Hormones

Samreen Tanveer
 Hormones
• Hormones are chemical substances that coordinate numerous metabolic
processes of our body.
• The intracellular communication is principally through extracellular
signaling molecules termed as hormones.
Classification based on chemical structure

Hormones are categorized into two classes on the basis of chemical

structure:
• Protein hormones are precursors of either peptides or polypeptides. For
example insulin, Pituitary gonadotrophins, Thyrotrphin-releasing
hormone.
• Steroid hormones are cholesterol derivatives. For example estrogen,
testosterone, aldosterone etc
 Classification

Protein Hormones Steroid Hormones

 Insulin  Progesterone

 Glucagon  Cortisol

 Oxytocin  Aldosterone

 Vasopressin  Testosterone
 Estrogen
 INSULN
• Insulin is secreted by beta cells of “Islets of Langerhans” in pancreas for
regulation of blood glucose level.
• Patients having malfunctioning or degeneration of beta cells need to
administer insulin intravenously for regulation of blood glucose level.
Insulin is obtained biosynthetically from Escherichia Coli through
recombinant DNA technology and semisynthetically from porcine.
 Chemistry
• Human insulin (Mol. mass 5808 Daltons) is composed
of 51 amino acids.
• Its chemical structure is having two chains A and chain
B that are linked together by disulphide linkages
between two cysteine amino acid residues.
• A connecting peptide C chain that held the two chains
together is present in the insulin structure when it is in
inactive form called proinsulin.
• Pepteide C is cleaved to attain the active form of insulin.
It can exist as hexamer, dimer and monomer forms.
Monomer is the biologically active form of insulin.
 Structure activity relationship
• Disulphide bridges between the cysteine residues are necessary for the activity of
insulin. Three disulphide bridges are present in insulin. Two disulphide bridges are
connecting chain A and chain B. While the third disulphide bridge is intra disulphide
linkage of chain A.
• A peptide C chain of amino acids is prerequisite for insulin structure in prounsulin
form. It connects the chain A and B and is isolated in order to attain the active form of
insulin.
• Removal of amino acids from B1 to B4 (Chain B) reduce 30% activity. Removal of
Leucine (B6) from insulin results in less than 1% activity.
 Structure activity relationship
• Insulin exists mainly as a monomer at its low blood concentrations (~10 -6 M)
It can form dimer at increased concentrations at pH 7.0. Dimer of insulin in
held so by the intermolecular hydrogen bonding of C terminal of each Chain B.
• Moreover insulin may self assembled in hexameric complexes in zinc ions
presence at its increased concentrations. Insulin hexamer constitutes three
dimers and with two zinc ions present at central axis The self assembly of
insulin in dimer and hexamer is meant for stabilization in storage as well as
serves as a reserve. When blood glucose level is raised these hexamers and
dimers dissociate to monomeric forms for receptor binding.
 Biological action
• Decreased Gluconeogenesis and Increased glycogenesis. Scaling down blood sugar by
increasing cellular uptake of glucose in adipose tissue and muscles cells. Consequently
followed by conversion into glycogen. Thereby reducing the lipolysis.
• Protein synthesis. Insulin prompts the movement of serum potassium and amino acids
uptake into the cells. Insulin modulates the utilization of body carbohydrates and augments
protein synthesis.
• Regulation of enzyme activity of pyruvate dehydrogenase and membrane-bounded
lipoprotein lipase.
 GLUCAGON
• Glucagon is secreted by alpha cells of islets of langerhans in pancreas.
Glucagon (molar mass of 3485 Daltons) is composed of 29 amino acids.
Glucagon and insulin work in coordination for regulation of blood glucose
level. In response to decreased blood glucose, glucagon is released and
stimulates the conversion of stored glycogen (stored in the liver) to
glucose, which can be released into the bloodstream.
• This process is called glycogenolysis.
GLUCAGON
 Structure activity relationship
According to SAR studies
• Positions 10 (tyrosine), 15 (aspartic acid) and 16 (serine) in the amino
acid sequence is essential for activity and receptor bibding.
• In addition, N-terminal histidine is also essential for its binding to the
receptor.
• he amino acid sequences for the C-terminal half of also contribute to its
binding to the receptor, although they are less important compared with
those of the N-terminal half
 Biological actions
• Glycogenolysis
• Activation of gluconeogenesis
• Inhibition of Glucose oxidation.
• Increased ketogenesis
 VASOPRESSIN
• Antidiuretic hormone or vasopressin is secreted by hypothalamus and stored
& released by posterior pituitary. It is necessary for maintaining plasma
osmolality. Blood osmolality is actually the concentration of dissolved
particles present in it.
• Blood particles refer to electrolytes that maintain blood pH. When water
volume is increased in extracellular fluid, concentration of blood particles
decreases. In the same way, lesser the water more is the concentration of
particles. Thus blood osmolality is increased when we are dehydrated and
decreased when we are over hydrated or our body fluid buildup.
 Chemistry

