Glucocorticoid Physiology

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Glucocorticoid Physiology

• Synthesis and Release from the Adrenal
• Circulation in the Blood
• Glucocorticoid Effects on the Body
• Target Tissues
• Physiological Actions of Glucocorticoids
• Liver
• Adipose Tissue
• Skeletal Muscle
• Pharmacological Uses of Glucocorticoids

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Diurnal Variation of Glucocorticoids
Change
Note Related to sleep-Wake Cycle
100
8-10 am
0
-100
2 am
12 Midn
12 Noon
12 Midn
Time
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Circulating Bound Cortisol
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F R E E C O R T I S O L
12
10
8
6
Binding Capacity
4
2
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
Ug/100ml
TOTAL PLASMA CORTISOL
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Target Tissues of Glucocorticoids

• Brain
• Liver
• Retina
• Testes
• Fibroblasts
• Kidneys
• Skeletal Muscle
• Skin

• Heart
• Lymphoids
• Smooth Muscle
• Lung
• Bone
• Stomach
• Intestines
• Adipose Tissue

Most Important
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General Cell
Cortisol
mRNA
Rough E.R.
Actions
PROTEIN (Enzyme)
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Liver Cell
Cortisol
N2 Balance
Protein
Gluconeogenesis
Protein Synthesis
A.A.
Glycogen
Gluc.
Glucose
Urea
A.A.
Glucose
Plasma
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Cortisol Effects on Glucose
Glycogen Phosphorylase a
G-P(b)
P K ATP
UDP-G
Glycogen
Glucose
G-6-PO4
G-1-PO4
G-6-PO4ase
Synthetase I
Pyrophosphorylase
Phosphoglucomutase
Synt. D phosphatase
Synthetase D
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Adipose Cell
Cortisol
-N2 Balance
Protein
Free Fatty Acids
Neutral Fat Breakdown
Glycerol
Gluc.
Blocks Transport
FFAs
Plasma
Glycerol
Glucose
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Muscle Cell
Cortisol
N2 Balance
Protein
Glucose
Glycogen
Protein Synthesis
A.A.
Protein Breakdown
A.A.
Plasma
Glucose
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Integration of Cortisol Effects
1. Adipose Tissue
Lipolysis, Glucose, F.F.A.s
Glyc.
Lipogenesis
2. Liver Tissue
Glycogen Synt., Gluconeogenesis,
GLUCOSE PLASMA
3. Muscle Tissue
Prot. Breakdown A.A.s, Glucose Use
Prot. Synthesis
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Pharmacological Effects of the Glucocorticoids

• Osteoporosis of Bone
• Skin Thinning and Wasting, reduced protein,
  increased Stria
• Connective Tissue Breakdown
• Blood Changes
• Neutrophils Thrombocytes RBCs
• Lymphocytes Eosinophils Basophils
• CNS Effects Mood Stability, Psychoses,
• Excitability
• H2O Retention

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Pharmacological Effects of the Glucocorticoids
Part 2

• Supressed Immune Response--Antiinflammatory
  Reaction
• Destruction of Eosinophils
• Stabilization of Lysosomal Membranes
• Inhibition of Arachidonic A. Metabolism
• Inhib. of Phospholipase A2
• Stim. lipocortin production
• Decreased Prostaglandins Prostacyclins
  Leucotrienes Vasoconstriction and loss of Edema

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Adrenal Mineralocorticoids

• Aldosterone Synthesis and Release controlled by
  Angiotensin II
• DOC has weak Aldo. activity
• partial maintenance of zone by ACTH
• Synthesis in zona glomerulosa of adrenal cortex
• not much hormone stored synthesis and release
  is story
• Normal plasma concentration is 0.015 mg/100ml
• 40 free, 60 bound to albumin
• Potency 3,000X that of cortisol, DOC

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Physiology of Aldosterone

• Synthesis and Release controlled by Na and K in
  plasma via Angiotensin II
• Primary stimuli are Na and K in plasma
• Primary Effects are to Na P KP
• (H2O follows Na )

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Aldosterone Physiology Part 2

• Secondary Effect is to metabolic buffers
• NH4 excretion
• Mechanisms of action proposed
• Na-K-ATPase stimulation
• Mitochondrial ATP synthesis stimulation
• Na-permease (luminal border) theory
• Target tissues Kidneys, sweat glands, salivary
  glands, GI, muscle, bone

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Aldosterone Physiology Part 3
Na and K in plasma and directly at z. glom.
Renin (Kidneys)
Na and K in plasma
Angiotensin I Angiotensinogen
(from Liver)
Converting Enzyme (Lungs)
Aldosterone
Adrenals (z.glom.)
Angiotensin II
Cholesterol
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