Transcript Adrenocorticoids Steroidal hormones synthesized by the adrenal glands An inner medulla, which is a source of the catecholamines epinephrine and norepinephrine. An outer cortex, which secretes several classes.

Adrenocorticoids
Steroidal hormones
synthesized by the
adrenal glands
An inner medulla, which is a source of
the catecholamines epinephrine and
norepinephrine.
An outer cortex, which secretes several
classes of steroid hormones
(glucocorticoids and mineralocorticoids,
plus a few others).
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Adrenocorticoids
O
HO
C H3
OH
HO
OH
C H3
O
C HO
OH
C H3
O
O
Hydrocortisone
(11b,17a,21-trihydroxypregn-4-ene-3,20-dione)
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Aldosterone
(11b,21-dihydroxypregn-4-ene-3,18,20-trione)
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Overall Equilibrium in Aldosterone
Opened form
HO
O
CHO
hemi-acetal form
HO
OH
O
O
C H3
OH
C H3
O
O
Aldosterone
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Adrenocorticoids
 Biological Activities
1. Glucocorticoid Activity
1.1 Effects on Metabolism
1.1.1 Stimulation of gluconeogenesis, particularly in the liver
1.1.2 Mobilization of amino acids from extrahepatic tissues
1.1.3 Inhibition of glucose uptake in muscle and adipose tissue
1.1.4 Stimulation of fat breakdown in adipose tissue
1.2 Effects on Inflammation and Immune Function
1.2.1 Anti-inflammatory properties
1.2.2 Immunosuppressive properties
1.3 Other Effects of Glucocorticoids
1.3.1 Multiple effects on fetal development (promote maturation of the lung)
1.3.2 Miscellaneous effects (Excessive glucocorticoid levels affect many systems, e.g.,
inhibition of bone formation, suppression of calcium absorption and delayed wound
healing.)
2. Mineralocorticoid Activity
2.1 Effect on Electrolytes
2.1.1 Increased re-absorption of sodium
2.1.2 Increased renal excretion of potassium
2.2 Effect on Water
2.2.1 Increased re-absorption of water
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Adrenocorticoids
 Disease States

Addison's disease: Affects about 1 in 100,000 people; caused by adrenal insufficiency (90%); typical by auto-immune disorders; both cortisol and
aldostertone hormones are lacking.

Cushing's disease: Affects about 10 to 15 million people / yr; caused by
adrenal hyper-activity (cortisol); typical because of tumor growth exposure to
prednisone for asthma, rheumatoid arthritis, lupus or other inflammatory diseases

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Conn's syndrome: May affect 15% of patients with high blood pressure;
caused by hyper production of aldosterone; inability of adrenal cortex to carry
out 17a-hydroxylation; hypertension, loss of potassium in the urine, muscle
weakness and passing of large volumes of urine (polyuria)
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Glucocorticoids
 Selected Indications
•
Allergic Rhinitis
Rheumatoid Arthritis
•
Asthma
Multiple Sclerosis
•
Carpal Tunnel Syndrome
Dermatitis
•
COPD
Osteoarthritis
•
Cystic Fibrosis
Temporal Arteritis
•
Gout
Psoriasis
•
Herniated Disc
Shingles
•
Inflammatory Bowel Disease
Tennis Elbow
•
Sinusitis
Lupus Erythematosus
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Biochemical Mechanism of Action
Cortisol Aldosterone
Anti-inflammatory
Mineralocorticoid
Action
Action
Receptor Receptor
Lipocortin
Aldosteroneinduced protein
Prostaglandins
leucotrienes
Cell membrane
phospholipids
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Regulates
Na+-K+-ATPase Pump
Na+ Influx
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Biosynthesis of Adrenocorticoids
OH
H 3C
H 3C
R
CH3
CH3
CH3
H 3C
O
CH3
CH3
HO
H 3C
CH3
O
HO
CH3
OH
HO
O
HO
OH
CH3
CH3
CH3
O
HO
OH
CH3
O
1 7 a -H y d ro x y p ro g e s te ro ne
2 1 -H y d ro x y p ro ge s te ro ne
P ro g e s te ro n e
OH
O
O
CH3
O
P re g n e n o lo n e
O
CH3
CH3
HO
C h o le s te ro l
R = -C H 2 C H 2 C H 2 C H (C H 3 ) 2
O
O
1 1 -D e o x y c o rtis o l
O
C H3
C H3
O
Corticosterone
H y d ro c o rtis o n e
OH
O
CHO
HO
CH3
O
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A ld o s te ro n e
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Metabolism of Adrenocorticoids
HO
R
CH3
OH
OH
CH3
O
O
HO
CH 3
OH
O
R
OH
O
CH3
OH
O
OH
CH3
CH 3
OH
OH
CH 3
O
O
CH 3
O
H y d ro c o rtis o n e
C o rtis o n e
O
R
CH3
OH
OH
CH3
N o te : R = -H o r -O H
HO
H
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Structure-Activity Relationships
Antiinflammatory
activity
O
HO
C H3
OH
OH
C H3
Hydrocortisone
Saltretaining
activity
Plasma
half
life
1
1
120 m
0.8
0.8
30 m
O
O
O
C H3
OH
OH
C H3
Cortisone
O
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Structure-Activity Relationships
O
O
C H3
Antiinflammatory
activity
OH
Saltretaining
activity
Plasma
half
life
OH
C H3
Prednisone
O
HO
O
C H3
4
1
4
0.6
60 m
OH
OH
C H3
O
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Prednisolone
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115-212 m
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Structure-Activity Relationships
Antiinflammatory
activity
O
C H3
HO
OH
Saltretaining
activity
Plasma
half
life
OH
C H3
6a-methyl
prednisolone
O
4
0
78-188 m
C H3
O
HO
C H3
C H3
OH
O
O
Triamcinolone
O
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0
200+ m
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Structure-Activity Relationships
O
C H3
HO
C H3
F
OH
Antiinflammatory
activity
Saltretaining
activity
Plasma
half
life
OH
C H3
Dexamethasone
30
0
110-210 m
O
O
C H3
HO
C H3
F
OH
OH
C H3
Betamethasone
35
0
300+ m
O
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Structure-Activity Relationships
O
C HO
HO
Antiinflammatory
activity
OH
Saltretaining
activity
Plasma
half
life
0.2
800
30 m
0
40
60 m
C H3
Aldosterone
O
O
C H3
OH
C H3
11-deoxy
corticosterone
O
O
C H3
HO
C H3
F
OH
OH
Fludrocortisone
10
800
300+ m
O
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