HORMONE:
MECHANISM & ACTION
HORMONE
➢A hormone is chemical regulatory
substance, secreted by endocrine glands.
➢It passes through blood stream to reach the
tissues on which it acts. These tissues are
called “target tissues”.
TARGET TISSUE
Target tissue of a certain hormone is the
tissue, which contains the specific receptors
of that hormone
GENERAL PRINCIPLES OF HORMONE
ACTION
• Trophic hormone:- A hormone that has its primary function the
regulation of hormone secretion by another endocrine gland
• Synergism-when different hormones work together and have a
greater effect than individual hormone action
• Permissiveness-a small amount of one hormone allows a second
hormone to have its full effect on a target cell; i.e. first hormone
‘permits’ the full action of the second hormone
• Antagonism-one hormone produces the opposite effect of the
other
• The processes involve in both negative and positive feedback.
For example, if A>B>C>D, increase in D causes inhibition of A i.e.
negative feedback. If D decreases, A production is triggered, i.e.
positive feedback.
MECHANISM OF HORMONE ACTION
The hormones fall into two general classes based on
their solubility in water.
1. Hydrophilic Hormone: The water soluble hormone.
They are transported simply dissolved in blood
Examples: the catecholamines (epinephrine
and norepinephrine) and peptide/protein
hormones.
2. Lipophilic Hormone: They are poorly soluble in
water. So they cannot be dissolved in watery blood.
They bind to plasma protein and present in the
blood in protein bound form. They are lipid soluble.
Examples: The lipid soluble hormones include
thyroid hormone, steroid hormones and Vitamin
D3
Broad Classification (Structure)
Hydrophillic Lipophillic
Steroid and thyroid hormones
Proteins, peptide hormones
& catecholamines
Activate genes on binding with
Primarily act through second receptors in the nucleus
messenger system
Largely bound to plasma proteins
Circulate mainly dissolved in
the plasma
HORMONE RECEPTORS
• Definition:
Cell-associated recognition molecules which
are protein in nature.
• Functional sites:
Two functional sites:
➢Recognition site: It binds the hormone
specifically.
➢Signaling site: It couples hormone binding to
intracellular effect
HORMONE RECEPTORS
Location : Receptors may be:
➢Intracellular receptors: (in the cytosol or
in the nucleus)
➢Cell-membrane receptors: (in the plasma
membrane).
I- CLASSIFICATION ACCORDING
TO CHEMICAL NATURE
AMINO ACIDS
PROTEINS DERIVED STEROIDS
I- CLASSIFICATION ACCORDING
TO CHEMICAL NATURE
A- PROTEIN HORMONES:
➢ Large polypeptides: e.g. insulin and
parathyroid hormone
➢ Small polypeptides: e.g. ADH (9a.a.),
oxytocin (9a.a.)
➢Glycoprotein hormone: e.g. FSH, LH, TSH,
HCG
I- CLASSIFICATION ACCORDING TO
CHEMICAL NATURE
B- AMINO ACID DERIVED HORMONES:
➢Thyroid hormones and catecholamines
are derived from tyrosine.
➢Melatonin is derived from tryptophan
I- CLASSIFICATION ACCORDING TO
CHEMICAL NATURE
C- Steroid hormones:
• These hormones are derived from cholesterol.
e.g.
➢ Glucocorticoids.
➢ Mineralocorticoids.
➢ Sex hormones (Testosterone, progesterone,
oestrogen etc.)
II-CLASSIFICATION ACCORDING TO
MECHANISM OF ACTION
A- Hormones, which bind to intracellular
receptors.
B- Hormones, which bind to membrane receptors
Hormones bind to Hormones bind to cell
intracellular RCs membrane RCs
▪ LIPOPHYLIC (are poorly soluble ▪ HYDROPHILIC (The water
in water) soluble hormone)
▪ NEED TRANSPORT PROTEINS ▪DO NOT NEED TRANSPORT
TO REACH TARGET TISSUES PROTEIN
▪ LONG PLASMA HALF-LIFE ▪ SHORT PLASMA HALF-LIFE
(HOURS TO DAYS). ▪ (MINUTES).
▪ ACTION IS MEDIATED BY ▪ ACTION IS MEDIATED BY
FORMING HORMONE- ▪ SECOND MESSENGER.
RECEPTOR COMPLEX
▪ INCLUDE: STEROID , THYROID , INCLUDE: the catecholamines
▪ CALCITRIOL and Vitamin D (epinephrine and norepinephrine)
and peptide/protein hormones
THE SECOND MESSENGER
➢ Is the signal produced as a result of hormone binding
to its cell membrane receptor.
➢ It mediates the effects of the hormone.
➢ The second messenger may be:
Cyclic Adenosine Monophosphate (cAMP).
Cyclic Guanosine Monophosphate (cGMP).
Calcium or phosphatidyl inositol or both.
Protein kinase cascade.
• N.B. The hormone is considered to be the first messenger
Signal Amplification Via 2nd Messenger Pathways
Initial signal is in the form of hormone
which acts as ligand whose concentration
is just one/per receptor. The hormonal
response has got multiple steps, and each
step multiplies the signal (cascading
effect) that finally leading to million fold
amplification, i.e. one hormone molecule
mediating its effect through million of
molecules. This process is known as
signal amplification.
