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Adrenal physiology

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Physiology 3120
Tom Stavraky

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  Components  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 • Lipid hydrolysis  increased circulating fatty acids • Bone and connective tissue catabolism  osteopenia, thinning of skin and support structures (in chronic stress)  Anti-inflammatory effects  Suppresses immune system  In general, its actions oppose those of insulin (somewhat like glucagon); designated F actio
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