THE ENDOCRINE

SYSTEM

HORMONES
CLASSIFICATION
OF HORMONES
LECTURE 01
INTRODUCTION &
DEFINITION
• The word hormone in Greek
means ‘to arouse to
activity’.
•HORMONES,
NEUROTRANSMITTERS
AND THE IMMUNE SYSTEM
are the links between the
extracellular events and the
changes occurring within the
cells.
•Entire field of
Endocrinology is devoted
to the study of hormones.
A hormone can be defined as a substance
produced by an endocrine gland, secreted into
the blood and delivered to a target organ on
which it will act and elicit an appropriate
physiological response.
Hormones can also be classified according to their
ways of communication—autocrine, paracrine
and endocrine.
The hormones have an intimate association with the
hypothalamus and pituitary gland in the brain.
 Signal transduction is the study of how a cell communicates.
 Every cell is able to communicate through having evolved the ability
to produce, recognize, interpret and respond to signals in its
environment.
 The word ‘signals’ in this context refers to nothing more than
chemical molecules that are floating around. The first messengers,
which are generally the protein hormones, initiate signal
transduction at the plasma membrane after binding to the
receptor, through the secondary messengers.
 • The secondary messengers include cAMP cGMP, calcium,
phosphoinositide and calmodulin.
ENDOCRINE
SIGNALING

 Specialized sender cells in glandular tissues

synthesize, package and secrete molecules
called hormones.
 Hormones are molecules secreted into the blood
for long distance transport to the target cells in
various tissues.
 Most of the body cells are exposed to the
hormones but only those cells that express specific
receptors for that hormone are the target cells
 PARACRINE SIGNALING

 This kind of signaling is greatly restricted by the distance

over which the molecules can travel by passive
diffusion.
 This limits the responses only to the target cells in the
immediate vicinity of the sender cell.
 Because the secreted local mediators are not massively
diluted , their concentration near target cell can be
fairly high.
 Thus, Paracrine signaling can be used for rapid and
localized communication between cells
INTRACRINE
SIGNALING

 Intracrine signaling is specific to mediators

that signal through cytosolic or nuclear
receptors, as they can confer signaling effects
without first being secreted from the cell of
origin.
 e.g., Peptides of the renin–angiotensin
system: angiotensin II and angiotensin (1-
7) Fibroblast growth factor 2.
• In JUXTACRINE signaling, cells communicate through
1. Gap junction channels, that allow direct transfer of
small ions or metabolites between neighboring cells
2. By the interaction of a protein expressed on the
surface of sender cell, with a receptor protein on the
surface of the target cell
 This interaction changes the conformation of the
receptor protein and triggers a cascade of intra
cellular events
• Important element of juxtacrine signaling are a
variety of proteins involved in cell- cell adhesion
 AUTOCRINE
SIGNALING

Autocrine signaling occurs when one cell is both

the sender and the target cell
 Often used by embryonic and neonatal organisms
during tissue and organ development and by adult
organism as part of immune and inflammatory
responses.
 Sender cell provides both the secreted molecules
and a receptor for that molecule.
 SYNAPTIC
OR
NEURONA
L
SIGNALIN
Neurons secrete signaling molecules called
neurotransmitters, which travel over short
Gdistances to reach the target cells.
 Receptors on the target cells have relatively low
affinity for the neurotransmitters.
 Neurotransmitters dissociate from their receptors
following a decrease in the local concentration,
leading to rapid termination of neurotransmission.
 ECTOPIC PRODUCTION OF
HORMONES
 ACTH: Oat cell carcinoma lungs, thymic carcinoid
and bronchial CA, CA thyroid, pancreatic CA.
 Vasopressin: CA bronchus.
 HCG: testicular tumors, choriocarcinoma

