Adrenal Gland
• Paired endocrine gland consist of two distinct parts
with different functions and embryonic origins.
• Adrenal cortex – originates from mesodermal tissue
located between the dorsal messentery of the gut and
the medial surface of the messenteric kidney.
• It synthesizes steroid hormones called corticosteroids.
• Adrenal medulla – originates from the
neuroectodermal cells from the primitive ganglia of
the celiac plexus.
• Contains chromaffin cells – synthesize and release
catecholamines, epinephrine, and norepinephrine in
response to symphathetic stimulation.
Functional Anatomy
• Adrenal glands literally “the glands next to the
kidneys” located retroperitanially in close
opposition to the kidneys.
• All domestic animals highly irrigated adrenal
glands (receiving blood from several arterial
sources).
• Main nerve supply is sympathetic nerve that
synapse with medullary cells.
• Also receive few parasympathetic fibers but little
is known about their functions.
Functional Anatomy
• Humans and other
mammals – cortex
surrounds the medulla
• Sharks – completely
separated
• Amphibians – separate but
in close contact
• Avian – intermixed
medullary and cortical
tissue and is unpaired
Functional Anatomy
• Constitute approximately 80%-90% of the mass
of the adrenal glands.
• Corticocytes – parenchymal cells of the cortex,
has a unique characteristics, and source of the
various steroid hormones
• Cytoplasm contains large number of lipid filled
droplets (most lipids are cholesterol)
• Abundant smooth ER
• Paucity of RER
• Large Golgi complexes and numerous mitochondria
• Inability to store hormones
Adrenal Cortex
• Three distinct zones.
1. Zona glomerulosa – thinnest and outermost zone
• Rumiants and humans – consist of clusters of
small and darkly stained corticocytes arranged in
whorls
• Other animals – zona arcuata, corticocytes are
grouped in the form of arcs.
• Dogs and cats – corticocytes are larger and lighter.
• Depending on the species, corticocytes appears to
be flattened or are polyhedral in outline.
• Mineralocorticoids (Aldosterone)
Adrenal Cortex
Zona glomerulosa
consists of
rounded clusters
of columnar cells
principally
secreting the
mineralcorticoid
aldosterone
• Three distinct zones.
2. Zona Fasciculata
• Middle zone and thickest of the three zones.
• Made up of cuboidal to polyhedral cell form cords
that are one cell wide and are perpendicular to the
capsule of the gland.
• Corticocytes are large with large, vesicular nuclie
and have an abundance of lipid and lipid droplets.
• Cytoplasm appears foamy and lightly stained
compared to the two adjoining zones.
• Glucocorticoids (cortisone and cortisol), and
androgens
Adrenal Cortex
Zona fasciculata,
consists of long
cords of large,
spongy-looking
cells mainly
secreting
glucocorticoids
such as cortisol
• Three distinct zones.
3. Zona Reticularis
• Innermost zone of the
adrenal cortex
• Contains small
corticocytes arranged in
a network of
anastomosing cords
• Glucocorticoids and
androgens
Adrenal Cortex
Small, better stained, arranged in a
close network and secrete mainly
sex steroids
• Composed of large, pale-staining polyhedral cells
arranged in cords or clumps and supported by a
reticular fiber network.
• Medullary parenchymal cells, known as chromaffin
cells
• Chromaffin cells of the adrenal medulla of humans
and are part of the endocrine system and an
important part of the symphathetic nervous system.
• Chromaffin cells contain enzymes for the synthesis of
norepinephrine.
• Other medullary cells contain the necessary enzymes and
co-factor to form epinephrine.
Adrenal Medulla
• Medullary chromaffin cells contain many electrondense granules, 150–350 nm in diameter, for
hormone storage and secretion.
• These granules contain one or the other of the
catecholamines, epinephrine or norepinephrine.
• Ultrastructurally the granules of epinephrinesecreting cells are less electron-dense and generally
smaller than those of norepinephrine-secreting cells.
• Norepinephrine-secreting cells are also found in
paraganglia (collections of catecholamine-secreting
cells adjacent to the autonomic ganglia) and in
various viscera.
Adrenal Medulla
• Medullary chromaffin cells are innervated by
cholinergic endings of preganglionic sympathetic
neurons, from which impulses trigger hormone
release by exocytosis.
