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Mechanism of hormone action
Mechanism of hormone Mechanism of hormone actionaction
ผศ.ดร.พญ.สุวัฒณี คุปติวฒิุ
ภาควิชาสรีรวิทยา
คณะแพทยศาสตรศิริราชพยาบาล
AimsAimsWhat is hormone receptorhormone receptor
Type of hormone receptorshormone receptors
-- cell surface receptorcell surface receptor
-- intracellular receptorintracellular receptor
SignalingSignaling via hormone receptorsvia hormone receptors
TypeType of of second messengerssecond messengers
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A protein of target cells that binds
to a specific hormone
HormoneHormone receptorreceptor
Target cells: Any cells that have
specific receptor for hormone
HormoneHormone and target cells specificityand target cells specificity
SpecificitySpecificity
H + R HR complexHR complex
AffinityAffinityNumberNumber
ReversibleReversible
Single H Different R Different Effects+
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Hormone actionHormoneHormone actionaction
One hormoneOne hormone
Multiple actionsMultiple actions
One actionsOne actions
Multiple hormonesMultiple hormones
Gene expression
Signal transduciton
Glucose utilization
Blood pressure
AldosteroneAngiotensin II
There are 2 groups of hormone receptors
There are 2 groups of hormone There are 2 groups of hormone receptorsreceptors
CCellell--surface receptorssurface receptors
Intracellular receptorsIntracellular receptors
Polypeptide hormones: GH, Insulin, GnRH, Gn
Catecholamines: E, NE
Steroid hormone
Thyroid Hormone
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Cell-surface receptorsCellCell--surface receptorssurface receptors
Glycoprotein that cross the cell membrane
to create extracellular and intracellular domains. Glycoprotein that cross the cell membrane
to create extracellular and intracellular domains.
Extracellular domain
Intracellular domain
•• CellCell--surface receptorssurface receptors
G-protein coupled receptor
Receptor regulating ion channels
Receptor containing tyrosine kinase
Receptor associated tyrosine kinase
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GHReceptor
Receptor associated tyrosine kinase
β-Adrenergic Receptor
G-protein coupled receptor
Receptor regulating ion channels Insulin
Receptor
Receptor containing tyrosine kinase
•• CellCell--surface receptorssurface receptors
Extracellular
CytoplasmicPTH,LH, Glucagon
Receptor
Three stages of cell signalingThree stages of cell signaling• Hormone recognition (1st messenger)• Signal generation (2nd messenger)• Alteration of intracellular processes
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G protein couple receptorG protein couple receptor
G proteinG proteinG protein
α α subunitsubunit
β, γ β, γ subunitssubunits
StimulatorStimulatorbind to GDPbind to GDP
InhibitorInhibitor
AdenylylAdenylyl cyclasecyclasePLCPLCIon channelsIon channels
AdrenergicAdrenergic
G protein couple receptorG protein couple receptor
MovieMovieHormone action Hormone action movmov
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Type of G alpha subunits
Type of G alpha subunits
ααii ααSS ααqq α α 12,1312,13
AdenylylAdenylyl cyclasecyclaseAdenylylAdenylyl cyclasecyclase PLCPLC RhoRho
++ ++ ++--
Second MessengersSecond Messengers
Chemical signal which connect to other
protein to co-ordinate the activities of
other molecule
Chemical signal which connect to other
protein to co-ordinate the activities of
other molecule
G protein second messengersAdenylyl cyclase
Guanylyl cyclasePhospholipase C
Ion channels
cAMPcGMPIP3, DAG
2nd messenger2nd messengerEnzymeEnzyme
Ca2+Phospholipase A2 Arachidonic acids
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Second MessengersSecond Messengers
Amplification signalsAmplification signals Cellular responsesCellular responses
Signalamiplification.swf
cGMP Second Messenger
Guanylate cyclase
cGMP
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Action of epinephrine on liver cellAction of epinephrine on liver cell
CPhospholipase A2
Arachidonic acid- PG- TX- Leu
Phospholipase CPhospholipase C
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Receptor containing tyrosine kinaseReceptor containing tyrosine Receptor containing tyrosine kinasekinase
Receptorauto-phosphorylation
Insulin Receptor
GH GH GH GH
P PPP P
P
P
PP
JAK2 JAK2
mRNA
mRNA
IGF
GHReceptor
Plasmamembrane
Receptor Associated with Tyrosine Kinase
STAT = Signal transducer and activators of transcription JAK2 = Janus kinase (cytoplasmic tyrosine kinase)
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Intracellular ReceptorsIntracellular ReceptorsIntracellular Receptors
Steroid Receptors
Thyroid hormone Receptors
Estrogen
Progesterone
Glucocorticoid
DNA HormoneBinding
NH2COOHA/B C D E F
Interact with othertranscription factors
DNAbinding
domain
Hormonebinding
NH2 COOH
Intracellular receptor modelCytoplasmic receptor-thyroid H, vit D, aldosterone
Intracellular receptor modelCytoplasmic receptor-thyroid H, vit D, aldosterone
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Steroid hormone actionSteroid hormone Steroid hormone actionaction
HRE GeneGeneGTF
Pathway I: ER, PR, GR, ARPathway I: ER, PR, GR, AR
HRE GeneGeneGTF
Basal
Stimulated
Hormone
Hormone receptor
Co-activator
GTF General transcriptionfactors
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Pathway II: thyroid hormone, vitamin DPathway II: thyroid hormone, vitamin D
HRE GeneGene
repressor
HRE GeneGeneGTF
Basal
HRE GeneGene
GTF Stimulated
Co-repressorRXR Hormone
Hormone receptor
Regulation of transcription by hormone not entering cellsRegulation of transcription by hormone not entering cells
Proteinkinase A
Transcription
Translation
cAMP
CRE = cAMP regulatory element
CREB = cAMP response element binding protein
CREB-P
or
P = RNA polymerase
CREB
F = transcription factor = CREB-P
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Peptide hormonesPeptide hormones
Two General Classes of HormonesSteroid hormonesSteroid hormones
Peptide hormonesPeptide hormones
SlowerSlower
FasterFaster
Termination of hormone actionPeptide hormonesPeptide hormones
•• Hormones are degrade by blood enzymesHormones are degrade by blood enzymes
•• Plasma membrane-hormone-receptor complex was internalized by endocytosis and degraded by lysosomal enzymes
Steroid hormonesSteroid 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. InsulinB. TestosteroneC. EpinephrineD. OxytocinE. Growth hormone
AnsAns: B: B