• Vasopressin, a nonapeptide
weighs 1084 Daltons. Its
structure consists of one
disulphide bridge. At 8th
position arginine is present.
That’s why it is also called as
argipressin or arginine
vasopressin.
 Structure activity relationship
• Vasopressin molecule consists of nine amino acid residues. At 8 th position
arginine is present. The only difference of vasopressin expressed in pigs to
that of humans is of arginine moiety. In pigs the vasopressin peptide contains
lysine in place of arginine. Any missequencing in the peptide formation
results in loss of peptide activity.
 Structure activity relationship
• Two analogues of vasopressin are reported that are more promising than
vasopressin, Terlipressin and desmopressin.
• Terlipressin structure contains lysine in 8th position of peptide instead of
arginine.
 Structure activity relationship
• In Desmopressin structure cysteine residue is deaminated. Moreover
dextro-stereoisomer of arginine is substituted to protect it from rapid
degradation by endothelial peptidases. Thus its action lasts for 6-14 hours.
 Biological action
• Vasopressin exhibits its action by two types of receptors:
• V1 receptors are located on renal collecting ducts. It function is to increased
water permeability. It results in decreased urine formation. Consequently blood
volume and arterial pressure is increased.
• V2 receptors are located on smooth muscle. Activation of these receptors
results in vasoconstriction. It results in increased arterial pressure.
• Vasopressin shows its action through osmoreceptors located in hypothalamus.
This in turn regulates the vasopressin secretion in hypoosmolality of blood.
 OXYTOCIN
• Oxytocin is produced in hypothalamus and secreted by neurohypophysis
(posterior pituitary gland).
 Chemistry
• It is also a nonapeptide having molecular mass of 1007 Daltons. It differs
from vasopressin in amino acid sequence at position 3rd and 8th. At
position 3 it contains isoleucine instead of phenylalanine. While at 8 th
position oxytocin contains leucine instead of arginine. There is one
disulphide bridge present in the structure of oxytocin
 Structure activity relationship
• Amino acid sequence is crucial for the activity of oxytocin because
vasopressin and oxytocin differ by two amino acid residues at position 3
and 8 as mentioned above.
• If the disulphide linkage is break the peptide activity will be lost.
• Deamination of Cysteine residues will also lead to loss of activity.
 Biological action
• Oxytocin play key role in female reproduction:
• It is secreted during child delivery or labor
• Thus it facilitates child birth and breastfeeding.
• Pitocin, synthetic analogue of oxytocin is also manufactured and utilized for inducing labor.
• Natural labor involves the release of endogenous opioid termed as beta-endorphins. These
are produced in hypothalamus; its release significantly rises throughout labor till the time of
child birth. Beta-endorphins modulate oxytocin release and assist block pain to control the
labor speed and intensity. While in case of pitocin infusion beta-endorphins are not released.