Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest Glucocorticoids Lecture PPT
Glucocorticoids
1. Cortisol accounts for 95% of all glucocorticoid
activity, very potent.
2. Corticosterone about 4% , less potent .
3. Cortisone almost as potent as cortisol
4. Prednisone (synthetic, 4 times as potent as
cortisol)
5. Methylprednisone (synthetic, 5 times as potent
as cortisol)
6. Dexamethasone (synthetic, 30 times as potent
as cortisol)
Cholesterol
ACTH Cholesterol desmolase
Pregnenolone
17 -hydroxylase
17-hydroxypregnenolone
3 HSD
17-hydroxyprogesterone
21-hydroxylase
11-deoxycortisol
11 -hydroxylase
cortisol
Transport of Glucocorticoids
? Cortisol is bound in the circulation to an
globulin called transcortin/CBG, minor degree
to albumin.
? Half life is 30-60 min that of corticosterone is
50min
? Bound steroids are physiologically inactive.
? CBG is synthesized in liver ,production ed by
estrogen ,&es in cirrhosis and nephrosis .
Interrelationship of free & bound form
? Why pregnant women have high plasma
cortisol level without symptoms of
glucocorticoid excess?
? Why some patients of nephrosis have low
total plasma cortisol without symptoms of
glucocorticoid deficiency ?
Metabolism & Excretion of
Glucocorticoids
? Principal site of glucocorticoid catabolism is
liver.
? They are conjugated to glucuronic acid and
lesser extent to sulfates.
? About 25% of these conjugates are excreted in
the bile and then in the feces and remaining
excreted in the urine.
Degradation of cortisol
Cortisol
Dihydrocortisol
Tetrahydrocortisol
Tetrahydrocortisol glucuronide
Excretion in urine
Mechanism of cortisol action
? Glucocorticoids bind with receptor to form
hormone receptor complex which activate
DNA to form mRNA.
? mRNA causes synthesis of proteins which alter
cell function.
Physiological effects of Glucocorticoids
? 95% of glucocorticoid activity of the
adrenocortical secretion results from
secretion of cortisol/hydrocortisone.
Effects of Cortisol on Carbohydrate
Metabolism
Stimulation of Gluconeognesis
? es enzymes for gluconeogenesis .
? Mobilisation of amino acids from extrahepatic tissue.
? ed hepatic giycogenesis.
? ed glucose utilization by cells.
? in blood glucose level.
WHAT IS ADRENAL DIABETES ?
Effects Of Cortisol On Protein & Fat
Metabolism
?Reduction in Cellular Protein.
?es Liver and Plasma proteins.
?es blood amino acid levels by mobilising
amino acid from non-hepatic tissue.
1.Mobilisation of fatty acids.
2.Typical obesity of excess
cortisol
Effect of cortisol on fat metabolism
? Mobilisation of fatty acid : from adipose tissue
? es the conc. of frs in starvation ee fatty
acidsin the plasma
? Enhances the oxidation fatty acids in cell.
?Above two mechanism utilizes fatty acid
during starvation or other stresses
On Food Intake and Fat Distribution
? Cortisol es appetite by stimulating
neuropeptide Y secretion from hypothalamus.
? It stimulates lipogenesis by activating
lipoprotein lipase and G-6-PD activity of
adipocytes in some parts of body.
? So cortisol excess leads to maldistribution pf
fat.
? Cortisol also es leptin synthesis.
?Why cortisol excess leads to truncal obesity,
moon face &buffalo hump
Effects on musculoskeletal system
? Cortisol increases performance of cardiac &
skeletal muscle.
? The inotropic effect is due to synthesis of Ach
at neuromuscular junction .
? However, excess cortisol promotes proteolysis
, therefore it decreases muscle mass &
strength.
Anti-Inflammatory & Anti- Allergic
Effects(On pharmacological dose)
Blocks early stages of Inflammation BY:
? Stabilising Lysosomal Membrane.
?es Permeability of Capillaries.
?es Migration of wbc into inflammed site.