• Epinephrine and norepinephrine are released to
the blood in large quantities during intense
emotional reactions, such as fright, and produce
vasoconstriction, increased blood pressure,
changes in heart rate, and metabolic effects such
as elevated blood glucose.
Adrenal Medulla
• These effects facilitate various defensive
reactions to the stressor (the fight-or-flight
response).
• During normal activity, the adrenal medulla
continuously secretes small quantities of the
hormones.
• The conversion of norepinephrine to epinephrine
(adrenalin) occurs only in chromaffin cells of the
adrenal medulla.
• About 80% of the catecholamine secreted from
the adrenal is epinephrine.
Adrenal Medulla
The micrograph
shows they are large
pale-staining cells,
arranged in cords
interspersed with
wide capillaries.
Faintly stained
cytoplasmic
granules can be seen
in most chromaffin
cells. X200. H&E.
EM reveals that the granules of
norepinephrine-secreting cells
(NE) are more electron-dense
than those of cells secreting
epinephrine (E), which is a
function of the chromogranins
to which the catecholamines
are bound in the granules.
Most of the hormone produced
is epinephrine, which is only
made in the adrenal medulla.
• Adrenal steroids (four major types)
• Glucocorticoids
• Cortisol
• Corticosterone
• Mineralocorticoids
• Aldosterone
• Androgens
• Dehydroepiandrosterone
• Androstenedion
• Estrogens
• Estradiol-17ß
Hormones of the Adrenal Cortex
BIOSYNTHESIS OF
STEROID HORMONES
• Begins with cholesterol, (parent compound).
• Corticosteroids are formed primarily from absorbed
cholesterol.
• Remainder is formed from acetate from the
corticocytes.
• Cholesterol it is transported to the adrenal cortical
cells by low density lipoproteins
• After LDL bind to the membrane of steroidonic cells,
the LDL-receptor complexes are internalized by
receptor-mediated endocytosis.
• In the cell LDL receptor dissociates and the receptor
is re-incorporated to the cell membrane
Biosynthesis
• LDL is catabolized and cholesterol is liberated
(this intracellular cholesterol maybe used directly
for steroidogenesis or sterified and stored in lipid
droplets.)
• Enzymes for steroidogenesis are located in the
mitochondria and endoplasmic reticulum.
• The final steroid pruduct diffuse from the
corticytes into the circulations.
• Steroids are not stored in the cells of the adrenal
cortex.
Biosynthesis
• Steroids are secreted by the adrenal glands enter
the blood stream as non-polar molecules that are
insoluble in water.
• 60%-95%, of adrenal steroids released into the
circulation are recessively bound to blood
proteins.
• Transcotin – glucocorticoids and mineralocorticoids
• Albumin – progestagens
• Sex hormone binding globulin – androgens and
estrogens
Transport
• Only free or unbound steroids passively
diffuse through the lipid bilayer of the cell
membrane of the target cells to illicit
biological effect.
• Half life of cortisol is less than 2 hours,
considerably longer than that of the
chatechyolamines release from chromaffin
cells of the adrenal medulla.
Metabolism
• Vast majority of steroids are degraded in the liver
while the remainder is degraded in the kidneys,
• Process of degradation of corticosteroids undergo
various reductions, oxidations and hydroxylation
before conjugation with glucoronic acid or
sulphates.
• The conjugated metabolites are water water
soluble which facilitates excretion.
• 75% excretes in the urine and 25% into the SI as
a component of bile.
Elimination
• Steroids hormones exert their effects by binding
to and activating hormone-specific receptors in
target cells.
• Glucocorticoids and mineralocorticoids enter
cells by diffusion and bind to hormone-specific
receptors in the cytoplasm of the target cells to
induce a conformational change in the receptor.
• In the nucleus, dimers are activated hormonereceptor complex with a high affinity to specific
DNA binding sites to direct gene transcription.
Mechanism of Action
• After transcription and synthesis of
biologically active mRNA hormoneinduced proteins elicit the steroid-specific
actions or functions in the target cells.
