HORMONE SYNTHESIS,

RELEASE AND TRANSPORT

Intercelluler Communication
 All cells detect and respond to
environmental stimuli
Intracelluler communication :
- endocrine
- nervous
- immune
 Endocrine glands secrete hormones

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 Hormone
 Hormone:
produced in small amounts by specific
tissues (endocrine glands), control the
metabolic and biological activities in the
target cells
 HORMONE CLASSIFICATION

 Protein and polypeptide

 Amine
 Steroid
 Eicosanoid
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 PEPTIDE HORMONES

 Consist of specific amino acids

 Synthesized as large precursor proteins
 Stored in membrane-enclosed
compartments
 Hydrophillic
Protein and Polypeptide Hormones Synthesis

: Peptide hormone synthesis and packaging

Proinsulin

Insulin
AMINE HORMONES

 Derived from the amino acid tyrosine

 Includes thyroid hormones and
catecholamines
 Stored until secreted
 Thyroid Hormones

 Thyroid gland produce T3 and T4

hormones
 Iodide (I-) actively transported into the
follicle of thyroid gland
 Oxidized to iodine (Io) by a peroxidase
 STEROID HORMONES

 Precursor: Cholesterol
 Lipophillic
 Immediately released from the cell
following synthesis
EICOSANOIDS HORMONE

 Produced from arachidonic acid,

 Released from phospholipids by action of
phospholipase A2, phospholipase C
 Produced in almost every organ
 In one pathway arachidonic acid is converted
to prostanoids by a group of enzymes, the
cyclooxygenase system
 A second pathway to produce leukotrienes
by the enzyme 5 lipoxygenase
EICOSANOIDS HORMONE
Prostaglandins

 SAIDS inhibit action of phospholipase

 NSAIDs, such as aspirin and derivatives of
ibuprofen, inhibit cyclooxygenase activity of
PGH2 Synthase
 They inhibit formation of prostaglandins
involved in fever, pain, & inflammation
 They inhibit blood clotting by blocking
thromboxane formation in blood platelets
Long Distance Communication:
Hormones

 Signal Chemicals
 Made in
endocrine cells
 Transported via
blood
 Receptors on
target cells
Long distance cell-to-cell communication

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 Paracrines and Autocrines

 Local
communication
 Signal chemicals
diffuse to target
 Example: Cytokines
– Autocrine–receptor
on same cell
– Paracrine–
neighboring cells Direct and local cell-to-cell communication

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Hormone Receptors
 Receptors : a protein that binds a hormone
with high affinity
 All receptors are proteins
 Have at least two functional domains :
1. A recognition domain binds the hormone
ligand
2. A second region generates a signal that
couples hormone recognition to some
intracellular function
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 Receptor locations
 Cytosolic or Nuclear
– Lipophilic ligand
enters cell
– Often activates gene
– Slower response
 Cell membrane
– Lipophobic ligand
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– Outer surface
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Receptors Intracelluler
 Hormones can diffuse through the lipid bilayer
of the plasma membrane
 receptors intracelluler
 The lipid soluble hormone diffuses into the
cell
 Binds to the receptor  conformational
change
 Binds to specific DNA sequences
response elements (HRE)
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Receptors Intracelluler

 These DNA sequences are in the regulatory

regions of genes.
 Stimulating the transcription of messenger
RNA.
 The messenger RNA travels to the
cytoplasm
 translated into protein

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 Mechanism of
lipid soluble
hormone action

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Action of Steroid Hormones

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Receptors on The Plasma Membrane
 Receptors for the water soluble hormones
 Couple to various second messenger systems
mediate the action of the hormone in the
target cell
 Second messenger :
cAMP
cGMP
 Ca 2+
Phosphoinositide/Diacylglycerol(DAG)
Protein Kinase
Membrane-bound Hormone Receptors
 Second Messenger Systems
1.Cyclic AMP (cAMP)
Polypeptide or glycoprotein hormones
bind to receptor protein
dissociation of a subunit of G-protein
The G-protein is trimer (,  and 
subunit)
The  subunit:
- bound to GDP in the native G protein

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 Second Messenger Systems

1.Cyclic AMP (cAMP)

- the hormone receptor complex
exchange of GTP
- dissociates from G
- stimulates the adenylate cyclase
- ATP is converted to cAMP
ATP cAMP + PPi

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 Second Messenger Systems
2. Cyclic GMP (cGMP)

Membrane bound Guanylate cyclase

is an integral part of the receptor
and hence is structurally similar to
tyrosine specific protein kinases

GTP Guanylate cyclase cGMP

Protein kinase G

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 Second Messenger Systems
3. Calcium
Many cells respond to extracellular
stimuli by altering their intracellular
calcium concentration interaction with
calmodulin
Calcium levels controlled by
phosphoinositide system
Calcium ion may be more of a third
messenger
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 Second Messenger Systems

4. Phosphoinositide/Diacylglycerol (DAG)
Cytosolic calcium ion levels increased by
release from intracellular calcium stores
Controlled by the phosphoinositide
system
Hormonal stimulus  splits phospholipid
PIP2 into IP3 and DAG by phospholipase C

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Phosphoinositide system - Ca2+

 IP3 diffuses through cytoplasm to ER.

 Binding of IP3 to receptor protein in ER
causes Ca2+ channels to open.
 Ca2+ diffuses into the cytoplasm.
– Ca2+ binds to calmodulin.
 Calmodulin activates specific protein
kinase enzymes

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 Phosphoinositide system - Ca2+

 DAG activates protein kinase C

 Alters the metabolism of the cell,
producing the hormone’s effects
 The conversion of inositol phosphate to
inositol is inhibited by lithium ion
treatment of manic-deppressive

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