Hormones:

Medical Biochemist
Ministry of health and population.
 INTRODUCTION

Communication system to coordinate its biological

function in our body consists of :

– Nervous system: coordinates the body function through

the transmission of electrochemical impulses

– Endocrine system: acts through a wide range of chemical

messenger called hormones
 HORMONES: DEFINITION
 Organic substances
 Produced in small amounts by specific tissues
(endocrine glands)
 Secreted into the blood stream
 Control the metabolic and biological activities in
the target cells

 regarded as the chemical messengers involved in

the transmission of information from one tissue
to another and from cell to cell
Function of hormones:

 HOMEOSTASIS / Maintenance of internal

environment (PTH, aldosterone, calcitriol,
calcitonin)
 Reproduction
 Growth and development
 Production, utilization and storage of energy
(Insulin, glucagon, cortisol)
Transport of Hormones

After entering the blood hormones either remain in free from or

bind with a specific carrier protein.
A. Water Soluble Hormones
 Peptide hormones & biogenic amines readily dissolve in the plasma.
 So, they do not require special mechanism for their transport.

B. Transport of Steroid Hormones

 Thyroxine, steroid hormones & vitamin D are relatively insoluble in
plasma & circulate in the bound form.
 In blood, more than 90% of thyroid & steroid hormones are bound to
plasma proteins.
 The transport proteins are specific for hormones.
 However, few nonspecific proteins are also involved in the process of
hormone transport.
Classification of Hormones
A. Based on the chemical structure

B. Based on the mechanism of action

C. Based on the anatomical position

A) Classification based on the chemical
nature
 1) Protein or peptide hormones
• Hormones of the hypothalamus and pituitary,
Insulin, glucagon, the parathyroid hormone,
calcitonin,
 2) Steroid hormones
• Adrenocorticosteroid hormones , sex hormones

 3) Amino acid derivatives

• Epinephrine, norepinephrine, T3, T4
 Classification based on Mechanism of Action:
Two broad groups ( Group I & Group II) based on the location of
receptors to which they bind and the signals used to mediate
their action.
Group 1: Hormones that bind to intracellular receptors.

Group 2: Hormones that bind to cell surface receptors.

a) Second messenger is c AMP 
eg. ACTH, ADH, PTH, TSH, glucagon

b) Second messenger is c GMP. eg. ANP, NO

c) Second messenger is calcium or phosphoinositol or both

eg. Ach, α Adrenergic, TRH

d) Second messenger is a kinase or phosphatase cascade.

eg. Growth factors , Insulin
Hormone Receptors:
Hormone receptors are membrane proteins which are specific for
each hormone.

Their sensitivity or responsiveness is determined by:

Number of receptors; larger the number, greater is the

response.
Affinity of receptors; higher the affinity, greater is the response

The sensitivity of receptors can be changed by the change in

number of receptors, which can occur by:

Increase or decrease in synthesis of receptors

Increase or decrease in degradation of receptors.
 Site of Hormone Receptors:

 In the surface of cell membrane, e.g. protein or

peptide hormones and catecholamines.

In the cytoplasm, e.g. steroid hormones.

In the cell nucleus, e.g. Thyroxine.

There are about 2000-100,000 receptors on each cell.

 Group I /Lipophilic Hormones (Hydrophobic Hormones)

Hormones that are not soluble in aqueous medium, but

soluble in lipid i.e lipophilic.

They can easily cross the cell membrane.

Thus, they can enter target cells and bind to intracellular

receptors to carryout their action.

• Examples: Thyroid hormones, Steroid hormones;

 Group I /Lipophilic Hormones (Hydrophobic Hormones)

Hormones that are not soluble in aqueous medium, but

soluble in lipid i.e lipophilic.

They can easily cross the cell membrane.

Thus, they can enter target cells and bind to intracellular

receptors to carryout their action.

• Examples: Thyroid hormones, Steroid hormones;

 Mechanism of action of steroid hormones
– Pass through the cell membrane
– Binds to specific receptors.
– Then enters the nucleus to bind with the HRE of
cellular DNA which then activates certain genes
(Direct gene activation).
– mRNA is synthesized in the nucleus and enters
the cytoplasm and promotes protein synthesis
for:
• Enzymes as catalysts
• Tissue growth and repair
• Regulate enzyme function
Steroid hormone Mechanism (group I)
Steroid hormone Mechanism (group I)
Group II /Hydrophilic Hormones (Lipophobic Hormones)

Hormones that are soluble in aqueous medium

They cannot cross the cell membrane,

Thus, they bind to receptor molecules on the

outer surface of target cells, initiating reactions
within the cell that ultimately modifies the
functions of the cells.

Examples: Insulin, Glucagon, Epinephrine.