• Once the hormone-receptor complex has
interacted with the gene, the receptor is
recycled as inactive receptor and the
steroid hormone passively diffuses from
the cell
Mechanism of Action
GLUCOCORTICOIDS
• Cortisol (very potent, accounts for about 95 per cent of
all glucocorticoid activity)
• Corticosterone (provides about 4 per cent of total
glucocorticoid activity, but much less potent than
cortisol)
• Cortisone (synthetic, almost as potent as cortisol)
• Prednisone (synthetic, four times as potent as cortisol)
• Methylprednisone (synthetic, five times as potent as
cortisol)
• Dexamethasone (synthetic, 30 times as potent as
cortisol)
Glucocorticoids
• Cortisol and corticosterone – principal
glucocorticoids
• Cortisol predominates in humans, horses, pigs,
sheep, dogs and cats.
• Corticosterone predominates in rabbit, mouse and
rat.
• New born calf – cortisol is the major secretory
product and corticosterone does not appear until 10
days after birth.
• Adult cattle – secretes significant amounts of both
glucocorticoids.
Glucocorticoids
• Approximate ratio of cortisol and
corticosterone in adrenal venous blood of
some mammals.
•
•
•
•
•
Bovine – 0.05:1 to 1:1
Sheep – 15:1 to 20:1
Dogs – 2:1 to 5:1
Humans and cats – 5:1 to 10:1
Rats and rabbits – 0.05:1
Glucocorticoids
• Dogs and cat do not have circadian rhythm in
the secretion.
• Diurnal animals (pigs, sheep, and horses) have
several higher of secretion during the early day
hours than in last hours of day hours.
• Nocturnal animals (mice and rats) higher level
of secretions during early hours of darkness
than during the waning hours of darkness
Glucocorticoids (Daily
Rhythms)
• Stimulation of Gluconeogenesis
• Cortisol increases the enzymes required to convert
amino acids into glucose in the liver cells.
• Results from the effect of the glucocorticoids to
activate DNA transcription in the liver cell nuclei
• Cortisol causes mobilization of amino acids from the
extrahepatic tissues mainly from muscle.
• result, more amino acids become available in the
plasma to enter into the gluconeogenesis process of
the liver and thereby to promote the formation of
glucose.
Effects of Cortisol on
Carbohydrate Metabolism
• Decreased Glucose Utilization by Cells
• Causes a moderate decrease in the rate of glucose
utilization by most cells in the body
• Elevated Blood Glucose Concentration and
“Adrenal Diabetes.”
• Increase gluconeogenesis and reduction in the rate of
glucose utilization cause the blood glucose to rise and
timulates secretion of insulin
• Increased plasma levels of insulin, however, are not as
effective in maintaining plasma glucose as they are
under normal conditions
Effects of Cortisol on
Carbohydrate Metabolism
• Reduction in Cellular Protein
• Caused by both decreased protein synthesis and
increased catabolism of protein already in the cells.
• Effects may result from decreased amino acid
transport into extrahepatic tissues
• Cortisol Increases Liver and Plasma Proteins
• results from a possible effect of cortisol to enhance
amino acid transport into liver cells (but not into
most other cells) and to enhance the liver enzymes
required for protein synthesis.
Effects of Cortisol on Protein
Metabolism
• Increased Blood Amino Acids, Diminished Transport
of Amino Acids into Extrahepatic Cells, and Enhanced
Transport into Hepatic Cells.
Effects
• Increased rate of deamination of amino acids by the
liver
• Increased protein synthesis in the liver,
• increased formation of plasma proteins by the liver,
and
• Increased conversion of amino acids to glucose-that is,
enhanced gluconeogenesis.
Effects of Cortisol on Protein
Metabolism
• Mobilization of Fatty Acids
• Promotes mobilization of fatty acids from adipose
tissue that increases the concentration of free fatty
acids in the plasma, which also increases their
utilization for energy
• Have a direct effect to enhance the oxidation of fatty
acids in the cells.
• Neutral fats make up the largest pool of energy in the
body.
Effects of Cortisol on Fat
Metabolism
• Increased mobilization of fats by cortisol,
oxidation of fatty acids helps shift the metabolic
systems of the cells from utilization of glucose for
energy to utilization of fatty acids in times of
starvation or other stresses.
• Glucocorticoids permissively enhance the actions
of glucagon, epinephrine, and growth hormone in
mobilization of fatty acids.
• It promotes food intake by stimulating the appetite
center of the hypothalamus.
Effects of Cortisol on Fat
Metabolism
• Endocrine System
• GCC antagonize the effect of insulin in
muscles, adipose tissue and the liver.
• Enhances the effect of glucagon and
epinephrine on intermediary metabolism
• Induces hyperglycema and hyperinsulinemia which
leads to diabetis mellitus in dogs.
