Download Mechanism of hormone action Mechanism of hormone action

Mechanism of hormone
action
ผศ.ดร.พญ.สุวัฒณี คุปติวฒ
ุ ิ
ภาควิชาสรีรวิทยา
คณะแพทยศาสตรศิริราชพยาบาล
Aims
„
What is hormone receptor
„
Type of hormone receptors
- cell surface receptor
- intracellular receptor
„
Signaling via hormone receptors
„
Type of second messengers
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Hormone receptor
A protein of target cells that binds
to a specific hormone
Target cells: Any cells that have
specific receptor for hormone
Hormone and target cells specificity
H + R
HR complex
Specificity
Affinity
Number
Reversible
Single H + Different R
Different Effects
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Hormone action
action
Hormone
One hormone
Multiple actions
Blood
pressure
Gene
expression
Angiotensin II
Aldosterone
Signal
transduciton
Glucose
utilization
One actions
Multiple hormones
There are
are 22 groups
groups of
of hormone
hormone
There
receptors
receptors
Cell-surface receptors
Polypeptide hormones: GH, Insulin, GnRH, Gn
Catecholamines: E, NE
Intracellular receptors
Steroid hormone
Thyroid Hormone
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Cell
-surface receptors
Cell-surface
receptors
Glycoprotein that
that cross
cross the
the cell
cell membrane
membrane
Glycoprotein
to create
create extracellular
extracellular and
and intracellular
intracellular domains.
domains.
to
Extracellular domain
Intracellular domain
• Cell-surface receptors
G-protein coupled receptor
Receptor regulating ion channels
Receptor associated tyrosine kinase
Receptor containing tyrosine kinase
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• Cell-surface receptors
G-protein coupled receptor Receptor containing
tyrosine kinase
Receptor associated
tyrosine kinase
Extracellular
Cytoplasmic
PTH,LH, Glucagon
Receptor
Receptor regulating
ion channels
Insulin
Receptor
GH
Receptor
β-Adrenergic
Receptor
Three
Three stages
stages of
of cell
cell signaling
signaling
• Hormone recognition (1st messenger)
• Signal generation (2nd messenger)
• Alteration of intracellular processes
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G
G protein
protein couple
couple receptor
receptor
α subunit
protein
GG protein
Stimulator
bind to GDP
β, γ subunits
Inhibitor
Adenylyl cyclase
PLC
Ion channels
Adrenergic
G
G protein
protein couple
couple receptor
receptor
Movie
Hormone action mov
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Type
Type of
of G
G
alpha
alpha subunits
subunits
-
αi
Adenylyl cyclase
+ αS + αq + α 12,13
Adenylyl cyclase
PLC
Rho
Second Messengers
Messengers
Second
Chemical
Chemical signal
signal which
which connect
connect to
to other
other
protein
protein to
to co-ordinate
co-ordinate the
the activities
activities of
of
other
other molecule
molecule
G protein second messengers
Enzyme
Enzyme
Adenylyl cyclase
cAMP
Guanylyl cyclase
cGMP
Phospholipase C
Phospholipase A2
Ion channels
IP3, DAG
Arachidonic acids
Ca2+
2nd messenger
messenger
2nd
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Second Messengers
Messengers
Second
Amplification signals
signals
Amplification
Cellular responses
responses
Cellular
Signalamiplification.swf
cGMP Second Messenger
Guanylate cyclase
cGMP
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Action
Action of
of epinephrine
epinephrine on
on liver
liver cell
cell
Phospholipase CC
Phospholipase
Phospholipase CA2
Arachidonic acid
- PG
- TX
- Leu
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Receptor containing
containing tyrosine
tyrosine kinase
kinase
Receptor
Insulin Receptor
Receptor
auto-phosphorylation
Receptor Associated with Tyrosine Kinase
GH
Receptor
GH
GH
Plasma
membrane
JAK2
IGF
GH
JAK2
mRNA
P
GH
P
P
P
P
P
P
P
P
mRNA
JAK2 = Janus kinase (cytoplasmic tyrosine kinase)
STAT = Signal transducer and activators of transcription
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Intracellular
Intracellular Receptors
Receptors
NH2
DNA
Interact with other
binding
transcription factors
domain
Steroid
Receptors
COOH
Hormone
binding
Estrogen
Progesterone
Glucocorticoid
Thyroid hormone
Receptors
NH2
A/B
C D
E
DNA
Hormone
Binding
F COOH
Intracellular receptor
receptor model
model
Intracellular
Cytoplasmic receptor-thyroid
receptor-thyroid H,
H, vit
vit D,
D, aldosterone
aldosterone
Cytoplasmic
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Steroid
Steroid hormone
hormone
action
action
Pathway I: ER, PR, GR, AR
Basal
GTF
Gene
HRE
Stimulated
GTF
Gene
HRE
Hormone
Hormone
receptor
Co-activator
GTF
General transcription
factors
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Pathway II: thyroid hormone, vitamin D
repressor
Gene
HRE
Basal
GTF
Gene
HRE
GTF
Stimulated
Gene
HRE
RXR
Co-repressor
Hormone
Hormone receptor
Regulation of
of transcription
transcription by
by
Regulation
hormone not
not entering
entering cells
cells
hormone
CREB = cAMP response element binding protein
F = transcription factor = CREB-P
CRE = cAMP regulatory element
P = RNA polymerase
cAMP
CREB-P
CREB
Transcription
Protein
kinase A
Translation
or
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Two General Classes of Hormones
Steroid hormones
Slower
Slower
Peptide
Peptide hormones
hormones
Faster
Faster
Termination of hormone action
Peptide hormones
• Hormones are degrade by blood enzymes
• Plasma membrane-hormone-receptor complex
was internalized by endocytosis and degraded
by lysosomal enzymes
Steroid hormones
• In the absence of further stimulation, newly
synthesized RNA and proteins are degraded by
cytoplasmic enzyme actions
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Practice Questions
Which of the following is a steroid
hormone?
A. Insulin
B. Testosterone
C. Epinephrine
D. Oxytocin
E. Growth hormone
Ans:
Ans: B
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The transcription of new messenger RNA
is a function of
A. steroid hormones.
B. amino acid-based hormones.
C. pancreatic hormones.
D. catecholamines.
E. pituitary gland hormones.
Ans:
Ans: A
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