Download adrenal cortex

ADRENAL CORTEX
Introduction
• Adrenal Location
– Superior Pole of
each Kidney
– Retroperitoneal
– Embedded in the
Perirenal fat pad.
– Left gland sits
slightly more
superior than right
gland
Adrenal Gland
• Adrenal Cortex
• Adrenal Medulla/
Chromaffin Tissue
• Different
embryological
origins
• Not together
below birds
Adrenal Cortex
• Embryology
– Intermediate
Mesoderm
• Zones
– Zona Glomerulosa
– Zona Fasciculata
– Zona Reticularis
Medulla
Adrenal Cortex Cytology
• Lipid Inclusions
• Well Developed SER
• Mitochondria with
Tubular Cristae
• Capillary Adjacent to
each Cell
Cholesterol
Side Chain
• LDL
• De Novo Synthesis
Mineralocorticoids
Side-Chain
Cleavage
3-OH
dehydrogenase
Steroid Pathways
GlucoAndrogens
corticoids
Estrogen
Aromatase
21-hydroxylase
11-hydroxylase
18-hydroxylase
18-OH
steroid
dehydrog.
17-OH Steroid
Dehydrogenase
17-OHase
C17-20 Lyase
16-OHase
Mineralocorticoids
Mineralocorticoids
Side-Chain
Cleavage
3-OH
dehydrogenase
Z. Glomerulosa
GlucoAndrogens
corticoids
Estrogen
Aromatase
21-hydroxylase
11-hydroxylase
18-hydroxylase
18-OH
steroid
dehydrog.
17-OH Steroid
Dehydrogenase
17-OHase
C17-20 Lyase
16-OHase
Mineralocorticoids
• C-21 Steroids
• Primarily produced by zona glomerulosa
• Principal mineralocorticoid is
aldosterone
• Aldosterone actions
– Promote Na+ reabsorption
– Inhibit K+ reabsorption
– Antidiuretic
– Acts primarily on the cortical collecting duct
& DCT
Regulation of
Aldosterone Secretion
Na+
K+
 Na+
 K+
Z. Glomerulosa
Aldosterone
Na+
Reabsorption
Kidney
K+ Reabsorption
Regulation of
Aldosterone Secretion
Angiotensinogen
Kidney
Juxtaglomerular Renin
Cells
Blood
Pressure
Angiotensin-I
Blood Volume
Water Reabsorption
Na+
Reabsorption
Kidney
Lung
Converting
Enzyme
Angiotensin-II
Aldosterone
Z. Glomerulosa
Regulation of
Aldosterone Secretion
Hypothalamus
CRH
Anterior Pituitary
ACTH
Z. Glomerulosa
Aldosterone
Atrial Natriuretic
Hormone
• 28 amino acid peptide
• Similar peptides produced in other organs
• Actions
– cGMP is second messenger
– Increases GFR
– Inhibits Na+ and water reabsorption
Regulation of ANH
Venous
Return
Venous
Return
Atrial Stretch
Receptors
ANH
 Blood
Volume
Kidney
Water
Reabsorption
Na+
Reabsorption
Glucocorticoids
Mineralocorticoids
Side-Chain
Cleavage
3-OH
dehydrogenase
Z. Fasiculata
GlucoAndrogens
corticoids
Estrogen
Aromatase
21-hydroxylase
11-hydroxylase
18-hydroxylase
18-OH
steroid
dehydrog.
17-OH Steroid
Dehydrogenase
17-OHase
C17-20 Lyase
16-OHase
Which ones are
glucocorticoids?
•
•
•
•
Cortisol
11-deoxycorticosterone
17-hydroxyprogesterone
17-hydroxypregnenolone
• Cortisol Most Potent
• 11-deoxycorticosterone, very weak, but does
act as feedback effector and has potent
mineralocorticoid activity.
