex
H-R
complex
mRNAs are then
translated in
ribosomes

R
Ribosome

DNA
Production of
protein
Alters cell function
mRNA
prot synthesis
Nucleus
Response
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Hormone actions
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Regulation of Gene Expression
Hormone

H-R
complex

H-R
complex

R
Ribosome
DNA

prot synthesis
Nucleus
Response
Hormone actions
Bind hormone in the
nucleus
Glucocorticoids
receprors

mRNA
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Estrogen,
triiodothyronine
receptors
Located in cytoplasm
But migrate into
nucleus as soon as it
binds to hormone
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