BIOLOGY OF ADRENAL GLAND

ANATOMY OF ADRENAL GLAND

• Lie in the
retroperitoneum
above or medial
to the upper poles
of the kidney
• Surounded by the
fibrous capsule
• Cortex comprises
90% of the
adrenal weight
• Inner medula is
about 10%
 FUNCTIONAL
ANATOMY AND
ZONATION
HORMONES OF THE ADRENAL CORTEX

Zona • Contains abundant smooth endoplasmic

reticulum
Glomerulosa • Produce mineralocorticoid aldosterone

Zona • Contains abundant lipid droplets

• Produce glucocorticoids, cortisol, and
fasciculata androgens

Zona • Produce glucocorticoids and androgen

Reticularis
ADRENAL STEROID HORMONE
SYNTHETIC PATHWAY
 KEY ENZYMES INVOLVED IN STEROIDOGENESIS
ENZYME AND RELEVANCE PHYSIOLOGIC FUNCTION CONSEQUENCE OF
DEFICIENCY
21β-Hydroxylase Converts progesterone to Decreased cortisol and
Accounts for 95% of 11-deoxycorticosterone aldosterone; Loss of
genetic abnormalities in and 17α - sodium because of
adrenal steroid hormone hydroxyprogesterone to mineralocorticoid
synthesis 11-deoxycortisol deficiency; Virilization
because of excess
androgen production
11β-Hydroxylase converts 11- Excess 11-deoxycortisol
Second most frequent deoxycorticosterone to and 11-
abnormality in adrenal corticosterone; 11- deoxycorticosterone;
steroid hormone synthesis deoxycortisol to cortisol Excess mineralocorticoid
activity; Salt and water
retention
11β-Hydroxysteroid Metabolizes the active Decrease in glucocorticoid
dehydrogenase type 2 forms of glucocorticoids inactivation in
Inhibited by glycyrrhetenic into inactive from that mineralocorticoid-sesitive
acid, a compund of licorice have less affinity for cells; excess
mineralocorticoid receptor mineralocorticoid activity.
• Glucocorticoids (cortisol) are secreted in high
amounts = 10-20 mg/day, from zona fasciculata
under the control of ACTH
• Mineralocorticoids (aldosterone) are secreted in
low amount = 100-150 μg/day, from zona
glomerulosa under the control of angiotensin II
• Adrenal androgen (DHEA, DHEAS,
ndrostenedione) are secreted about >20mg/day,
secretion is fascilitated through the expression of
stereidogenic enzymes in a specific zonal manner.
 GLUCOCORTICOID
Secretion
• Release occurs within 15 min of the surge in ACTH (7-15x/d)
• Its secretion is sensitive to light, sleep, stress, and disease
Metabolism
• Half life = 70-90 min
• cortisol is bounding to transcortin, with normal levels of transcortin = 3-4
mg/dL, saturated with cortisol levels of 28μg/dL
• Hepatic shynthesis of transcortin is stimulated by estrogen and
decreased by hepatic disease.
• Metabolism occur in liver and kidney
• inactive hormones are eleminated as urinary metabolites.
REGULATION OF CORTISOL SECRETION
 PHYSIOLOGIC EFFECTS OF GLUCOCORTICOIDS
SYSTEM EFFECT
Metabolism Degrades muscle protein and increase nitrogen axcretion;
increases gluconeogenesis and plasma glucose levels; increases
hepatic glycogen synthesis; decrease glucose and amino acid
utilization; increases fat mobilization; redistributes fat; permissive
effect of glucagon and catecholamine effects.

Hemodynamic Maintain vascular integrity and reactivity; maintains

responsiveness to catecholamine pressor effects; maintain fuid
volume; promoting renal water excretion.

Immune function Increases anti-inflammatory cytokine production; decrease

proinflammatory cytokine production; decreases inflammation by
inhibiting prostaglandin and leukotriene production; inhibits
bradykinin and serotonin inflammatory effects; decreases
circulating eosinophil, basophil, and lymphocyte count; impairs
cell mediated immunity; increases neutrophil, platelet, and red
blood cell counts.
Central Nervous Modulates perception and emotion; decreases CRH and ACTH
System release
 MINERALOCORTICOID
Secretion
• Regulated by angiotensin II and extracellular K and ACTH
• Stimulus for aldosterone release is a decrease intravascular blood volume
and elevations in circulation potassium concentration.

