G

• Adrenal Medulla


  Inner part of the adrenal gland that secretes catecholamines: epinephrine, norepinephrine, and dopamine
• Adrenal Cortex


  Outer part of the adrenal gland that secretes steroid hormones: glucocorticoids, mineralocorticoids, and androgens
• The adrenal medulla constitutes 28% of the mass of the adrenal gland
• Cell types in the adrenal medulla


  • Epinephrine-secreting type
  • Norepinephrine-secreting type
• In humans, 90% of the adrenal medulla cells are the epinephrine-secreting type and 10% are the norepinephrine-secreting type

  
• Zones of the adrenal cortex


  • Zona glomerulosa
  • Zona fasciculate
  • Zona reticularis
• Catecholamines


  Norepinephrine, epinephrine, and small amounts of dopamine synthesized by the adrenal medulla
• Catecholamine synthesis


  1. Norepinephrine formed by hydroxylation and decarboxylation of tyrosine

  2. Epinephrine formed by methylation of norepinephrine
• In plasma, about 95% of the dopamine and 70% of the norepinephrine and epinephrine are conjugated to sulfate
• The catecholamines have a half-life of about 2 minutes in the circulation
• Metabolic effects of norepinephrine and epinephrine


  • Glycogenolysis in liver and skeletal muscle
  • Mobilization of free fatty acids
  • Increased plasma lactate
  • Stimulation of metabolic rate
• α- and β-adrenergic receptors


  Receptors that mediate the effects of norepinephrine and epinephrine
• Norepinephrine and epinephrine increase the secretion of insulin and glucagon via β-adrenergic mechanisms and inhibit their secretion via α-adrenergic mechanisms
• Norepinephrine and epinephrine increase the force and rate of contraction of the isolated heart, mediated by β1-receptors
• Norepinephrine produces vasoconstriction in most organs via α1-receptors, but epinephrine dilates blood vessels in skeletal muscle and liver via β2-receptors
• Dopamine


  Physiologic function in the circulation is unknown, but it produces renal vasodilation, mesenteric vasodilation, and positive inotropic effects on the heart
• Dopamine causes natriuresis and may exert this effect by inhibiting renal Na, K, ATPase
• Catecholamine secretion is low in basal states, but is reduced even further during sleep
• Adrenal cortex hormones


  Mineralocorticoids (aldosterone), glucocorticoids (cortisol, corticosterone), and androgens (DHEA, androstenedione)
• Deoxycorticosterone is a mineralocorticoid normally secreted in about the same amount as aldosterone but has only 3% of its mineralocorticoid activity
• Steroid biosynthesis


  1. Cholesterol is the precursor

  2. Cholesterol ester hydrolase catalyzes formation of free cholesterol

  3. Cholesterol transported to mitochondria and converted to pregnenolone

  4. Pregnenolone converted to progesterone in smooth ER

  5. ACTH activates steroid synthesis via cAMP pathway
• Corticosteroid-binding globulin (CBG)


  Binds cortisol in the circulation, keeping a supply of free cortisol available to tissues
• Bound steroids are physiologically inactive, and relatively little free cortisol and corticosterone are found in the urine due to protein binding
• Glucocorticoid metabolism and excretion


  1. Cortisol metabolized in liver to dihydrocortisol and tetrahydrocortisol, which are conjugated to glucuronic acid

  2. Cortisone converted to cortisol in peripheral tissues
• Aldosterone


  Bound to protein to only a slight extent, with a short half-life of about 20 minutes
• 17-ketosteroids


  Adrenal androgens including dehydroepiandrosterone and androstenedione
• In normal adult males, about two-thirds of urinary 17-ketosteroids are of adrenal or hepatic origin, and one-third are of testicular origin
• Adrenal androgens


  Promote protein anabolism and growth, but have less than 20% of the masculinizing activity of testosterone
• Adrenal estrogens


  Androstenedione is converted to estrogens in peripheral tissues, an important source in men and postmenopausal women
• Glucocorticoid mechanism of action


  Bind to glucocorticoid receptors, forming complexes that act as transcription factors to promote transcription of certain DNA segments
• Glucocorticoid effects on intermediary metabolism


  • Increased protein catabolism
  • Increased hepatic glycogenesis and gluconeogenesis
  • Increased glucose-6-phosphatase activity, raising plasma glucose
  • Anti-insulin action in peripheral tissues, worsening diabetes
  • Increased plasma lipid levels and ketone body formation in diabetics
• Testosterone and estrogens


  Converted from in fat and other peripheral tissues
• This is an important source of estrogens in men and postmenopausal women
• Mechanism of action of glucocorticoids


  Binding to glucocorticoid receptors, and the steroid–receptor complexes act as transcription factors that promote the transcription of certain segments of DNA
• Effects of glucocorticoids on intermediary metabolism


  1. Increased protein catabolism

  2. Increased hepatic glycogenesis and gluconeogenesis

  3. Increased glucose-6-phosphatase activity

  4. Plasma glucose level rises

  5. Anti-insulin action in peripheral tissues

  6. Increased plasma lipid levels and ketone body formation in diabetics
• The brain and the heart are spared, so the increase in plasma glucose provides extra glucose to these vital organs
• Effects of glucocorticoids on ACTH secretion


  Inhibit ACTH secretion, which represents a negative feedback response on the pituitary
• Effects of glucocorticoids on the nervous system


  1. Appearance of electroencephalographic waves slower than the normal β rhythm

  2. Personality changes including irritability, apprehension, and inability to concentrate
• Effects of glucocorticoids on water metabolism


  1. Inability to excrete a water load, causing the possibility of water intoxication

  2. Glucose infusion may cause high fever ("glucose fever") followed by collapse and death in patients with adrenal insufficiency who have not received glucocorticoids
• Effects of glucocorticoids on the blood cells & lymphatic organs


  1. Decrease the number of circulating eosinophils

  2. Lower the number of basophils in the circulation

  3. Increase the number of neutrophils, platelets, and red blood cells