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Physiology 3120 Lecture Notes - Cholesteryl Ester, Corticotropin-Releasing Hormone, Acth Receptor

Course Code
Tom Stavraky

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Human Physiology
Friday, March 5, 2010
“Endocrine VII”
Adrenal Physiology
Functional anatomy
Located just on top of kidney
Outer layer = cortex; produces steroids
Divided into several layers
Glomerulosa aldosterone
Fasciculata cortisol
Reticularis androgens (fairly significant source of androgens)
Adrenal steroidogenesis
All steroids ultimately come from cholesterol
Enzymes are cytochrome p450s (CYPs); found in membranes of mitochondria
and ER; energy comes from electron transport
Source of precursor cholesterol is LDL; cells have transporter for it, which moves
it into the cell; inside the cell, broken up into cholesterol esters
Cells have ACTH receptors (GPCRs), which increase cAMP and protein kinase
activity; increases activity of cholesterol ester hydrolase (CEH), which converts
cholesterol esters to naked cholesterol (rate-limiting step)
StAR (steroid acute regulatory protein) involved in moving into the mitochondria
(major rate-limiting step)
Some interconversions happen in (I) mitochondria, and others in (II) smooth ER
Movement of cortisol/aldosterone/androgens is by concentration gradients; which
one produced depends on which CYP protein is expressed
ACTH receptor mostly in fasciculate and reticularis
Regulated by pituitary ACTH
Cortisol transport and metabolism
75% in plasma bound to CBG (corticosteroid binding globulin, or transcortin);
primarily produced in liver
15% bound to HSA; “garbage-truck” of circulatory system
10% free; available to cross plasma membrane and have biological activity
Metabolized in liver; conjugated to glucoronic acid or sulphates, and excreted by
kidney, which is the basis for steroid urine tests
Inner layer = medulla; produces catecholamines
Composed of “chromaffin” cells
Secretion controlled by direct innervation
HPA axis
Hypothalamus (produces CRH [corticotropin releasing hormone])
Pituitary (produces ACTH [adrenocorticotropic hormone])
Adrenal (produces cortisol)
Responds to stress
Effects of cortisol
Increases blood glucose and amino acid levels in response to stress (need more glucose)
Increases muscle catabolism
Amino acid uptake in liver increases gluconeogenesis
Decreases glucose uptake by fat and muscle by inhibiting GLUT4 activity
Increases catabolism
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