78 - Adrenocortical Hormones

78 - Adrenocortical Hormones
1. Each adrenal gland weighs about 4gms

2. Adrenal gland:
1. Cortex:
1. Zona glomerulosa - aldosterone - 15% of the cortex
2. Zona fasiculata - cortisol - 75% of the cortex
3. Zona reticularis - androgens
2. Medulla - Catecholamines
3. Zona glomerulosa contains aldosterone synthase - which helps in the synthesis of
mineralocorticoid aldosterone
4. The hormones secreted by adrenal cortex is strongly influenced by the presence of ACTH
secreted by the anterior pituitary gland
5. Aldosterone secretion is also mainly controlled by angiotensin II and potassium levels in the
ECF
6. Adrenocortical hormones are steroids derived from cholesterol (Figure 78-2)
7. Most of the cholesterol used for steroid synthesis is provided by LDL
8. Examples of few synthetic glucocorticoids which are more potent than cortisol:
1. Prednisone (4x)
2. Methylprednisone (5x)
3. Dexamethasone (30x)
9. Cortisol is bound to a globulin called cortisol binding globulin or transcortin. T1/2 = 60 to 90
minutes
10. Adrenal steroids are degraded in the liver and are conjugated especially to glucuronic acid
1. Conjugates -> 25% feces as bile
2. Rest -> urine
3. Kidney disease and disease of the liver reduces the excretion of the inactive
conjugates
11. Normal concentrations:
1. Aldosterone - 6 nanograms/100ml
2. Cortisol - 12 micrograms/100ml
12. Mineralocorticoid deficiency:
1. NaCl wasting
2. Hyperkalemia
3. Diminished cardiac output -> shock like state -> death
13. Cotrisol can also bind with mineralocorticoid receptors
14. Renal epithelial cells -> enzyme -> 11 ß hydroxysteroid dehydrogenase type 2, prevents
cortisol from binding to mineralocorticoid receptor
15. 11ßHSD2 functions:
1. Convert cortisol to cortisone
2. Effects on Intracellular redox state
16. Apparent mineralocorticoid excess syndrome (AME) - genetic deficiency of 11ßHSD2 activity
(cortisol will have substantial mineralocorticoid effect); ingestion of licorice which contains
glycyrrhetinic acid may also cause AME because of its ability to block 11ßHSD2 activity
17. Aldosterone increases reabsorption of Na+ and secretion of K+ ions
18. Excess aldosterone increases ECF volume but not Na+ concentration
1. Na+ reabsorption increases water flow along with it
2. ECF volume increases almost as much as retained Na+ but without much change in
Na+ concentration
19. Excess aldosterone -> increase in ECF -> continues for 1-2 days -> increases arterial
pressure -> pressure natriuresis & pressure diuresis -> aldosterone escape
20. Excess aldosterone -> hypokalemia -> muscle weakness
21. Aldosterone deficiency -> hyperkalemia -> cardiac toxicity - cardiac arrhythmias
22. Excess aldosterone increases tubular hydrogen ion secretion and causes alkalosis
(Intercalated cells)
23. Aldosterone increases NaCl reabsorption in sweat and salivary glands; to conserve body salt
in hot environments
24. Figure 78-4 (Aldosterone signalling pathway)
25. Non genomic effects of aldosterone:
1. Increased formation of cAMP
2. Stimulation of Phosphatidylinositol second messenger system
26. Regulation of aldosterone secretion:
1. Increased K+ concentration - most potent factor
2. Increased AT II - most potent factor
3. Decreased Na+ concentration
4. Increased ANP - atrial natriuretic peptide
5. ACTH from anterior pituitary
27. Cortisol is also known as hydrocortisone
28. Functions of glucocorticoids:
1. Carbohydrate metabolism:
1. Gene expression -> mRNAs -> enzymes required for gluconeogenesis
2. Mobilisation of amino acids from extrahepatic tissues, mainly from muscles
3. Antagonises insulins effect to inhibit gluconeogenesis in the liver
4. Decreased glucose utilization by cells -> insulin resistance by decreasing the
translocation of GLUT 4 to the cell membrane ‘
5. Adrenal diabetes - increase in blood glucose due to cortisol, even insulin
treatment wont decrease the blood sugar significantly, because cells become
.
resistant to insulin
. Protein metabolism:
. Decreased protein synthesis
. Increased protein catabolism
. Decrease in protein stores
. Weakness of muscles
. Increases liver and plasma proteins
. Increase in blood amino acid
. Diminished transport of amino acids into extrahepatic tissues
. Enhanced transport of amino acids into hepatic cells
. Fat metabolism:
. Mobilisation of fatty acids
. Increase fatty acid concentration in plasma
. Excess cortisol -> obesity
. Cortisol is important in resisting stress and inflammation:
. Trauma
. Infection
. Intense heat or cold
. Injection of norepinephrine
. Surgery
. Injection of necrotising substances beneath the skin
. Debilitating disease
. Restraining an animal
. How does cortisol have anti-inflammatory effects:
. Cortisol stabilises lysosomal membranes
. Cortisol decreases permeability of capillaries
. Cortisol decreases migration of white blood cells into the inflamed area and
phagocytosis of damaged cells
. Suppresses the immune system by decreasing lymphocyte reproduction
. Cortisol attenuates fever mainly because it reduced release of IL-1 from WBCs
. Cortisol also blocks the inflammatory response to allergic reactions
. Important diagnostic criterion for overproduction of cortisol by the adrenal gland:
. Lymphocytopenia
. Eosinopenia
. Cortisol administration also atrophies lymphoid tissues
. Cortisol control system (Figure 78-8)
. Cortisone to cortisol (11ßHSD1 - liver, skin, brain, Adipose, placenta); cortisol to cortisone
(11ßHSD2)
. Precursor of ACTH = POMC - pro-opiomelanocortin
. ACTH because it contains an MSH sequence, has about 1/30 as much melanocyte stimulating
effect
. Hypoadrenalsim - adrenal insufficiency - Addison’s disease
. Hyperadrenalism: Cushing’s syndrome
. Primary - adrenal tumor - Cushing’s syndrome
. Secondary - pituitary tumor - Cushing’s disease
. Men -> erectile dysfunction
. Women -> amenorrhea
. Moon face; buffalo like torso, acne and hirsutism
. Primary aldosteronism: Conn’s syndrome
. Tumor of zona glomerulosa cells
. Secretion of large amounts of aldosterone
. Hypokalemia -> muscle paralysis
. Adrenogenital syndrome:
. Excess androgens
. Female -> virile characters, beard, deeper voice, baldness, masculine distribution of
hair, growth of clitoris (resembles a penis), deposition of proteins in skin and muscles
. Male -> rapid development of male sexual organs
. Diagnosis - 17-ketosteroids in urine will be 10, 15 times greater than normal

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1. Each adrenal gland weighs about 4gms

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