Metabolism
• Plasma aldosterone levels average 0.006-0.01 μg/dL (in contrast cortisol
level 13.5μg/dL )
• Plasma half life = 15-20 min
• Metabolized in liver to tetrahydroglucuronide (40%)
• Excreted in urine (1%)
• 5% of aldosterone is excreted in acid labile form
REGULATION OF ALDOSTERONE SECRETION
 MINERALOCORTICOID
Physiologic Function
• Regulate renal sodium reabsorption
• Increased renal sodium reabsoption in salivary and sweat gland
• Increased kalium excretion from the colon
• Positive inotropic effect on the heart
• Myocardial fibrosis in ventricular hypertrophy
• In the brain, aldosterone affects neural regulation of blood
pressure, salt appetite, volume regulation, and sympathetic
outflow.
 ADRENAL ANDROGEN
Secretion
• DHEA secreted about 4 mg/d, DHEAS 7-15 mg/d, androstenedione 1.5 mg/d,
testosterone 0.05 mg/d.
• DHEA is a crucial precursor of human sex steroid biosynthesis and exerts
androgenic or estrogenic activity
• DHEAS stimulates androgen secretion
• DHEA and androstenedione demonstrate a circardian rhythm.
Metabolism
• Adrenal androgens are converted into andorstenedionepotent androgens
or estrogens in the pheripheral tissues
• DHEA nad DHEAS increases in children (6-8 yo); peak at ages of 20-30 yo;
continue to decrease with age.
 ADRENAL ANDROGEN

• Excessive adrenal androgen  premature

MALE penile enlargement and early development of
secondary sexual characteristics (in boys)

• In follicular phase: as precursor for 2/3 of

testosterone production and ½ of
FEMALE dihydrotestosterone production
• Midcycle: as precursor for 40% of testosterone
production.
 ADRENAL ANDROGENS

Physiologic Function
• Low levels of DHEA are associated with
cardiovascular disease in men and
increased risk of premenopausal breast
and ovarian cancer in women.
• High levels of DHEA increase the risk of
postmenopausal breast cancer
ADRENAL MEDULLA
 ANATOMY
• The adrenal medulla occupies a central
position in the widest part of the gland, with
only small portions extending to the narrower
part
• The mass adrenal gland in adult : 1000mg
(15% of total both adrenal gland)
• Medulla = sympathetic nervous system
ganglion
Microscopic structure
• Consist of chromaffin cells or pheochromocytes (Large ovoid
columnar cells )
• Catecholamines (epinephrine and norepinephrine)
comprises about 20% of the neurosecretory vesicles

Nerve and Blood Supply

• Inervated by preganglionic fibers of the sympathetic nervous
system
• Perfused by the superior, middle, and inferior adrenal
branches of the inferior phrenic artery, directly from aorta
and renal arteries.
 HORMONES OF ADRENAL MEDULLA

• Catecholamine epinephrine
Main • Catecholamine norepinephrine
Products

• chromogranins
• ATP
Additional • Endogenous opioid peptide
Products • Adrenomedullin
 CATECHOLAMINES
Release
• Direct response to sympatethic nerve stimulation

Transport and Metabolism

• Half life : 10 sec – 1.7 min
• Catecholamine are degraded by catechol-O-
methyltrasnferase (COMT) or monoaminooxidase in the
liver
• Monoamino oxidase + COMT +epi/norepinephrine 
vanyllilmandelic acid then excreted in the urine
TARGET ORGAN CELLULAR EFFECTS OF
CATECHOLAMINE
α Adrenergic mediated Β Adrenergic mediated
vasoconstriction Vasodilatation
Iris dilataton Cardioacceleration
Cardiac contractility Increased myocardial strength
Intestinal sphincter contraction Intestinal and bladder wall relaxation
Bladder sphincter contraction Uterus relaxation
Bronchoconstriction Bronchodilatation
Pilomotor contraction Calirogenesis
Uterine smooth muscle contraction Glycogenolisis
Intestinal relaxation Lipolysis
Hepatic glucose production