Systemic Effects
• Musculoskeletal System
• Hypersecretion of GCC stunts growth of young
animals
• Wasting or atrophy of muscle tissue in adult
animals (catabolic effect on muscle protein)
• Bone mass can also be lost (decrease osteoblast
activity and inhibition of collagen synthesis)
• Antagonizes action of Vit. D (absorption of
calcium in the intestines)
Systemic Effects
• Skin and Connective Tissue
• Modulate the proliferation and differentiation
of fribroblasts (maintenance of skin and
connective tissue).
• Thinning of skin and subcutis
• Hypersecretion of GCC leads to
hyperpigmentation, pyoderma, seborrhea, and
atrophy of hair follicle and loss of hair.
Systemic Effects
• Cardiovascular System
• Maintenance of normal vascular tone and
blood pressure.
• Enhance vascular response to vasoactive
agents (catecholamines, angiotensins and
vasopressin)
• GCC enhances the activity of Na, K, ATPases
in cardiocytes.
• Increase force of contraction and increase
rate of contraction
Systemic Effects
• Renal System
• GCC impairs the ability of the kidney to
excrete a load of water
• Lead to decrease rate of GFR and increase in
vasopressin.
• High GCC causes increase absorption of Na
excretion of K.
• Increase blood flow to the kidneys (direct
vasodilatory effect on renal vessels)
Systemic Effects
CORTISOL IS IMPORTANT IN
RESISTING
STRESS AND INFLAMMATION
• Stress that increase cortisol release
•
•
•
•
•
•
•
•
Trauma of almost any type
Infection
Intense heat or cold
Injection of norepinephrine and other
sympathomimetic drugs
Surgery
Injection of necrotizing substances beneath the
skin
Restraining an animal so that it cannot move
Almost any debilitating disease
• Cortisol has two basic antiinflammatory
effects:
• it can block the early stages of the
inflammation process before inflammation
even begins, or
• if inflammation has already begun, it causes
rapid resolution of the inflammation and
increased rapidity of healing.
Anti-inflammatory Effects of High
Levels of Cortisol
• Cortisol stabilizes the lysosomal membranes
• Most important anti-inflammatory effects
• Proteolytic enzymes which are mainly stored in
the lysosomes, are released in greatly decreased
quantity.
• Cortisol decreases the permeability of the
capillaries
• Prevents loss of plasma into the tissues
• Reduces migration of white blood cells into
inflamed area.
Cortisol Effects in Preventing
Inflammation
• Cortisol decreases both migration of
white blood cells into the inflamed area
and phagocytosis of the damaged cells.
• diminishes the formation of prostaglandins and
leukotrienes that otherwise would increase
vasodilation, capillary permeability, and
mobility of white blood cells.
Cortisol Effects in Preventing
Inflammation
• Cortisol suppresses the immune system, causing
lymphocyte reproduction to decrease markedly.
• T lymphocytes are especially suppressed
• Reduced amounts of T cells and antibodies in the inflamed
area lessen the tissue reactions that would otherwise
promote the inflammation process.
• Cortisol attenuates fever mainly because it
reduces the release of interleukin-1 from the white
blood cells.
• principal excitants to the hypothalamic temperature control
system. The decreased temperature in turn reduces the
degree of vasodilation.
Cortisol Effects in Preventing
Inflammation
• Perhaps, results from the mobilization of amino
acids and use of these to repair the damaged
tissues
• Perhaps it results from the increased glucogenesis
that makes extra glucose available in critical
metabolic systems
• Perhaps it results from increased amounts of fatty
acids available for cellular energy
• Perhaps it depends on some effect of cortisol for
inactivating or removing inflammatory products.
Cortisol Causes Resolution of
Inflammation
• Anti-growth Effect
• Inhibit GH secretion (somatic growth), will
result to muscle atrophy and muscular weakness
• Poor wound healing, decrease fibroblast
proliferation and decrease connective tissue
strength andquality
• Inhibition of Vit. D metobolites (osteoporosis)
• Inhibition of calcium absorption in the gut
• Increased collagen degradation
• Inhibit collagen mitosis (inhibition of Vti. D)
Other Effects
• Exerts its effects by first interacting with intracellular
receptors in target cells.
• Cortisol binds with its protein receptor in the
cytoplasm
• Hormone-receptor complex then interacts with
specific regulatory DNA sequences (glucocorticoids
response element) to induce or repress transcription.
