Download MBBS Glucocorticoids Lecture PPT

Glucocorticoids

1. Cortisol accounts for 95% of all glucocorticoid

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activity, very potent.

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 potent

as cortisol)

6. Dexamethasone (synthetic, 30 times as potent

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as cortisol)

Cholesterol

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ACTH Cholesterol desmolase
Pregnenolone
17 -hydroxylase
17-hydroxypregnenolone
3 HSD

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17-hydroxyprogesterone
21-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 degree

to 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 of

glucocorticoid 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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Dihydrocortisol

Tetrahydrocortisol

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 alter

cell 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 excess

cortisol
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 stresses
On 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 hump
Effects 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 their

mitotic 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 stimuli

increases in adrenal insufficiency.
Effect on Kidney & Water metabolism

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? Cortisol es GFR so essential for rapid

clearance 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 for

constrictor 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 acclerates

maturation of surfactant in the lungs.
Permissive Action

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Requirement of Glucocorticoids For Action

Of Other Hormones e.g

?Catecholamines :Lipolytic Effect

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Pressure Response

Bronchodilatation

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?Glucagon & Thyroid hormone-Calorigenic

effect
Resistance to stress

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? The most important function of of cortisol is to

protect 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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Stress

Hypothalamus ,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 the

Hypothalamus 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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