Adrenocorticoids

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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
Aldosterone (11b,21-dihydroxy- pregn-4-ene-3,18,20
-trione)
Hydrocortisone (11b,17a,21-trihydroxy- pregn-4-ene
-3,20-dione)
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Overall Equilibrium in Aldosterone
Opened form hemi-acetal
form
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 in-sufficiency (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
? 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 Action
Mineralocorticoid Action
Receptor Receptor
Lipocortin Aldosterone-
induced protein
Regulates Na-K-ATPase Pump
Na Influx
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Biosynthesis of Adrenocorticoids
Corticosterone
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Metabolism of Adrenocorticoids
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Structure-Activity Relationships
Anti- Salt-
Plasma inflammatory retaining
half activity activity life

Hydrocortisone 1 1
120 m
Cortisone 0.8
0.8 30 m
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Structure-Activity Relationships
Anti- Salt-
Plasma inflammatory retaining
half activity activity
life
Prednisone 4
1 60 m
Prednisolone 4 0.6
115-212 m
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Structure-Activity Relationships
Anti- Salt-
Plasma inflammatory retaining
half activity activity
life
6a-methyl 4 0
78-188 m prednisolone
Triamcinolone 5
0 200 m
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Structure-Activity Relationships
Anti- Salt-
Plasma inflammatory retaining
half activity activity
life
Dexamethasone 30 0
110-210 m
Betamethasone 35 0
300 m
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Structure-Activity Relationships
Anti- Salt-
Plasma inflammatory retaining
half activity activity
life
Aldosterone 0.2 800
30 m
11-deoxy 0
40 60 m corticosterone
Fludrocortisone 10 800
300 m