?Suppress immune system :T cells
?Attenuates fever by ing IL-1.
Suppress Allergic Manifestations By ing Release of
Histamine by Mast cells & Basophils.
? What is the role of cortisol in shock and anaphylaxis ?
?Why cortisol should be given with antibiotics ?
Effects on blood cells & lymphatic
organs
? Glucocorticoid es the no. of circulating
eosinophils by increasing their sequestration
in the spleen and lungs
? Also lowers no. of basophils.
? es no. of neutrophils,platlets and rbcs.
? es circulating lymphocyte by inhibiting their
mitotic activity and size of lymph node.
? es secretion of cytokines like IL-2.
On bone
? Glucocorticoid stimulate bone resorbtion (by
stimulating osteoclasts) .
? Inhibits bone formation by ing collagen
synthesis and inhibits conversion of
osteoprogenitor cells to osteoblast.
? It es absorbtion of calcium & es synthesis of
active vit.D
? So prolonged use of glucocorticoids will lead to
osteoporosis
Effect on nervous system
? Glucocorticoids are essential for normal
functioning of nervous system.
? Insufficiency will lead to personality changes
like irritability, and lack of concentration.
? Sensitivity to olfaction and taste stimuli
increases in adrenal insufficiency.
Effect on Kidney & Water metabolism
? Cortisol es GFR so essential for rapid
clearance of water load.
? It achieves this partly by inhibiting ADH
secretion.
?Why water intoxication occur when glucose
solution is infused in cortisol defcit patients ?
?What is glucose fever ?
On Vascular Response
? Presence of glucocorticoids is essential for
constrictor action of adrenaline and nor
adrenaline.
? So vascular collapse occurs in adrenal
insufficiency.
Other Effects
? Large dose of glucocorticoids inhibits growth
es GH secretion, es TSH secretion.
? During fetal life glucocorticoids acclerates
maturation of surfactant in the lungs.
Permissive Action
Requirement of Glucocorticoids For Action
Of Other Hormones e.g
?Catecholamines :Lipolytic Effect
Pressure Response
Bronchodilatation
?Glucagon & Thyroid hormone-Calorigenic
effect
Resistance to stress
? The most important function of of cortisol is to
protect the body against stress.
? Stress is defined as any change in the
environment that changes an existing optimal
steady state.
? Stress activates processes at the molecular,
cellular or systemic level that tends to
maintain homeostasis.
Stress
Hypothalamus ,CRH
Anterior pituitary, ACTH
Adrenal cortex, , cortisol
FFA release Vascular reactivity
Calorie supply Maintenence of BP & blood vol.
Regulation Of Cortisol Secretion
? ACTH stimulates cortisol secretion by ing
cAMP
? ACTH not only produces prompt increase in
glucocorticoids but also es the sensitivity of
adrenal to subsequent dose of ACTH.
Regulation Of Cortisol by ACTH
Hormone From Pituitary Gland
? ACTH stimulates cortisol secretion.
? ACTH activates Adrenocortical cells to produce
steroids by ing cAMP.
? Inhibitory effect of cortisol on the
Hypothalamus and on the Anterior Pituitary to
es ACTH secretion.
ACTH
? ACTH is a single chain polypeptide containing 39
amino acids.
? It origin from proopiomelanocortin ( POMC) in
the pitutary.
? Both basal secretion of glucocorticoids and ed
secretion provoked by stress are dependent on
ACTH.
? ACTH is secreted in irregular bursts throughout
the day and plasma cortisol tends to rise and fall
in response to these bursts.
? In humans ,the bursts are frequent in early
morning, & 75% between 4a.m and 10a.m.
? Bursts are least frequent in evening.
? The diurnal ACTH rhythm is located in
suprachiasmatic nuclei of the hypothalamus.
? Free glucocorticoids inhibits ACTH seretion.
? In chronic adrenal insufficiency the rate of ACTH
synthesis is markedly increased.
? Hence steroid therapy should not be abruptly
stopped.
This post was last modified on 30 November 2021