Hormone

Hormonal Actions
Definition
• Specialized organic molecules that are
synthesized and secreted by ductless glands or
by cells , tissue under specific stimuli and then
transmitted via the bloodstream to act on
distant target cells
 Hormones

• Long-range messengers
• Secreted into blood by endocrine glands in response to
appropriate signal
• Exert effect on target cells some distance away from
release site
– Neurohormones
• Hormones released into blood by neurosecretory
neurons
• Distributed through blood to distant target cells
Endocrine Signaling
Classification

of Hormones
 Chemical Classification of Hormones
• Aminoacids (Amines):
– Hormones derived from tyrosine and tryptophan.
– Dopamine ,Nor Epinephrine, Epinephrine, Thyroxine,5-HT.
• Polypeptides and proteins:
– Polypeptides:
• Chains of < 10 amino acids in length. eq Anti diuretic Hormone.
– Protein hormones:
• Polypeptide chains with > 10 amino acids. eq Growth hormone.
• Lipids derived from cholesterol.
– Are lipophilic hormones.
• Testosterone , Estradiol , Cortisol, Progesterone.
 Protein Hormone Synthesis
• Synthesized in rough endoplasmic reticulum(RER)
• Single gene determine single protein and peptide
hormone
Stages : Preprohormone:
– Prohormone is large polypeptide chain molecule in(RER)
with signal peptide .
• Prohormone:
– Precursor is a longer chained polypeptide that is cut from
signal peptide.
• Prehormone: shows folding , and intra molecular linkages
– Molecules in Golgi apparatus that are inactive until
changed into hormones by target cells.
• T4 converted to T3.
Mechanism of Hormone action
 Receptor function effects of [hormone] on tissue

• Normal tissue responses are produced only when

[hormone] are present within physiological range.
• Priming effect (upregulation):
Increase number of receptors formed on target cells in
response to particular hormone.
Desensitization (downregulation):
Prolonged exposure to high [polypeptide hormone].
• Decrease in number of receptors on target
cells.Insulin in adipose cells.
• Pulsatile secretion may prevent downregulation
 Hormones That Bind to
Cytoplasmic Receptor Proteins
Hormones binds to cell membrane receptor
protein
• Binding of extracellular messenger (first
messenger) to matching receptor brings about
desired intracellular response by either
a. Opening or closing channels linked to receptor
b. By activating enzymes linked to receptor
c. Activating second-messenger systems via linked
protein(G-PROTEIN)
• Protein (ENZYMES) activated
• Relays message to intracellular proteins (KINASES) that
carry out dictated response
RECEPTOR LINKED TO CHANNELS
 Opening of receptor-channel
when an extracellular messenger
binds
RECEPTOR LINKED TO ENZYMES

AND KINASES
Rule of four 4
Adenylate Cyclase-cAMP ()
Membrane phospholipid -Phospholipase
system
 Guanylyl cyclase-cyclic GMP system

• Example – ANP , Nitric oxide and enterotoxin of E coli.

 G protein diseases
• Increase G protein responses
1. Acromegaly
2. McCunne -Albright Syndrome

Decrease G protein responses

1. Type 1 psuedohypoparathyroidism
Tyrosine Kinase
GROWTH FACTORS
RTK-RAS-MAPK PATHWAY
ANTI –CANCER DRUGS
PIGGLET
JAK -STAT PATHWAY
IMMUNOSUPPRESSENT DRUGS
Hormones That Bind to Nuclear
Receptor Proteins
 Nuclear Hormone Receptors

• Steroid receptors are located in cytoplasm and in the

nucleus.
• Each nuclear hormone receptor has 3 regions:
– C-terminus ,A ligand (hormone)-binding domain.
– DNA-binding domain. Binds to specific region of DNA
called HRE (hormone regulatory element).
– N-terminus domain, has trans activating functions
• Receptor must be activated before binding to hormone.
eq . In adrenal hormone binds to C-terminus by removing
HEAT SHOCK PROTEIN.
Hormones That Bind to Nuclear Receptor
Proteins
 Nuclear Hormone Receptors
• ACTIVATED RECEPTOR undergo translocation
& dimerization ( HRE binds to 2 HR dimeric
complexes)
• Hormone binding to receptor
(activated)remove the suppressor effect of
unligand one.
• Activated receptor interact with AP-1(c-Jun
and c -Fos bound to genes.
 Tyrosine Kinase
• Hormones binds to ligand–binding site on plasma
membrane, activating enzymatic site in the
cytoplasm.
• receptor consists of 2 units that dimerize when
they bind with insulin.( Process of 2 receptor
units coming together at the 2 half-sites.)
• Autophosphorylation occurs, increasing tyrosine
kinase activity.
• Phosphorylates various enzymes (Jak and Stat
pathway)
•
Steroid hormone
synthesis
• Synthesize from
cholesterol.
• Each type
requires a
sequential series
of enzymatic
reaction
• Alteration of
biological activity
can occur outside
 Adenylate Cyclase-cAMP
• HR complex formation
• Activation of G-protein
• Activation of adenyl cyclase if α (s) is stimulate.
• Adenyl cyclase catalyses the conversion of ATP to CAMP.
• CAMP activates protein kinase A
• Subunits of protein kinase A phosphorylates the serine
and threonine residue and forms phosphoproteins.
• Phosphoproteins induces cell function.
• Eq. GHRH , CRH , GnRH , FSH and LH
 Effector system
Via G-proteins
1. Adenylyl cyclase-cAMP system.
2. Membrane phospholipid -Phospholipase
system.
3. Guanylyl cyclase-cyclic GMP system
Others
4. Calcium calmodulin system.
5. Tyrosine kinase system
Coupling molecule
G proteins
• Trimers linking
proteins that
Links Receptors
to Effector
molecule.
• Effector
molecule
generate second
messengers that
mediate the
intercellular actions
 Membrane phospholipid -Phospholipase
system
• HR complex formation
• Activation of G-protein
• Activation of phospholipase C if α (s) is stimulated.
• Phospholipase C splits phospholipid into IP3 and DAG.
Both derivatives serve as 2nd messengers.
• IP3 diffuses through cytoplasm to ER.
– Binding of IP3 to receptor protein in ER causes Ca2+
channels to open.
• DAG stimulate intracellular enzyme phosphokinase- C.
• Eq.Epinephrine,ADH,TRH and Angiotensin-II
Activation of
second
messenger
pathway via G-
Protein couples
receptors
– By activating
receptor
enzymes