HORMONE
 Defects in receptors
RESISTANCE
 Defects in post receptor mechanism
 Development of antibodies to hormone
 Development of antibodies to hormone
receptors
 Absence of target cells
 CLASSIFICATION OF
HORMONES
HORMONES CAN BE DIVIDED INTO TWO GROUPS
ON THE BASIS OF MODE OF ACTION.
GROUP 1. HORMONES THAT BIND TO
INTRACELLULAR RECEPTORS.
GROUP II. HORMONES THAT BIND TO CELL
SURFACE RECEPTORS.
Releasing and release inhibiting hormones
produced by the hypothalamus:
These hormones affect the activity of the anterior pituitary where they
reach via the hypothalamic-hypophyseal portal blood vessels.
Their list is given below:
a. Thyrotropin releasing hormone (TRH): It is a tri-peptide.
b. Cortico-tropin releasing hormone (CRH): It has 41 amino acids residues.
c. Growth hormone releasing hormone (GHRH): It has 44 amino acids residues.
d. FSH releasing hormone (FSHRH): It has 10 amino acids residues.
e. LH releasing hormone (LHRH): The FSHRH and LHRH or gonadotropin releasing
hormone (GnRH) is used for them.
f. Prolactin releasing hormone (PRH): It appears to be a peptide.
g. Growth hormone releasing inhibiting hormone (GHRIH): It is also called
somatostatin; it has 14 A.A. residues.
The hypothalamus also produce prolactin release inhibiting hormone (PRIH)
which is dopamine. Dopamine is not a peptide but is one of the
catecholamines.
h. Ovary: Relaxin, inhibins, activins.
x. Testis: Inhibins, Activins.
xi. Miscellaneous: These include erythropoietin, angiotensin-II and angiotensin-
III, kinins, atrial natriuretic peptide and two other hormones closely related to
CLASSIFICATION OF HORMONES
BASED UPON CHEMICAL
STRUCTURE
1. PEPTIDES:
Amino acids number varies.
Residues and their length : ranges few to many
Following are the glands along with their
peptide hormones.
ANTERIOR PITUITARY:
 Growth hormone (GH) [somatotropin.
 ACTH, {corticotropin} and prolactin are pure
peptides while
 TSH {thyrotropin}
 (FSH) and (LH) are glycoproteins
 ii. POSTERIOR PITUITARY: Vasopressin
(antidiuretic hormone, ADH) and oxytocin.
iii. PARS INTERMEDIATE OF THE PITUITARY: Alpha
MSH and gamma MSH (collectively called
melanotropin or intermedin); in addition gamma
lipotropin, corticotropin like intermediate lobe
peptide (CLIP) and other fragments of pro-
opiomelanocortin (POMC).
iv. PANCREAS: Insulin, glucagon, somatostatin
and pancreatic polypeptide.
 V. PARATHYROID GLANDS: Parathyroid hormone
(PTH) also called parathormone.
 Vi. THYROID: Calcitonin
 Vii. GIT: Gastrin, secretion and cholecystokinin-
pancreozymin now called cholecytokinin (CCK-
PZ or only CCK) are the established hormones of
the GIT while many other hormones of GIT are
 2. STEROIDS:
These have the steroid rings in their
molecules and are derived from
cholesterol. These are secreted by
the following glands:
i. Adrenal Cortex: Aldosterone,
cortisol and androgenic ( producing
male characteristics) hormones
especially dehydro-epiandrosterone
(DHEA) and andro-stenedione.
ii. Ovary : Estrogens and Progesterone
iii. Testis: Testosterone.
iv. Skin: Vitamin D3
( CHOLECALCIFEROL) originates from a
steroid namely 7-dehydrocholesterol
present in the skin when the latter is
exposed to ultraviolet rays. As this
vitamin is produced in the body, it may
be considered as a hormone.
3. AMINES: This group has amino group in their
structure and includes the following:
i. Acetylcholine: It acts as a neurotransmitter.
ii. Catecholamines: Nor-adrenaline, adrenaline
and dopamine.
iii. Melatonin: It is produced in the pineal body.
AMINO ACID DERIVATIVES: Tetra-idothyronine
(T4)also called thyroxine and triiodothyronine
(T3) are iodinated A.A.
LIPID DERIVATIVES: These are eicosanoids derived
from 20 carbon containing polyunsaturated fatty
acids and comprise prostanoids, lipoxins and
leukotrienes.
 Protein hormones: e.g Insulin, Glucagon.
 - Steroid hormones: e.g. Sex hormones, Mineralo-
corticoids.
 - Amino acid-derived hormones: eg.,Epinephrine,
CLASSIFICATION OF HORMONES ACCORDING TO
LOCATION OF RECEPTORS AND THE NATURE OF
THE SIGNAL

