Mekanisme Kerja Hormon

dr. Susila Sastri M.BiomedBiokimia FK-Unand

Hormone

Struktur Kimia Hormon

1. Polipeptida• Insulin• Glucagon

2. Derivat asam amino (amin)• Epineprin• Serotonin• Tyroxin

3. Steroid (derivat kolesterol)• Aldosteron• Cortisol• Retinoic acid

4. Eicosanoid (polyunsaturated • acid, (20atom C)

• Prostadglandin E• Thromboxane A2

Simple Intracellular & Extracelluler Signaling

Hormon Action

Hypophise Anterior

Neurohormone

　　

GAS MOLECULE

Cell Communication

Second messenger:

Small molecules synthesized in cells in response to an external signal are the second messengers, which are responsible for intracellular signal transduction:

Ca2+, DG, Cer, IP3, cAMP, cGMP

Receptor Receptors: specific membrane proteins,

which are able to recognize and bind to corresponding ligand molecules, become activated, and transduce signal to next signaling molecules:

A. Membran

B. Intra Sel

Glycoprotein or Lipoprotein

HypothalamusAnterior pituitary Posterior pituitary

Thyrotropin

ACTH

Somatotropin

LH

FSHProlactin

Vasopressin

Oxytocin

ThyroidAdrenalCortex

AdrenalMedullaPancreas Ovary Testis

Muscles liver Tissues

Liver,muscles

Estradiol TestosteroneInsulin,glucagon,somatostatin

T3 Cortisolaldosterone

Mammary glands

Reproductive organs

Epinephrine

Releasinghormones

Nervous

Kelenjer-Hormon-Target Sel

1. Membrane receptors

Signal transduction mediated by membrane receptor

• cAMP dependent-protein kinase A pathway

• cGMP dependent PKG pathway 　• Ca2+ dependent PK pathway 　• Tyrosine protein Kinase pathway

• NF-κB pathway 　• TGF- βpathway

Membrane Receptor

Cyclic AMP

　 Mekanisme Signal Tranduksi

Glucagon

Cyclic AMP Cyclic GMP Ca2+ Diacylgycerol Proteinsubstrates

PK-A PK-G Calmodulin PK-C Protein Ser/Thr kinases

Protein substrates

Protein substrates

Protein substratesMultifunctional kinases

Otherphospholipases

1 2 3 4 5

11 2 3 4 5

Tyrosine kinase

IP3G G G G

Insulin T-cellActivation

Nitricoxide

G protein

End result is phosphorylation ofone or more proteins

Hormon-2nd Massengger- Enzim

Inositol triphosphate System

PLC; phospholipase CPIP2: phosphoinositolDAG:diacylgliserolIP3:inositol triphosphatPKC: phosphokinase C

Intracellular receptor (DNA transcription regulated

receptor)

Steroid Hormone, VD3, Thyroxine

• Cytosolic R: glycocorticosteroid H

• Nuclear R: thyroxine, estrogen, androgen, progesterone

Hormon - Receptor

• highly specificity

• highly affinity

• saturation

• reversible binding

• special function model

Control of receptor activity

• Phosphorylation or dephosphorylation of R

• Phospholipid of membrane

• Enzyme catalyzed hydrolysis

• G protein regulation

Thyroid Mechanism of Action

Adrenaline Mechanism of action

ACTH Mechanism of Action

Aldosteron Mechanism of Action

Estrogen Mechanism of Action

Androgen Mechanism of Action

Insulin Receptor

Insulin Action

Glucagon

GH/ STH

hormons: glucagon, epinephrine

inactive AC active AC

ATP cAMP

inactive PKA active PKA

phosphorylase b kinase

phosphorylase b kinase

P

ATP

ADP

H2O

Pi

phosphorylase b

P

P

ATP ADP

Pi

H2OATP ADP

glycogen synthase

glycogen synthase

P

H2OPi protein phosphatase-1

(active) (inactive)

inhibitor-1 (active)

inhibitor-1 (inactive)

phosphorylase a

ATP