Synthesis of cortisol

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Synthesis of cortisol
Stress
CRF corticotropic releasing hormone
Hypothalamus
cortisol
CRF
Pituitary
cortisol
Adrenocorticotropic hormone
ACTH
cortisol
Adrenal
Overproduction of ACTH skin darkening
Addisons disease
Hypofunctioning of adrenal cortisol
ACTH
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High levels of ACTH (MSH activity ?pigmentation)
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CORTISOL SYNTHESIS
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SYNTHESIS OF ALDOSTERONE
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SYNTHESIS OF TESTOSTERONE AND ESTRADIOL
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Synthesis of steroids 17 hydroxylase 11
hydroxylase 21 hydroxylase 18 hydroxylase
Cortisol 21 hydroxylase 17
hydroxylase 11 hydroxylase
Aldosterone 21 hydroxylase 18
hydroxylase 11 hydroxylase
Estradiol 17 hydroxylase Testosterone
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Mechanism of action of steroids
Transport
By being bound to plasma proteins
Sex hormone-binding globulin (SHBG) binds
and transports testosterone and estradiol
Corticosteroid Binding Globulin (CBG) binds
and transports cortisol
Specificity
Steroids act in only specific tissues and have
specific functions due to the presence of an
intracellular receptor specific for the hormone.
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Steroid Hormone Receptor
DNA binding domain
hormone binding domain
DNA binding domain
Zinc fingers bind to DNA
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• Coactivators-
• histone acetyltransferase activity
• affect RNA Polymerase II

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• Patients whose breast tumors are ER
• respond to hormone ablative therapy
• Anti estrogens (such as taxmoxifen)
• 2) Aromatase inhibitors (letrozole)
• (aromatase enzyme responsible for estradiol
  synthesis)

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• Peptides
• proteins (10-40,000 mw)
• membrane receptors
• act within minutes
• activate enzymes

• Steroids
• derived from cholesterol (300 mw)
• cytoplasmic and nuclear receptors
• act within hours
• affect transcription !!!!