GROUP I. Hormones that bind to intracellular

receptors
GROUP II. Hormones that bind to cell surface
receptors
[Link] coupled to effectors by second
messengers
A. The second messenger is c-AMP.
B. The second messenger is c-GMP.
C. The second messenger is calcium or
phosphatidyl-inositol or both.
2. Receptors coupled directly to effector
molecules
 RECEPTORS ACCORDING TO LOCATION

Intra Cellular Receptors Cell Surface Receptors

Steroid T3, T4, Vit D & Other Lipophilic Compounds

Ligand Gated
Ion Channel Catalytic
Receptors Receptors Coupled To
Adenylyl And Guanylyl Cyclase

Receptors Coupled
To
Phosphatidyl
Inositol Hydrolysis
 Classification of Hormones
according to location of
receptors and the nature of the
signal
[Link] that bind to intracellular
receptors
 Androgens
 Calcitriol (1,25[OH]2-D3 )
 Estrogens
 Glucocorticoids
 Mineralocorticoids
 Progestins
 Retinoic acid
 Thyroid hormones (T3 and T4 )
II. Hormones that bind to cell surface receptors
Receptors coupled to effectors by second messengers
A. The second messenger is c AMP
 Catecholamines
 Adrenocorticotropic hormone (ACTH)
 Antidiuretic hormone (ADH)
 Human chorionic gonadotropin (hCG)
 Corticotropin-releasing hormone
 Follicle-stimulating hormone (FSH)
 Glucagon
 Luteinizing hormone (LH)
 Melanocyte-stimulating hormone (MSH)
 Parathyroid hormone (PTH)
 Thyroid-stimulating hormone (TSH)
B. The second messenger is c GMP
 Atriopeptins e.g., atrial natriuretic factor
 Chemokines e.g., nitric oxide (NO)
C. The second messenger is calcium or
phosphatidylinositols (or both)
 Acetylcholine
 α1-Adrenergic catecholamine.
 Angiotensin-II
 Antidiuretic hormone (vasopressin)
 Gonadotropin-releasing hormone
(GRH)
 Oxytocin
 Platelet-derived growth factor (PDGF)
 Thyrotropin-releasing hormone (TRH)
2. RECEPTORS COUPLED
DIRECTLY TO EFFECTOR
MOLECULES
A. LIGAND GATED ION CHANNELS
A. Nicotinic acetylcholine
receptor
B. GABA receptors
B. ENZYME LINKED OR CATALYTIC
(A KINASE OR
PHOSPHATASE
CASCADE) RECEPTORS
• Epidermal growth factor
• Erythropoietin
• Growth hormone (GH)
• Insulin
• Insulin-like growth factors I
and II
• Platelet-derived growth
THE LOCATIONS FOR THE
DIFFERENT
TYPES OF HORMONE RECEPTORS
These are generally the following:
 In or on the surface of the cell
membrane. The membrane receptors
are specific mostly for the protein,
peptide, and catecholamine
hormones.
 In the cell cytoplasm. The primary
receptors for the different steroid
hormones are found mainly in the
cytoplasm.
 In the cell nucleus. The receptors for
the thyroid hormones are found in the
nucleus and are believed to be located in
direct association with one or more of the
chromosomes.
 FORMATION OF HORMONE RECEPTOR
COMPLEX
 The first step of a hormone's action is to bind to
specific receptors at the target cell.
 Cells that lack receptors for the hormones do not
respond.
 When the hormone combines with its receptor,
this usually initiates a cascade of reactions in
the cell, with each stage becoming more
powerfully activated so that even small
concentrations of the hormone can have a large
effect.
CHARACTERISTICS OF RECEPTOR PROTEINS
 Hormonal receptors are large proteins, and
each cell that is to be stimulated usually has
some 2000 to 100,000 receptors.
 Each receptor is usually highly specific for a
single hormone. This determines the type of
hormone that will act on a particular tissue.
 The target tissues that are affected by a
hormone are those that contain its specific
receptors.
THE LIGAND–RECEPTOR COMPLEX IS THE
SIGNAL FOR GROUP I HORMONES
 The lipophilic group I hormones diffuse
through the plasma membrane of all cells
but only encounter their specific, high-
affinity intracellular receptors in target
cells
 These receptors can be located in the
cytoplasm or in the nucleus of target
cells
 The hormone–receptor complex first
undergoes an activation reaction
 Receptor activation occurs
by at least two mechanisms