• Increase or decrease transcription of many genes to
alter synthesis of mRNA for the proteins that mediate
their multiple physiologic effects.
Cellular Mechanism of
Cortisol Action
Regulation of GCC secretion
MINERALOCORTICOIDS
• Aldosterone (very potent, accounts for about
90 percent of all mineralocorticoid activity)
• Desoxycorticosterone (1/30 as potent as
aldosterone, but very small quantities
secreted)
• Corticosterone (slight mineralocorticoid
activity)
• 9a-Fluorocortisol (synthetic, slightly more
potent than aldosterone)
Mineralocorticoids
• Regulate the concentration of sodium and
potassium in the exrtracellular fluid
• Increasing renal uptake of sodium
• Stimulating the excretion of potassium in the
urine.
• Stimuli fro secretion
• Changes in electrolyte level and water balance
Mineralocorticoids
• Most potent mineralocorticoids and release from
zona glumerulosa
• Affinity to blood proteins is relatively low
• 50% loosely bound to albumin
• 40% unbound
• 10% bound to transcortin
• Action is not evident untill 15 – 30 minutes after
administration.
• Major targets are the epithelial cells of the
collecting tubules of the kidneys.
Aldosterone
• Increases the activity of Na+ -K+ ATPases or
Na + -K + pumps
• Cause reabsorption of of Na+ from the fluid of
the renal tubules and excretion of K+ and H +
into the urine.
• Increases the activity of Na+ -K+ ATPases in
the epithelial cells of the sweat glands,
stomach, colon, and ducts of the salivary
glands.
• Reabsorption of Na+ and excretion of K+ and
H+
Aldosterone
• Altered by circadian rythms (synchronized with
sleep-wake cycle)
• Diurnal animals – high in the morning than in the
evening
• Nocturnal animals – higher during in the early hours of
darkness than waning hours of darkness
• Dogs – not exhibit a daily rhythm in the secretion.
• Two important Factors
• Renin-angiotensin System
• Changes in extracellular concentrations of Na+- K+.
Regulation of Mineralocorticoid
Secretion
• Factors that influences the secretion of
renin
• Low levels of Na (monitored by cell of the
macula densa)
• Synthesis and release of glucocorticoids –
increase reabsorption of Na and H2O by
kidney tubules – lead to increase in blood
volume and blood pressure
• Blood volume (monitored by cells of the
juxtaglumerular apparatus)
Regulation of Mineralocorticoid
Secretion
• Factors that influences the secretion of
renin
• Blood pressure (monitored by cells of the
juxtaglumerular apparatus)
• Decrease BP in the afferent arterioles of renal
glumeruli – ilicit an increases of secretion of
renin
• Sympathetic nerve activity
Regulation of Mineralocorticoid
Secretion
• Inhibitory Factors
•
•
•
•
Increase in sodium levels
Increase blood volume
Increase blood pressure
Angiotensins and vasopressins
Regulation of Mineralocorticoid
Secretion
• Hyperadrenocorticism
• Characterized by development of peculiar
redistribution of body fat and have a pot
bellied appearance.
• One of the most common endocrine diseases in
dog
• Occasionally in cats, rare in horses and other
species
Dysfunctions of the Adrenal
Cortex
• Types of Hyperadrenocorticism
1. Primary Hyperadrenocorticism
• Accounts for ~15% of all cases of naturally
occurring hyperadrenocorticism in dogs
• Caused by adenomas or carcinomas of the
adrenal cortex
• 20% in cats is caused by neaplasms
• Parvocellular neurons and pituitary
corticotropes are atropied due to inhibitory
effects of glucocorticoids.
Hyperadrenocorticism
• Types of Hyperadrenocorticism
2. Secondary Hyperadrenocorticism
• Accounts for 85% of the cases of naturally
occurring hyperadrenocorticism in dogs,
• 90% is caused by ACTH producing neoplasms
of the pars distalis or the pars intermedia.
• 10% hyperplasia and hypertrophy ACTH
producing cells (pars distalis or the pars
intermedia)
• Horses – neoplasia of the pars intermedia
Hyperadrenocorticism
• Types of Hyperadrenocorticism
3. Iatrogenic/Pharmacological
Hyperadrenocorticism
• Occurs because of widespread use of synthetic longacting glucocorticoids.
