MECHANISM OF

HORMONE
ACTION

INTRODUCTION
Hormones:
Chemical substances synthesized by one
type of cells & transported through blood
to act on another type of cells.

Endocrine

Paracrine
Autocrine

Insulin
GIT hormones
Prostaglandins

Functions

 Growth & Development.

ACTH,TSH,FSH,LH

Homeostatic control.
PTH- Ca, ADH- Water

Regulation of production,
use , storage of energy.
Insulin, Glucagon

Classificatio
n

 Polypeptide or Protein hormones

ACTH,Insulin,PTH
Water soluble, circulate freely, short half life
( 10-30 mins)
Bind to cell membrane receptors

Steroid hormones
Cortisol, Androgen, Estrogen
Hydrophobic, circulate with transport proteins,
half life (30-90 mins)
bind with intracellular receptor

Amines Amino acid derivatives

hormones
Thyroxine,catacholamine
Fatty acid hormones
Eg., prostaglandins

1.Cell surface receptors

Peptide hormones
Catecholamines

2.Intra cellular receptors

Steroid hormones
Thyroid hormones

Solubility
Transport
proteins
Plasma half
life

Group I
Lipophilic
Yes

Group II
Hydrophilic
No

Long

Short (minutes)

( hours to
days)
Receptor

Intracellular

Plasma
membrane

Mediator

Hormone
receptor
complex

cAMP, cGMP,
Ca2+, IP3, DAG,
Protein kinase

Examples.

Steroids,

Polypeptides,

HORMONE RECEPTORS
Hormone regulation molecules
Hormones mediates biological effect
by binding to specific receptors
Hormones receptors are proteins
Functional Domains of hormone
receptors
Recognition domain
Signal transduction domain

 Structure of Cell Surface

Receptor
Extracellular domains: ligandbinding domain.
Transmembrane domains
Cytoplasmic or intracellular
domains

G-protein coupled RECEPTORS

Characterised by the presence of
seven domains spanning the plasma
membrane
Transduce signals by altering the rate
of production of cAMP,
cGMP,IP3,DAG,Ca

Tyrosine Kinase RECEPTORS

Characterised by the presence of
seven domains spanning the plasma
membrane
Transduce signals by altering the rate
of production of cAMP,
cGMP,IP3,DAG,Ca

INSULIN RECEPTORS
Insulin receptors hetero tetra dimers (22)
Dimer is linked by multiple disulfide bonds
The extra-membrane -subunit binds with
insulin
The membrane spanning -subunit through
the tyrosine residue transduces the signal

STEROID HORMONE
RECEPTORS

Functional domains

Carboxy terminal binding with hormone

Adjacent DNA binding region
Two regions activate gene transcription
Two regions for the translocation of
receptors from the cytoplasm to nucleus
One region binds heat shock protein in the
absence of ligand

GROUP I HORMONES
Mechanism of action:
Through intracellular receptors gene
expression
Hormones lipophilic
Passive diffusion
In the cytoplasm binds with receptors
forming HRC

GROUP II HORMONES
Mechanism of action:
Through intracellular receptors gene
expression
Hormones lipophilic
Passive diffusion
In the cytoplasm binds with receptors
forming HRC

Group II hormone: mechanism of

action signal transduction

Second Messengers linked to G Protein

Second Messengers linked to G Protein

SYNTHESIS & DEGRADATION

OF cAMP

Hormones act through cAMP

Glucagon
, 2 Adrenergic Catecholamines
ACTH
TSH
LH
FSH
PTH

ADH
HCG
CRH
Calcitonin
MSH
Somatostatin

cGMP as second messenger

Guanylyl cyclase

GTP
cGMP
Several compounds (eg., Nitric oxide, ANP )
activate guanylyl cyclase which in turn
increase cGMP
cGMP as second messenger, avtivates
protein kinases & phosphorylates certain
enzymes
Phosphorylated enzymes causes smooth
muscle relaxation & vasodilation
cGMP also involved in rhodopsin visual cycle

SYNTHESIS & DEGRADATION

OF cGMP

Phosphatidyl inositol second

messenger system

IP3 and DAG

Phospholipid products can act as
second messengers
Phosphatidyl inositol 4,5 bisphosphate
is split into inositol trisphosphate (IP 3)
and diacylglycerol (DAG)
IP3 causes the release of Ca++ from the
ER
DAG goes on to activate protein kinase
C (PKC) along with the Ca++ - CaM
complex
PKC in turn phosphorylates protein
that go on to generate various cellular
effects