• Glucocorticoids diffuse
across the plasma
membrane and encounter
their cognate receptor in
the cytoplasm of target
cells
• Ligand–receptor binding
results in a conformational
change in the receptor
leading to the dissociation
of heat shock protein
90 (hsp90)
 This step appears to be
necessary for
subsequent nuclear
localization of the
gluco-corticoid
receptor.
 This receptor also
contains a nuclear
localization sequence
that is now free to
assist in the
translocation from
cytoplasm to nucleus.
 The activated receptor moves into the
nucleus and binds with high affinity to a
specific DNA sequence called the hormone
response element (HRE).
 The DNA-bound, liganded receptor serves as
a high-affinity binding site for one or more
coactivator proteins, and accelerated gene
transcription typically ensues when this
occurs
 By contrast, certain hormones such as
the thyroid hormones and retinoids
diffuse from the extracellular fluid
across the plasma membrane and go
directly into the nucleus.

 In this case, the cognate receptor is

already bound to the HRE (the thyroid
hormone response element [TRE])
 However, this DNA-bound receptor
fails to activate transcription because
it exists in complex with a co-
repressor.
 Indeed,this receptor-corepressor
complex serves as an active repressor
of gene transcription
 Theassociation of ligand with the
receptor results in dissociation of the
corepressor(s).

 The liganded receptor is now capable

of binding one or more coactivators
with high affinity, resulting in the
 GROUP II (PEPTIDE & CATECHOLAMINE) HORMONES HAVE
MEMBRANE RECEPTORS & USE INTRACELLULAR MESSENGERS
 Many hormones are water-soluble, have no transport proteins
(and therefore have a short plasma half-life), and initiate a
response by binding to a receptor located in the plasma
membrane
 The mechanism of action of this group of hormones can best
be discussed in terms of the intracellular signals they
generate.
These signals include
c AMP, a nucleotide derived from ATP through the
action of adenylyl cyclase
c GMP, a nucleotide formed by guanyl cyclase
 Ca2+
 Phosphatidyl-inositol.
 Such molecules are termed second messengers as their
synthesis is triggered by the presence of the primary
hormone binding its receptor
 GENERAL CHARACTERISTICS OF
HORMONES
• Most hormones are either derived from lipids or
proteins or modified from amino acids such as tyrosine.
• Hormones that are lipophilic, with the exception of
thyroid hormones, are derived from cholesterol and are
referred to as steroid hormones.
• Hormones that are water-soluble, bind to the plasma
membrane of the cell. They function via secondary
messengers. These are protein hormones.
Hormone-producing cells are usually not randomly
distributed.
•Hormones related to glucose metabolism are all situated
near one another. For example insulin, glucagon,
pancreatic polypeptide and somatostatin are all related
to glucose metabolism and are present in the pancreas.
• Some hormones may be modified before they
attain full biological activity, e.g. Insulin is
secreted as pre-pro-insulin and then pro-insulin.
• Hormones can also be secreted in the final
active form, e.g. Aldosterone.
• Hormones that are secreted from different cells and have
different cell specificity can have structural similarities, e.g.
Thyroid-stimulating hormones (TSH),
luteinizing hormone (LH),
Follicle-stimulatin hormone (FSH) and
human chorionic gonadotropin (hCG).
•All
these hormones are made up of α- and β-subunits. The
αβ-subunits are all identical. The β-subunit is the one that
confers biological activity on the molecule.
•Very low concentrations of hormones are present in blood.
They are present in such small quantities as nanomoles and
picomoles.
• Turnover of the hormones is varied and rapid. Half-life of
the protein hormones is of seconds or minutes, whereas the
steroid hormones have a half-life of days.
• All hormones, whether protein or steroid, associate with
receptors in the cytoplasm or nucleus and then mediate
response with or without the help of secondary messengers.
Different tissues respond differently to a hormone e.g. Gluco-
corticosteroids stimulate the breakdown of proteins in
muscle while they stimulate the synthesis of proteins in liver.
• Steroid hormones being lipophilic require binding proteins
to carry them in the blood. Only free hormones are found to
be biologically active.
• Measurement of hormones is carried out by using methods
such as radioimmunoassay, bioassays and radio-receptor