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The Adrenal Glands
Chapter 14
Adrenal gland
The outer cortex (80%) releases steroids; the
inner medulla (20%) releases catecholamines.
Pyramid
shape
Adrenal
gland
No direct physical connection
kidney
Zona
glomerulosa
Cortex
Zona
fasciculata
Zona
reticularis
Capsule
Medulla
fig 14-1, pg 434
Slide 2
Adrenal cortex
Based on the arrangement of cells
under a microscope, the adrenal cortex
can be divided into three different
zones.
Glomerulosa =
mineralocorticoids
Fasciculata =
glucocorticoids
Reticularis =
androgens
Slide 3
Circadian
rhythms
Stress
“Hypothalamicpituitary-adrenal axis”
Hypothalamus
CRH
Anterior
pituitary
ACTH
hypothalamus : CRH
pituitary : ACTH 
adrenal cortex:
promoting the growth
of adrenal cortex,
control of
glucocorticoid
Cortisol
Adrenal
cortex
fig 14-3, pg 436
Slide 4
Three steroids are the primary products of
the adrenal cortex.
Cortisol (glucocorticoid),
Aldosterone (mineralocorticoid)
DHEA (weak androgen, converted to
testosterone in peripheral tissue)
Cortisol
(glucocorticoid)
Aldosterone
(mineralocorticoid)
Dehydroepiandrosterone
(androgen)
Slide 5
Cholesterol
Pregnenolone
Progesterone
Zona glomerulosa
Each cell makes
steroids according
to the enzymes it
has.
Corticosterone
Aldosterone
Cholesterol
Pregnenolone
17-OH-Pregnenolone
Zona fasciculata
17-OH-Progesterone
“Steroid hormones are
synthesized and
secreted on demand
and are not stored”
Cortisol
Cholesterol
Pregnenolone
Zona reticularis
17-OH-Pregnenolone
Dehydroepiandrosterone
fig 14-5, pg 437
Slide 6
Ratelimiting
step;
(LDL)
thus is the
primary
site of
regulation
of steroid
synthesis
Slide 7
Control of Glucocorticoid
Circadian
rhythms
Stress
Cortisol is produced in the
greatest amount in adrenal
cortex
Hypothalamus
CRH
Anterior
pituitary
ACTH
Two type of stimuli
1. Circardian
rhythm
2. Increased
secretion in
response to a
variety of
specific stimuli
Cortisol
Adrenal
cortex
fig 14-3, pg 436 Slide 8
Control of Glucocorticoid
Circadian
rhythms
Stress
Hypothalamus
CRH
Anterior
pituitary
ACTH
Two type of stimuli
1. Circardian
rhythm
2. Increased
secretion in
response to a
variety of
specific stimuli
Cortisol
Adrenal
cortex
fig 14-3, pg 436 Slide 9
Circadian rhythm of Glucocortcoids
Sleep-wake pattern  hypothalamic pituitary system
CRH, ACTH,
cortisol show
circadian
sleep-wake
rhythm, with
peak at
awakening.
Sleep
Midnight
AM
Time of Day
PM
fig 14-7, pg 438
Slide 10
Stress-induced glucocorticoid secretion
Slide 11
Negative feedback in glucocorticoid secretion
Circadian
rhythms
Stress
Hypothalamus
CRH
ACTH reduces
CRH secretion
Cortisol decreases
the activity of CRHproducing neurons
Anterior
pituitary
ACTH
Cortisol
Adrenal
cortex
Cortisol decrease the
sensitivity of
corticotropes to CRH
fig 14-3, pg 436
Slide 12
Transport of Cortisol in the Blood
- Corticosteroid-binding globulin (80%)
- Albumin (15%)
- Free active (5%)
Slide 13
Physiological Effects of Glucocorticoids
Cortisol  enable us to survive the
potentially damaging effects of wide
fluctuation in environment as well as
a lot of noxious factors
Ex) even a modest fasting would not be
possible without cortisol
Slide 14
Physiological Effects of Glucocorticoids
Cortisol  nuclear receptors  DNA 
altered transcription  altered
protein synthesis.
Slide 15
Physiological Effects of Glucocorticoids
Cortisol exerts its primary effects on three
different tissues in the body
1) Liver
2) Skeletal muscle
3) Adipose tissue
Slide 16
Cortisol accelerates liver urea cycle and
amino acid conversion to glucose.
Plasma
Amino
acids
Liver
Amino acid
metabolizing Ammonia
enzymes
Gluconeogenesis
Glucose
Glycogen
synthesis
Urea
cycle
Urea
Cortisol
increases the activity of
enzymes involved
fig 14-8, pg 439 Slide 17
In muscle, cortisol decreases protein
(1) decreases muscle protein synthesis;
(2) increases degradation of protein and amino acid release.
