2. Corticosterone about 4% , less potent .
3. Cortisone almost as potent as cortisol
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4. Prednisone (synthetic, 4 times as potent as
cortisol)
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5. Methylprednisone (synthetic, 5 times as potentas cortisol)
6. Dexamethasone (synthetic, 30 times as potent
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as cortisol)
Cholesterol
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ACTH Cholesterol desmolasePregnenolone
17 -hydroxylase
17-hydroxypregnenolone
3 HSD
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17-hydroxyprogesterone21-hydroxylase
11-deoxycortisol
11 -hydroxylase
cortisol
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Transport of Glucocorticoids
? Cortisol is bound in the circulation to an
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globulin called transcortin/CBG, minor degreeto albumin.
? Half life is 30-60 min that of corticosterone is
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50min
? Bound steroids are physiologically inactive.
? CBG is synthesized in liver ,production ed by
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estrogen ,&es in cirrhosis and nephrosis .
Interrelationship of free & bound form
? Why pregnant women have high plasma
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cortisol level without symptoms ofglucocorticoid excess?
? Why some patients of nephrosis have low
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total plasma cortisol without symptoms of
glucocorticoid deficiency ?
Metabolism & Excretion of
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Glucocorticoids
? Principal site of glucocorticoid catabolism is
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liver.? They are conjugated to glucuronic acid and
lesser extent to sulfates.
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? About 25% of these conjugates are excreted in
the bile and then in the feces and remaining
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excreted in the urine.Degradation of cortisol
Cortisol
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DihydrocortisolTetrahydrocortisol
Tetrahydrocortisol glucuronide
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Excretion in urine
Mechanism of cortisol action
? Glucocorticoids bind with receptor to form
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hormone receptor complex which activate
DNA to form mRNA.
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? mRNA causes synthesis of proteins which altercell function.
Physiological effects of Glucocorticoids
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? 95% of glucocorticoid activity of the
adrenocortical secretion results from
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secretion of cortisol/hydrocortisone.Effects of Cortisol on Carbohydrate
Metabolism
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Stimulation of Gluconeognesis? es enzymes for gluconeogenesis .
? Mobilisation of amino acids from extrahepatic tissue.
? ed hepatic giycogenesis.
? ed glucose utilization by cells.
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? in blood glucose level.WHAT IS ADRENAL DIABETES ?
Effects Of Cortisol On Protein & Fat
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Metabolism?Reduction in Cellular Protein.
?es Liver and Plasma proteins.
?es blood amino acid levels by mobilising
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amino acid from non-hepatic tissue.
1.Mobilisation of fatty acids.
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2.Typical obesity of excesscortisol
Effect of cortisol on fat metabolism
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? Mobilisation of fatty acid : from adipose tissue? es the conc. of frs in starvation ee fatty
acidsin the plasma
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? Enhances the oxidation fatty acids in cell.
?Above two mechanism utilizes fatty acid
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during starvation or other stressesOn Food Intake and Fat Distribution
? Cortisol es appetite by stimulating
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neuropeptide Y secretion from hypothalamus.? It stimulates lipogenesis by activating
lipoprotein lipase and G-6-PD activity of
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adipocytes in some parts of body.
? So cortisol excess leads to maldistribution pf
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fat.? Cortisol also es leptin synthesis.
?Why cortisol excess leads to truncal obesity,
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moon face &buffalo humpEffects on musculoskeletal system
? Cortisol increases performance of cardiac &
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skeletal muscle.? The inotropic effect is due to synthesis of Ach
at neuromuscular junction .
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? However, excess cortisol promotes proteolysis
, therefore it decreases muscle mass &
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strength.Anti-Inflammatory & Anti- Allergic
Effects(On pharmacological dose)
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Blocks early stages of Inflammation BY:? Stabilising Lysosomal Membrane.
?es Permeability of Capillaries.
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?es Migration of wbc into inflammed site.