• Long-acting glucocorticoids can lead to iatrogenic
hyperadrenocorticism, followed by
hypoadrenocorticism.
• Parvocellular neurons and pituitary corticotropes are
atropied in animals affected by the prolonged treatment
with natural or synthetic glucorcorticoids
Hyperadrenocorticism
2 types
• Primary Hyporadrenocorticism
• Most common form and naturally occurring
accounting to nearly all cases of the disease
• Characterized by deficiency in the secretion of
both glucocorticoids and mineralocorticoids.
• Associated with atrophy or destruction of the
zona fasciculata and zona reticularis and less
frequently, atrophy or degeneration of the 3
zones
Hyporadrenocorticism
2 types
• Secondary Hyporadrenocorticism
• Naturally occurring are rare in domestic
species
• Associated with hyposecretion of ACTH from
the pituitary.
• Atrophy of the zona fasciculata and zona
reticularis which results to glucocorticoid
deficiency.
Hyporadrenocorticism
CATECHOLAMINES
• Secreted in the adrenal medulla and referred to as
the emergency hormone.
• Released by activation of fight or flight
mechanism.
• (cold, apnea, and hypoglycemia)
• Constitutes the principal regulatory mechanism
to elicit the sympathetic responses that allow
animal to meet physical demands and responds to
life threatening challenges.
Catecholamines
• Synthesize from tyrosine by chromaffin cells by
adrenergic and dopaminergic neurons
• Tyrosine is absorbed directly from the blood into
the cytosol of the chromaffin cells and hydrolyze
to 3,4-dihydroxypenylalanine (DOPA).
• DOPA is the decarboxylated into the cytosol to
form dopamine.
• After transport to the granules of chromaffin cells
by an active process.
Biosynthesis of
Cathecolamines
• Dopamine is converted into norepinephrine by ßhydroxylase.
• In chromaffin cells devoid of phenylethanolamine Nmethyltransferase noirepinephrine is stored in granules
until it is secreted from the cell.
• Mammals also contain cells that have
phenylethanolamine N-methyltransferase
noirepinephrine in the cytosol.
• Norepinephrine is released into the cytosol where
cofactor S-adenosylmethionine serves as a methy
donor for the synthesis of the epinephrine that is then
stored in secretory granules for release into the
circulation
• Catecholamines are stored in secretory
granules in adrenomedullary cells and
dopaminergic and adrenergic neurons
throughout the body.
• Mammals –adrenal medulla is the primary
source of epinephrine
• Chromaffin cells and adrenergic neurons –
norepinephrine synthesizing cells
Storage of Cathecolamines
• Calcium and energy in the form of ATP are
required for the release of catecholamines.
• Release of acetylcholine from preganglionic nerve will
stimulate chromaffin cell and postganglionic
sympathetic nerve endings causing depolarization of
plasma membrane and a concumitant influx of Ca2+
into the cell.
• In the adrenal medulla, membranes of the
catecholamine-containing granules fuse with the
plasma membrane of the chromaffin cell and the
contents of the granules are expelled by exocytosis
Release and Fate of
Catecholamines
• Norepinephrine and epinephrine release in
adult animals is not constant.
• Anxiety and hypoxia – more norepinephrine
than epinephrine
• Hypoglycemia and activation of flight and
fight mechanism - more epinephrine than
norepinephrine
Release and Fate of
Catecholamines
• Degradation occurs largely in the kidneys and liver
• (combined actions of catechol-ortho-methyl transferase in
the cytosol and the mitochondrial enzyme monoamine
oxidase).
• Catabolism of catecholamines
• Ortho-methylation followed by deamination of intermediate
metabolites
• Deamination followed by ortho-methylationof intermediate
metabolites
• Most conjugated metabolites are excreted in the urine and
bile
Release and Fate of
Catecholamines
• Adrenergic Receptors
α Receptors
• Both NE and E bind to this
• Mostly excitatory except inhibition of GIT motility
• α1 subtypes
• found in postsynaptic receptors
• Contraction effect on vascular and other smooth
muscles
• α2 subtypes
• affect pre-synaptic terminal
• Inhibit release of CAT’s
Catecholamine Receptors
• Adrenergic Receptors
ß Receptors
• Mostly inhibitory except excitation of
myocardium
• ß1 subtypes
• Mediates direct cardiac effects
• ß2 subtypes
• Mainly smooth muscle relaxation (vascular,
bronchial, uterine); mediates metabolic effects
Catecholamine Receptors
• Dopaminergic Receptors
D1 Receptors
• Mediate dilatation of the vascular bed of the heart
kidneys, mesentery and cerebrum.