• Remainder are inactive
Serum binding
proteins
• Corticosteroid binding globulin (CBG)
– 75% of Cortisol bound to CBG
– 10% of Aldosterone bound to CBG
• Albumin
– 15% of Cortisol bound to Albumin
– 50% of Aldosterone bound to Albumin
• Free
– 10 % of Cortisol
– 40 % of Aldosterone
Actions of the
Glucocorticoids
Anti-inflammatory
• Inhibit Prostaglandin production
– Inhibit phospholipase A2
• Inhibit secretion of Interleukin-I
• Prevents movement of PMNs,
lymphocytes, & monocytes from
blood into areas of injury.
• Decrease lymphocyte production
Intermediary
Metabolism
•
•
•
•
•
Stimulates gluconeogenesis
Protein catabolic
Decrease glucose catabolism
Increase lipolysis
Inhibit DNA synthesis.
Growth
• Glucocorticoids inhibit mitosis
• Inhibit bone formation and
mineralization
– Decrease intestinal absorption of Ca++
– Stimulates PTH (secondarily)
Connective Tissues
• Inhibit collagen formation
• Decreased bone deposition
Blood
• Increased intravascular levels of
neutrophils
• Decreased intravascular levels of
lymphocytes, monocytes, &
eosinophils
• Diminished immune response
Cardiovascular
• Increase blood pressure
– Increased cardiac output
– Increased vascular tone
– Possibly augmenting action of
catecholamines
– Increasing number of adrenergic
receptors
Effects on CNS
• Easily enter Brain
• Neurons have glucocorticoid
receptors
• Physiologic effect unknown
• Excess or deficiency of
glucocorticoids known to profoundly
alter behavior and cognitive function.
Effects on Other
Hormones
• Inhibit TSH production
• Inhibit GnRH production
Ulcer formation
• Inhibit Prostaglandin production
• Immunosuppression
ACTH
Side-Chain
Cleavage
3-OH
dehydrogenase
Mineralocorticoids
Z. Fasiculata
GlucoAndrogens
corticoids
Estrogen
Aromatase
21-hydroxylase
11-hydroxylase
18-hydroxylase
18-OH
steroid
dehydrog.
17-OH Steroid
Dehydrogenase
17-OHase
C17-20 Lyase
16-OHase
Regulation of
Glucocorticoid Secretion
STRESS
Circadian
Rhythm
Hypothalamus
CRH
Anterior Pituitary
ACTH
Z. Fasciculata &
Reticularis
Cortisol
General Adaptation
Syndrome (Selye)
Cortisol
 STRESS
• Alarm
• Resistance
• Exhaustion---Death
Time 
Adrenal Androgens
• Dehydroepiandrosterone (DHEA)
– DHEA-S
• Androstenedione
Fetal Adrenal Cortex
• Develops first in fetal adrenal gland
• Produces androgens (DHEA)
• Replaced by definitive cortex
Pathologies of the
Adrenal Cortex
Adrenocortical Insufficiency
(Addison’s Disease)
• Signs & symptoms
– Weakness, Fatigue
– Anorexia, Weight loss
– Hyperpigmentation (primary only)
– Hypotension
– G-I disturbances
– Salt craving
• Crisis
• Treatment
Hypersecretion
(Cushing’s Disease)
• Primary, secondary, or tertiary
• Ectopic ACTH production
• Signs and symptoms
– Obesity
– Thinning of the skin
– Striae
– Hirsutism
– Hypertension
Hypersecretion
(Cushing’s Disease)
– Weakness
– Gonadal dysfunction
– Glucose intolerance
• Treatment
Androgenital
syndrome
• Excess adrenal androgen
production.
• Maybe due to tumor
Enzyme Deficiencies
Side-Chain
Cleavage
3-OH
dehydrogenase
21-Hydroxylase Deficiency
21-hydroxylase
17-OHase
C17-20 Lyase
Enzyme Deficiencies
Side-Chain
Cleavage
3-OH
dehydrogenase
11-Hydroxylase Deficiency
21-hydroxylase
11-hydroxylase
17-OHase
C17-20 Lyase
Enzyme Deficiencies
Side-Chain
Cleavage
3-OH
dehydrogenase
3-Hydroxysteroid Dehydrogenase
Deficiency
17-OHase
C17-20 Lyase