Group II hormones Contd:

The endocrine gland releases hormones that bind

with specific receptor on target cells and trigger
intracellular signals by:

Altering membrane permeability

Acting through 2nd messenger system

Activating specific genes to form new proteins

The Receptor For Water Soluble Hormone-Cellular surface
receptors

Classified into three types:

1. Ion- channel linked receptors → Transmitter gated ion

channels Eg.Ach, Na+,Ca+

2. G- Protein linked receptors → The interaction between

the receptor and target protein is mediated by third protein
called G Protein

3. Enzyme linked receptors → When activated, either

function directly as enzyme or associated with enzymes.
The Receptor For Water Soluble Hormone-Cellular surface
receptors

Classified into three types:

1. Ion- channel linked receptors → Transmitter gated ion

channels Eg.Ach, Na+,Ca+

2. G- Protein linked receptors → The interaction between

the receptor and target protein is mediated by third protein
called G Protein

3. Enzyme linked receptors → When activated, either

function directly as enzyme or associated with enzymes.
1. Ion channel linked receptors:

eg. virtually all the neuro-transmitter substances such

as acetylcholine& epinephrine combine with receptors
in the postsynaptic membrane.

This causes a change in the structure of receptor

usually opening or closing a channel for one or more
ions
2. G-protein linked hormone receptors:

Many hormones activate receptors that indirectly

regulate the activity of target proteins (eg.,enzymes or
ion channels) by coupling with a group of cell
membrane proteins called heterotrimeric GTP-binding
proteins (G-proteins).

There are more than 1000 known G protein coupled

receptors, all of which have seven transmembrane
segments that loop in and out of the cell membrane.
Fig: Components of the hormone receptor–
G protein effector system
• Receptors that couple to effectors through G proteins
typically have seven membrane-spanning domains.

• In the absence of hormone (left ), the heterotrimeric G-

protein complex (α,β,γ,) is in an inactive guanosine
diphosphate (GDP)-bound form and is probably not
associated with the receptor.

• This complex is anchored to the plasma membrane

through prenylated groups on the subunits (wavy lines )
• On binding of hormone (H) to the receptor, there is a
presumed conformational change of the receptor—as
indicated by the tilted membrane spanning domains—
and activation of the G-protein complex.

• This results from the exchange of GDP with GTP on the

subunit, after which α and βγ dissociate.

• The subunit binds to and activates the effector (E)

• E can be: adenylyl cyclase, Ca2+, Na+, K+ or Cl– channels ,

phospholipase C, or cGMP phosphodiesterase.
Mechanism of action of Group II hormones via CAMP

React with specific receptors outside the cell.

This triggers an enzyme reaction with lead to the

formation of a second messenger (cAMP).

cAMP can produce specific intracellular functions:

Activates cell enzymes
Change in membrane permeability
Promote protein synthesis
Change in cell metabolism
Stimulation of cell secretions
cAMP as a second messenger

• Cyclic AMP was the first intracellular signal

identified in mammalian cells.
• Several components comprise a system for the
generation, degradation, and action of cAMP
– Adenylyl cyclase
– Protein kinase
– Phosphoproteins
– Phosphodiesterases
– Phosphoprotein phosphatases
Hormonal shows action through cAMP-dependent protein
kinase (PKA)

•PKA exists in an inactive form as an R2C2 heterotetramer

consisting of two regulatory and two catalytic subunits.

•The cAMP generated by the action of adenylyl cyclase

binds to the regulatory (R) subunit of PKA.

• This results in dissociation of the regulatory and catalytic

subunits and activation of the catalytic subunits
• The active catalytic subunits phosphorylate a number
of target proteins on serine and threonine residues.

• Phosphatases remove phosphate from these residues

and thus terminate the physiologic response.

• A phosphodiesterase can also terminate the

response by converting cAMP to 5′-AMP
Fig: Hormonal regulation of cellular processes through
cAMP-dependent protein kinase (PKA)
 Cyclic adenosine monophosphate (cAMP) mechanism by which
many hormones exert their control of cell function

ACTH
CRH
FSL
LH
Calcitonin
TSG
hCG
PTH
Glucagon
Vasopressin( V2
Receotor, Epithelial
cells)
Angitensin-
2( epithelial cells)
Catecholamines ( beta
receptors)
2) Calcium or Phosphatidylinositols as second
messenger
Ionized calcium is an important regulator of a
variety of cellular processes, including

 Muscle contraction,
 The blood clotting cascade,
 Enzyme activity, and
 Membrane excitability
Certain hormone-receptor interactions result in the activation of
phospholipase C

Phospholipase C results in generation of

• inositol trisphosphate (IP3), which liberates stored

intracellular Ca2+, and
•diacylglycerol (DAG), a potent activator of protein kinase C (PKC).

In this scheme, the activated PKC phosphorylates specific

substrates, which then alter physiologic processes.

Likewise, the Ca2+-calmodulin complex can activate specific

kinases. These actions result in phosphorylation of substrates, and
this leads to altered physiologic responses.
Fig: Hormone-receptor interactions resulting in the
activation of phospholipase C
 list of group I and II hormones:

Group I  Steroid & Thyroid hormones

Cortisol, aldosterone, estrogen,
progesterone, testosterone and Vit. D

Group II  Peptide / Amine hormones

A  CRH, TSH, FSH, LH, ADH, Adrenaline α2
B  ANP, NO
C  TRH, Oxytocin, Adrenaline α1, CCK, Ach
D  GH, IGF, Prolactin, insulin
 Hormones secreted by hypothalamus:

• Hypothalamus is regarded as master coordinator of hormonal

action.
• In response to stimuli of CNS hypothalamus liberates certain
releasing factors or hormones.
• It produces 6 releasing factora:
• TRH, CRH, GnRH, GRH, HRIH, PRIH etc.