CHEMISTRY OF HORMONES • Antagonism
ENDOCRINOLOGY PART 2
Mechanism of hormone action
• All major hormones circulate to all tissues but
influences the activity of only those tissue cells
that have receptors for it.
• No activity if there are no receptors
• Hormones bring about their characteristic effects
by altering target cell activity.
• Synergism
o The hormone can act alone
o But with other hormones there will be
more defined action
o Glucagon+ epinephrine + cortisol
▪ The reaction is greater than the
sum of parts
▪ Increase the blood sugar to 240
• Permissiveness
o One hormone cannot function
o Together they can fully function
o Thyroid hormone
o Opposite effect
o Glucagon and insulin
THE FINAL EFFECTS OF HORMONES ACTION
1. Change the permeability of cell
membrane, accelerate the penetration
of substrates, enzymes, coenzymes into
the cell and out of cell.
2. Acting on the allosteric centers affect
the activity of enzymes (Hormones
penetrating membranes).
3. Affect the activity of enzymes through
the messengers (cAMP). (Hormones that
can not penetrate the membrane).
4. Act on the genetic apparatus of the cell
(nucleus, DNA) and promote the synthesis
of enzymes (Steroid and thyroid hormones).
How does a hormone communicate with its target cell?
• This depends on the chemical nature of
hormone and the cellular location of the
receptor.
Hormone Receptors
• are cellular proteins that bind with high affinity
to hormones & are altered in shape & function
by binding.
• Binding to hormone is noncovalent & reversible.
• Hormone binding will alter binding to other
cellular proteins & may activate any receptor
protein enzyme actions.
Kinds of hormone receptors
A) Cell surface receptors
• also called membrane receptors, transmembrane
receptors
• are embedded in the membranes of cells.
• act in cell signaling by receiving (binding
to) extracellular molecules.
• allow communication between the cell and
the extracellular space.
• Each cell-surface receptor has three main
components:
• an external ligand-binding domain (extracellular
domain)
• a hydrophobic membrane-spanning region
• an intracellular domain inside the cell.
 • Activated G-protein will interact with ion
Chanel-linked receptors: channel or enzyme in the membrane
• All G-protein linked receptors have 7
transmembrane domain
o Each receptor has their own specific
extracellular domain and G-protein
binding site
ENZYME-LINKED RECEPTORS

B)

• Bind to ligand
• Opens a channel that will allow specific ions to
pass through
• Interaction with the phospholipid FA tails that
form the center of the PM
• Many amino acids in the membrane spanning
region are actually hydrophobic

CONFORMATIONAL CHANGE • Cell surface receptors with intracellular domain

associated with enzyme
• Large extra and intra cellular domains
• Transmembrane spanning region is a single
alpha helical peptide
B) Internal receptors

• Allows ions such as sodium, calcium,

magnesium, and hydrogen
• When ligand binds, the conformational change
will happen
G PROTEIN RECEPTORS

Internal receptors are also called intracellular or

cytoplasmic receptors. They are found in the cytoplasm
of the cell and respond to hydrophobic ligand molecules
that are able to travel across the plasma membrane.
Once inside the cell, many of these molecules bind to
proteins that act as regulators of mRNA synthesis to
mediate gene expression.
Transducers
• proteins that convert the information in hormonal
signals into chemical signals understood by cellular
machinery.
• translation
EFFECTORS
• are the enzymes & other proteins that convert the
transduced hormonal signal into biochemical
changes that generate the cellular response to
hormone binding.

Can single cells make or sense more than one hormone

at a time?
Yes, cells can make multiple hormones, even of differing
chemical classes, & they can sense multiple signals -- &
integrate them -- all at once.

How do hormone levels vary?

Hormone levels rise & fall due to
• synthesis Tropic hormones
• degradation • Target other endocrine glands
• clearance • Hypothalamus
• target cell binding is just a small amount of • TRF targets pituitary
removal of hormone form circulation • Pituitary
• receptors, transducer, and effector cells can • Secretes TSH
also change based on age, sex, phyiology. • Thyroid gland
• Stimulated by TSH
Category of hormones • are important to understanding chemical
Hormones are classified according to: source and coordination.
structure
According to source Hormones according to structure

• Peptide and polypeptide hormones

o Include most hormones
o Water soluble
o Circulate freely in the blood
 o Attach to cell membrane receptors o Cross the cell membrane
▪ Activate the secondary ▪ Bind with receptors then
messenger nuclear DNA
o Short half life • Steroid hormones
o Stored in secretory glands o Derived from cholesterol
o Secreted mostly by anterior pituitary o Quickly secreted from the cell
gland o Includes:
▪ From placenta, pancreas, and ▪ Cortisol
parathyroid glands ▪ Aldosterone
o Includes: ▪ Testosterone
▪ Growth hormone ▪ Estrogen
▪ Insulin ▪ Progesterone
▪ Prolactin o Production is on as needed basis
▪ ACTH o No storage
▪ ADH o Precursors in cytoplasm
▪ PTH o Requires protein to transport in the
▪ Calcitonin blood
▪ Hypothalamic hormones • Arachidonic acid derived hormones
▪ Endorphins o Made from PUFAs
▪ Glucagon o Called eicosanoids
▪ Lipotropins o Includes:
▪ Oxytocin ▪ Prostaglandins
▪ MSH • Multiple targets
▪ Somatostatin • Raise blood pressure
▪ Thymosine • Expulsive uterine
▪ TRH contractions
• Glycoprotein hormones ▪ Prostacyclin
o Includes ▪ Leukotrienes
▪ FSH • Mediate inflammation
▪ LH ▪ Thromboxins
▪ TSH o Metabolized upond produced
o Half-lives are few minutes o Localized
o Does not bind to other proteins ▪ Also autocrine
• Amine hormones
o Derived from tyrosine Hormone control
o Includes • Regulated by stimuli
▪ T3 • Signals from nervous system [ neural]
▪ T4 • Chemical changes in the blood
▪ Epinephrine [humoral]
▪ Norepinephrine • Other hormones [ hormonal]
o Thyroid hormones are lipid soluble • Most hormonal regulation by negative feedback
▪ half-lives are a few days • Involves pituitary and hypothalamus
o Catecholamines are water soluble
▪ Half-life of few minutes
o Exert action by activating secondary
messenger system in the cell
Humoral stimuli
• Humor means various body fluids
• Secretion of hormones in direct response to
changing blood levels of certain ions and
nutrients.
• This is different from hormonal stimuli
• This is the simplest endocrine control

Neural stimuli
• In few cases, nerve fibers stimulate hormone
release.
• The classic example is response to stress, in
which sympathetic nervous system stimulates
the adrenal medulla to release catecholamines.

Hormonal stimuli
• This is best exemplified by the hypothalamic- What does concentration of circulating hormone in
pituitary-target endocrine organ blood reflect?
Rate of release

Speed at which hormone is inactivated and removed

from the body