TYPES OF RECEPTORS &
LOCATION
NUCLEAR
INTERNAL
CYTOPLASMIC
RECEPTOR
CELL
EXTERNAL
MEMBRANE
HOW LIPID-SOLUBLE HORMONES WORK?
• Binding to specific cell receptor in the cell
membrane and form hormone-cell receptor
complex, which diffuses to nucleus
• The receptor is eventually released for re-use
• Steroid activates a specific gene to produce
mRNA
• mRNA pass out into the cytoplasm and initiates
protein [enzyme] synthesis
❖why do they penetrate the cell?
✓ the whole process is called mobile-receptor
hypothesis in which a steroid hormone is not attached
to the plasma membrane, but seem to move freely in
the nucleoplasm
HOW LIPID-SOLUBLE HORMONES WORK?
• Step-1: Free lipophilic hormone (hormone not bound with
its plasma protein carrier) diffuses
through the plasma membrane of the target cell and
binds with the receptor which is intracellularly located
inside the cytosol/or in the nucleus.
• Step-2. Each receptor has specific binding region with
hormone and another region with binding with DNA.
Receptor alone cannot bind to DNA unless it binds to
hormone. Once the hormone is bound to receptor, the
hormone receptor complex binds to specific region of
DNA known as Hormone response element(HRE).
• Step-3: Transcription of gene
• Step-4: m RNA transported out of nucleus into the
cytoplasm
• Step-5: Translation at Ribosome
• Step-6: Protein/enzyme released from ribosome
• Step-7: protein/enzyme mediate ultimate response
STEROID HORMONES: MOLECULAR ACTION
HOW LIPID-SOLUBLE HORMONES
WORK?
WATER-SOLUBLE HORMONES
HOW WATER-SOLUBLE HORMONES
WORK?
HOW WATER-SOLUBLE
HORMONES WORK?
• ●1 A water-soluble hormone (the first messenger) diffuses from
the blood through interstitial fluid and then binds to its receptor
at the exterior surface of a target cell’s plasma membrane. The
hormone– receptor complex activates a membrane protein
called a G protein. The activated G protein in turn activates
adenylate cyclase.
• ●2 Adenylate cyclase converts ATP into cyclic AMP (cAMP).
Because the enzyme’s active site is on the inner surface of
the plasma membrane, this reaction occurs in the cytosol
of the cell.
• ●3 Cyclic AMP (the second messenger) activates one or more
protein kinases, which may be free in the cytosol or bound to
the plasma membrane. A protein kinase is an enzyme that
phosphorylates (adds a phosphate group to) other cellular
proteins (such as enzymes). The donor of the phosphate
group is ATP, which is converted to ADP.
HOW WATER-SOLUBLE
HORMONES WORK?
• ●4 Activated protein kinases phosphorylate one or more cellular
proteins. Phosphorylation activates some of these proteins and
inactivates others, rather like turning a switch on or off.
• ●5 Phosphorylated proteins in turn cause reactions that produce
physiological responses. Different protein kinases exist within different
target cells and within different organelles of the same target cell. Thus,
one protein kinase might trigger glycogen synthesis, a second might
cause the breakdown of triglyceride, a third may promote protein
synthesis, and so forth. As noted in step
• ●6. phosphorylation by a protein kinase can also inhibit certain proteins.
For example, some of the kinases unleashed when epinephrine binds to
liver cells inactivate an enzyme needed for glycogen synthesis
.
• ●7 After a brief period, an enzyme called phosphodiesterase inactivates
cAMP. Thus, the cell’s response is turned off unless new hormone
molecules continue to bind to their receptors in the plasma membrane
REGULATION OF HORMONE
SECRETION
FEEDBACK
CONTROL
involve the secretion of
catecholamines by POSITIVE NEGATIVE
adrenal medulla. FEEDBACK FEEDBACK
REGULATION OF HORMONE SECRETION
Feedback Control HPT Axis
NEGATIVE FEEDBACK Hypothalamus
TRH +
-
Anterior
Pituitary
Long loop feedback involves
+ TSH
the hormone feedback all the
Thyroid
way back to the hypothalamic- -
+
pituitary axis
T3 , T4
Short loop feedback involves the Increased
metabolism
anterior pituitary hormone
feedback on the hypothalamus
to inhibit the hypothalamic T3 and T4
releasing hormones inhibits secretion
HormoneMetabol
ism
of TRH and TSH
REGULATION OF HORMONE SECRETION
Female HPG Axis
Feedback Control
POSITIVE FEEDBACK Hypothalamus
+ GnRH
involve the effect of estrogen Anterior
Pituitary
on secretion of FSH and LH by
+
anterior pituitary as well as the - +
LH FSH
effect of oxytocin. - +
+
Ovaries
The increase in contractions causes more +
oxytocin to be released and the cycle goes
Estrogen Progesterone
on until the baby is born. The birth ends
the release of oxytocin and ends the
positive feedback mechanism.
HormoneMetabolism
Hypothalamic Pituitary Gonada Axis HPG Axis
CLEARANCE OF HORMONES
Hormones are cleared by:
1.Metabolic destruction by tissues/ target cells.
2.Binding with the tissues
3.Excretion by liver into bile.
4.Excretion by kidneys into urine.
Water soluble hormones(peptides and
catecholamines) are degraded by enzymes in the
blood or tissues and are excreted by kidneys or liver.
They have a short half life.
Lipid soluble hormones(steroids) are protein
bound and are cleared slowly.