FORMATION OF IP3 & DAG

Calcium ions as second

messenger
Calcium ions can act as second
messengers
The non-stimulated cytoplasmic
calcium concentration is very low;
some stimulation events cause
transient elevation of intracellular
calcium
Calcium can bind proteins and
regulate cellular function as a result
One example of such calcium
protein binding is the calciumcalmodulin (CaM) complex

Ca++ Based Regulation

Hormones act through

Inositols or Ca

1-Adrenergic catecholamines
Acetylcholine (muscarinic)
Angiotensin II
Cholecystokinin
Gastrin
Gonadotropin-releasing hormone
Oxytocin
Platelet-derived growth factor (PDGF)
Substance P
Thyrotropin-releasing hormone
(TRH)

PROTEIN KINASE AS SECOND

MESSENGER
Binding of some hormones like
insulin to their respective membrane
receptors.
Activates a specific protein
kinase(tyrosine kinase).
Tyrosine kinase phosphorylates
tyrosine residue of specific proteins.
This brings about metabolic changes.

Hormones act through Protein

kinase

Insulin
Growth hormone (GH)
Prolactin
Insulin-like growth factors I and II
Chorionic somatomammotropin
Epidermal growth factor
Erythropoietin
Fibroblast growth factor (FGF)
Leptin
Nerve growth factor (NGF)
Platelet-derived growth factor
Adiponectin

Class

Mediator

Examples

Group I

Cytosolic
receptor

Hormone
receptor
complex

Corticoids,
Androgen
,Estrogen

Nuclear
receptor

Hormone
receptor
complex

Thyroid
hormones
Vitamin D

cAMP

Glucagon,Cate
cholamines,TS
H,ACTH,LH,FS
H,PTH

Group II
Cell
membrane
receptor

cGMP
Ca2+, IP3,

NO, ANP
TRH,

Hormones bind to cell surface

Receptors
a. Second messenger is cAMP
eg. Catecholamines
b. Second messenger is cGMP
eg. NO, ANP

c. Second messenger is Calcium or PI or

both
eg. TRH, GnRH

d. Second messenger is Protein kinase

eg. Insulin

Hormones bind to intracellular

Receptors
Two types
1) Cytosolic receptors
Eg., androgen, estrogen
2) Nuclear receptors
Eg., T3, T4

Protein Kinases
Protein kinases
phosphorylate
proteins i.e. they
add one or more
phosphates
The change in
charge at that site
makes major
changes in the
conformation,
affects activity
cAMP is inactivated
by
phosphodiesterases
, which quickly act
to downregulate its
activity

Action of cAMP Kinases on

Cells

Second Messengers linked to G

Protein
G-protein linked receptors are transmembrane proteins
that loop 7 times through the plasma membrane

G-protein consists of , & subunits

Receptor activates G protein, which binds GTP (-GTP)
When inactive, G protein is bound to GDP (-GDP)
G proteins interact with adenylyl cyclase, which makes
cAMP
Gs stimulates adenylyl cyclase
Gi inhibits adenylyl cyclase
When the hormone binds to a stimulatory receptor, the
G protein releases GDP and binds to GTP
Binding of the G protein to GTP enables it to activate
adenylyl cyclase

cAMP
Cyclic AMP is most common second messenger.
Hormones bind receptors and membrane-bound adenylyl
cyclase is activated via the G protein
Adenylyl cyclase catalyzes the conversion of ATP to cAMP
cAMP activates protein kinases
Protein kinases catalyze the phosphorylation of a specific
protein, which triggers a chain of reactions leading to the
particular metabolic effect of the hormone
Protein kinases are very specific in action
cAMP is rapidly inactivated and converted to AMP

GROUP I HORMONES MECHANISM

OF ACTION

1.
2.
3.
4.
5.
6.
7.

Steroid is secreted
Passes into cell
Into nucleus
Binds receptor, DNA
Activates or represses transcription
Controls translation
Peptide alters cellular activity

Ca++ Based Regulation

Calcium entry
can occur in
response to a
G-protein
stimulated
event
The calcium
may bind CaM
and activate a
protein kinase
that may go
on to regulate
other cellular
events