• Mediate the release of parathyroid hormones in cattle
and possible in other domestic animals.
D2 Receptors
• Inhibit secretion of aldosterone, prolactin, and renin
• May causes emesis or vomiting in humans and
animals
• Inhibit release of norepinephrine into the synaptic cleft.
Catecholamine Receptors
• Hormone binding properties of receptors
• Changes which affect the target cells or tissues due to
the effect of hormone itself (homologous regulation)
• Changes in the receptor mediated responses of target
cells due to other hormones (heterologous regulation)
• Receptor concentration
• Down regulation (decreased concentration)
• Up regulation (increased concentration)
• Receptor signalling
• Post-receptor alterations
Regulation of Catecholamine
• Activation of α1 receptors increase the release of Ca2+
from intracellular storage site
• Activation of α2 increases the influx of Ca2+ from
extracellular fluid
• Inhibition of adenyl cyclase in some cells such as ß
cells of the pancreas, adipocytes and adrenergic nerve
endings
• Activation of ß1 and ß2 increase in adenyl cyclase activity
• Activation of D1 receptors activates adenly cyclase andc
incerease cAMP levels
• Activation of D2 receptors causes inhibition of adenly
cyclase
Mechanism of Action
Central Nervous System
Epinephrine
Norepinephrine
• Anxiety, fatigue and
restlessness
• Favor the release of
ACTH, TSH, and
gonadotropins
• Increase output of ACTH
and TSH in an emergency
situation.
• No effect
Effects of Catecholamines
Cardiovascular System
Epinephrine
Norepinephrine
• Increase BP (systolic
pressure)
• Tachycardia
• Coronary dilatation
• Vasoconstriction of skin and
mucous membranes
• Clow down the absorption
of anesthetics (subcutneous
vasoconstriction)
• Increase BP (systolic and
diastolic)
• Bradychardia
• Coronary dilatation
• Vasoconstriction of skin
and mucous membranes
• Hypertensive agent
• Prevent hypotension in
prolonged surgery
Effects of Catecholamines
Respiratory System
Epinephrine
Norepinephrine
• Brief period of apnea due
to elevated BP acting on
carotid artery and direct
inhibitory effect on the
respiratory center
• Increased respiratory
depth and rate (CNS
stimulation)
• Same effect
Effects of Catecholamines
Muscular System
Epinephrine
Norepinephrine
• Constriction of smooth
muscle
• Relaxes the body of the
urinary bladder
• Constriction of the neck of
the bladder
• Direct inhibition (ß1) and
indirect inhibition (α1) of
contraction of the GIT
smooth muscle
• Constriction of smooth
muscle
• Constriction of the neck
of the bladder
• Direct inhibition (ß1) and
indirect inhibition (α1)
contraction of the GIT
smooth muscle
Effects of Catecholamines
Metabolism
Epinephrine
Norepinephrine
• Glycogenolysis in the
liver and muscle of dogs
and other animals
• Increase the release of
insulin and glucagon (ß2)
• Decrease insulin release
(α1)
• Same effect
Effects of Catecholamines
• Hyperfunction of the adrenal medulla
• Red brown tumors arise from the chromaffin
cells
• Catecholamines are being produced constantly
or episodically
• May also produce various peptides hormones
including ACTH, calsitonin and somatostatin
• Rare and observed in dogs, cats and horses
Pheochromocytomas
End…
• 1. What do you call the parenchymal cell
of the adrenal cortex?
• Give the 3 layers of the adenal cortex, 2-4;
and hormones they secretes, 5-7.
• 8. What do you call parenchymal cell of
the medullary?
• 9-10. Hormones secreted by the adrenal
medulla.
• 11-13. 3 types of carrier (blood) proteins
Q#4…
• 14-15. 2 glucocorticoid hormones
• 16. The most potent mineralocorticoids
• 17. What is the primary source of epinephrine in
mammals?
• 18-19. Diseases that results from dysfunction of
the adrenal cortex.
• 20. What is the rare tumors that may arise from the
adrenal medulla that causes catecholamines to be
produced constantly or episodically.
Q#4…