Plasma
•Anabolic steroids
; increase muscle mass
; androgens
(catabolic steroid)
Cortisol
Liver
Amino
acids
Muscle
protein
Gluconeogenesis
Cortisol
Glucose synthesis
Net transfer of amino acid
Increased blood glucose
fig 14-9, pg 440
Slide 18
Cortisol in Adipose Tissue
- Cortisol decreases adipose glucose uptake
(anti-insulin) and increases lipolysis.
- differential sensitivity of adipose tissue:
Hypersecretion of cortisol  redistribution of the
body fat
Slide 19
Other effects of cortisol
Permissive action: Cortisol enhances effect of
other hormones, e.g., EPI stimulation of lipolysis
in adipose tissue.
Cortisol make vessels responsive : in the absence
of cortisol, BP decreases dramatically.
Cortisol increases RBCs, neutrophil and platelets.
Slide 20
Phamacological effects of cortisol
Cortisol has anti-inflammatory and
immunosuppressive effects at
pharmacological doses (much higher
conc. than physiological amounts).
So, glucocorticoid is used for
treatment of asthma, or for
suppressing the rejection response to
transplanted organs.
Slide 21
Control of Mineralocorticoids
Decreased blood pressure in kidney  renin
Liver
Angiotensinogen
Kidney Renin proteolysis
(granular
Angiotensin I
cell)
10 a.a.
8 a.a.
Angiotensin II
Lung
Angiotensinconverting
enzyme
Angiotensin II
stimulates
aldosterone
release.
Zona
glomerulosa
cells
Aldosterone
fig 14-10, pg 442
Slide 22
Control of Mineralocorticoids
Elevated extracellular K+ directly
stimulates glomerulosa cells to release
aldosterone.
 Aldosterone promotes K+ secrestion
by the kidney and therefore lower the
plasma K+ concentration.
Slide 23
Effects of Mineralocorticoids
Aldosterone stimulates Na+ (and hence
water) retention by kidney and K+ loss.
to increase in extracellular fluid volume
Increase blood pressure
Slide 24
Excess secretion of glucocorticoid
(Cushing’s syndrome)
thinner skin & red cheeks; lost connective tissue
(protein loss) of the skin.
Thin arms
& legs
; loss of
muscle
mass by
protein
catabolism
and fat
redistributi
on
Redistribution
of fat:
Round face
•hypertension
•Diabetes
•High susceptibility to
infection
•Impaired bone
metabolism (bone fx,
osteoporosis)
Slide 25
Deficiency in steroid production in
adrenal cortex (adrenal insufficiency)
Primary adrenal insufficiency (Addison’s disease)
has low cortisol and aldosterone;
Secondary adrenal insufficiency (low ACTH) just
lowers cortisol.
Addison symptom:
Electrolyte imbalance
Hypotension (Na reduction and decreased vascular reactivity),
Fatigue (Electrolyte imbalance),
Hypoglycemia
Skin pigmentation (high ACTH)
Slide 26
Adrenal Medulla
Is part of sympathetic nervous system, and is
called sympathoadrenal
Brain
system
Postganglionic
sympathetic
neuron
Spinal cord
Sympathetic
ganglia
Pass
without
synapsing
in chain
NE
Preganglionic
Sympathetic neurons
Adrenal
glands
Medulla
Blood
Epinephrine
Heart
Various
effector
organs
Adrenal
chromaffin
cells are
analogous to
sympathetic
postganglionic
neurons.
fig 14-12, pg 445
Slide 27
Adrenal chromaffin cells functions as
neuroendocrine cells.
They influence the activity of a variety of
effector organs throughout the body.
Slide 28
Sympathetic n.
Tyrosine
+
Tyrosine
hydroxylase
DOPA
Rate-limiting
Dopamine
Cortisol from
adrenal cortex
Norepinephrine
Chromaffin cells secrete
epinephrine into the
blood, instead of NE at a
synapse.
Input of sympathetic
stimulation increases epi
synthesis by increasing
activity of tyrosine
hydroxylase.
+
PNMT
Epinephrine
fig 14-13, pg 446
Slide 29
Epinephrine is
packaged within
chromaffin cells
into vesicles
known as
chromaffin
granules.
Slide 30
EPI released into blood has same effects
as sympathetic stimulation, but effects
last longer.
EPI increases heart rate and air flow, and
shunts blood from skin and viscera to
muscles.
“Fight or Flight”
bettering the chances of survival
Slide 31
EPI raises glycogenolysis in liver/muscle and
lipolysis in adipose; elevates blood glucose.
Liver
Glycogenolysis
Glucose
Lactate
Glycerol
Lactate
Glycogenolysis
Blood
Glucose
Fatty acids
Lipolysis
Adipose
tissue
Muscle
Heart & skeletal m.
fig 14-14,
pg 448
Slide 32