?Suppress immune system :T cells
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?Attenuates fever by ing IL-1.Suppress Allergic Manifestations By ing Release of
Histamine by Mast cells & Basophils.
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? What is the role of cortisol in shock and anaphylaxis ??Why cortisol should be given with antibiotics ?
Effects on blood cells & lymphatic
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organs? Glucocorticoid es the no. of circulating
eosinophils by increasing their sequestration
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in the spleen and lungs
? Also lowers no. of basophils.
? es no. of neutrophils,platlets and rbcs.
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? es circulating lymphocyte by inhibiting theirmitotic activity and size of lymph node.
? es secretion of cytokines like IL-2.
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On bone
? Glucocorticoid stimulate bone resorbtion (by
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stimulating osteoclasts) .? Inhibits bone formation by ing collagen
synthesis and inhibits conversion of
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osteoprogenitor cells to osteoblast.
? It es absorbtion of calcium & es synthesis of
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active vit.D? So prolonged use of glucocorticoids will lead to
osteoporosis
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Effect on nervous system? Glucocorticoids are essential for normal
functioning of nervous system.
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? Insufficiency will lead to personality changes
like irritability, and lack of concentration.
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? Sensitivity to olfaction and taste stimuliincreases in adrenal insufficiency.
Effect on Kidney & Water metabolism
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? Cortisol es GFR so essential for rapidclearance of water load.
? It achieves this partly by inhibiting ADH
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secretion.
?Why water intoxication occur when glucose
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solution is infused in cortisol defcit patients ??What is glucose fever ?
On Vascular Response
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? Presence of glucocorticoids is essential forconstrictor action of adrenaline and nor
adrenaline.
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? So vascular collapse occurs in adrenal
insufficiency.
Other Effects
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? Large dose of glucocorticoids inhibits growth
es GH secretion, es TSH secretion.
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? During fetal life glucocorticoids accleratesmaturation of surfactant in the lungs.
Permissive Action
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Requirement of Glucocorticoids For ActionOf Other Hormones e.g
?Catecholamines :Lipolytic Effect
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Pressure Response
Bronchodilatation
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?Glucagon & Thyroid hormone-Calorigeniceffect
Resistance to stress
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? The most important function of of cortisol is toprotect the body against stress.
? Stress is defined as any change in the
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environment that changes an existing optimal
steady state.
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? Stress activates processes at the molecular,cellular or systemic level that tends to
maintain homeostasis.
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StressHypothalamus ,CRH
Anterior pituitary, ACTH
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Adrenal cortex, , cortisol
FFA release Vascular reactivity
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Calorie supply Maintenence of BP & blood vol.Regulation Of Cortisol Secretion
? ACTH stimulates cortisol secretion by ing
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cAMP? ACTH not only produces prompt increase in
glucocorticoids but also es the sensitivity of
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adrenal to subsequent dose of ACTH.
Regulation Of Cortisol by ACTH
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Hormone From Pituitary Gland? ACTH stimulates cortisol secretion.
? ACTH activates Adrenocortical cells to produce
steroids by ing cAMP.
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? Inhibitory effect of cortisol on theHypothalamus and on the Anterior Pituitary to
es ACTH secretion.
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ACTH
? ACTH is a single chain polypeptide containing 39
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amino acids.? It origin from proopiomelanocortin ( POMC) in
the pitutary.
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? Both basal secretion of glucocorticoids and ed
secretion provoked by stress are dependent on
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ACTH.? ACTH is secreted in irregular bursts throughout
the day and plasma cortisol tends to rise and fall
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in response to these bursts.
? In humans ,the bursts are frequent in early
morning, & 75% between 4a.m and 10a.m.
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? Bursts are least frequent in evening.
? The diurnal ACTH rhythm is located in
suprachiasmatic nuclei of the hypothalamus.
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? Free glucocorticoids inhibits ACTH seretion.
? In chronic adrenal insufficiency the rate of ACTH
synthesis is markedly increased.
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? Hence steroid therapy should not be abruptly
stopped.
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