12+11

• Adrenal endocrine organs


  The medulla and the cortex (one surrounding the other)

  
• Adrenal medulla

  • Mainly secretes catecholamines epinephrine, norepinephrine, and dopamine

  
• Adrenal cortex

  • Mainly secretes steroid hormones

  
• Steroid hormones secreted by adrenal cortex


  • Glucocorticoids
  • Mineralocorticoids
  • Androgens

  
• Glucocorticoids


  Widespread effects on the metabolism of carbohydrate and protein
• Mineralocorticoids


  Essential to the maintenance of Na+ balance and extracellular fluid (ECF) volume
• Androgens


  Sex hormones such as testosterone, which can exert effects on reproductive function
• Mineralocorticoids and the glucocorticoids are necessary for survival
• Adrenal medulla


  • Norepinephrine secreting cells (90%)
  • Non-epinephrine secreting cells (10%)

  
• Adrenal cortex


  • Zona glomerulosa (secrete aldosterone and little cortisol and androgens)
  • Zona fasciculata (secrete cortisol and little androgens)
  • Zona reticularis (secrete androgens and little cortisol)

  
• All the 3 zones of the adrenal cortex secrete corticosterone BUT only the glomerulosa contain enzymatic mechanism for aldosterone biosynthesis

  
• Catecholamine synthesis


  1. Tyrosine hydroxylation and decarboxylation give norepinephrine

  2. Norepinephrine methylation give epinephrine

  
• Metabolism of catecholamines


  • By sulfate conjugation in liver (inactive)
  • Dopamine 95% conjugated
  • Norepinephrine & epinephrine 70% are conjugated
  • All have a half-life in circulation ~ 2min

  
• Metabolic effects of epinephrine & norepinephrine

  • Glycogenolysis in liver and skeletal muscle
  • Mobilization of free fatty acids (FFA)
  • Increased plasma lactate
  • Stimulation of the metabolic rate

  
• Via β-adrenergic stimulation


  Increase insulin and glucagon secretion
• Via α-adrenergic stimulation


  Inhibit insulin and glucagon secretion
• Via β1-receptor activation


  Increase the force and rate of contraction of the isolated heart
• Norepinephrine


  Produces vasoconstriction in most if not all organs via α1-receptors

  
• Epinephrine


  Dilates the blood vessels in skeletal muscle and the liver via β2-receptors

  
• Via dopaminergic receptors


  Produce renal vasodilation
• Via releasing norepinephrine


  Produce vasoconstriction on other blood vessels
• Via β1- adrenergic receptors

  Produce positive inotropic effect on the heart
• Local release of dopamine by renal cortex

  Causes natriuresis and may exert this effect by inhibiting renal Na, K, ATPase

  
• Certain drugs act directly on adrenal medulla to change catecholamine secretion

  
• Physiologic stimuli affect adrenal medulla indirectly by stimulation of nervous system (sympathetic autonomic division)

  
• During basal states, the adrenal medulla secretion is low

  
• During sleep, the adrenal medulla secretion is reduced to lesser extent

  
• Emergency situations (Emergency function of sympathoadrenal system) provoke sympathetic discharge to prepare an individual for Fight or Flight in part by increase adrenal medullary secretion

  
• Adrenal cortex hormones


  • Derivatives of cholesterol (27 C)
  • Contain Cyclopenanoperhydrophenanthrene nucleus (17 C)

  
• Significantly secreted steroids of adrenal cortex


  • Aldosterone (mineralocorticoid)
  • Cortisol and corticosterone (glucocorticoids)
  • DHEA and androstenedione (androgens)
  • Deoxycorticosterone (mineralocorticoid)

  
• Deoxycorticosterone


  Has only 3% of aldosterone activity (BUT with the same secretion amount)

  
• Adrenal steroid hormone synthesis

  1. LDL is taken up by adrenal cells

  2. The esterified LDL-cholesterol is freeing by cholesterol ester hydrolase

  3. Free cholesterol is transported by a carrier protein into the mitochondria

  4. Cholesterol is converted to pregnenolone

  5. Some of pregnenolone is converted into progesterone

  
• ACTH receptors


  Membrane bound stimulatory GPCR linked to cAMP system

  
• cAMP

  Enhance cholesterol ester hydrolysis in lipid droplets and thus increase pregnenolone formation

  
• Long period of ACTH stimulation

  Increases P450 synthesis involved in glucocorticoid synthesis

  
• Corticosteroid-binding globulin (CGB)

  • Synthesized by liver
  • Level increase during pregnancy (by estrogen)
  • Level decreased by liver cirrhosis, nephrosis and multiple myeloma (B lymphocyte tumor)

  
• When CBG level increase


  More cortisol is bound, then initial fall in free cortisol, then stimulate ACTH secretion, then more cortisol is secreted

  
• When CBG level decrease

  The opposite direction occurs
• A minor degree of binding to albumin also takes place
• The half-life of cortisol in the circulation is therefore longer (about 60–90 min)