Endocrine Exam 3

• Pituitary gland anatomy


  • Epithelial component (Adenohypophysis) - 5 cell types that secrete 6 different hormones
  • Neural component (Neurohypophysis) - Secrete multiple neurohormones

  
• Adenohypophysis


  Composed of pars tuberalis, pars intermedia, pars distalis (nearly all of the adenohypophysis)
• Neurohypophysis


  Composed of median eminence, infundibulum intermedia, pars nervosa
• Pars distalis


  Also known as the anterior pituitary
• Pars nervosa


  Also known as the posterior pituitary
• Antidiuretic hormone (ADH, aka vasopressin)


  One of the two major hormones secreted by the posterior pituitary
• Oxytocin


  One of the two major hormones secreted by the posterior pituitary
• Magnocellular neurons


  • Originating in the PVN and SON
  • Vasopressinergic neurons
  • Oxytotic neurons

  
• Processing of ADH and oxytocin

  1. Signal peptidase

  2. Prohormone convertase 1/3

  3. Prohormone convertase 5

  4. Carboxypeptidase E

  
• ADH and oxytocin are small nonapeptides and only differ by 2 amino acids
• ADH and oxytocin have very different effects
• Secretion of ADH and oxytocin

  1. Stimuli detected at cell bodies in PVN and SON

  2. Depolarization à action potential down axon

  3. Action potential triggers voltage gated Ca2+ channels, resulting in influx of Ca2+

  4. Exocytosis

  
• Osmoreceptive neurons


  Innervate the vasopressinergic magnocellular neurons in the PVN and SON that make ADH

  
• Increased ECF osmolality


  Osmoreceptive neurons shrink à stimulate vassopressinergic magnocellular neurons à action potential down the hypothalamohypophyseal tract à increased intracellular Ca2+ at the axon termini in the posterior pituitary à ADH secretion

  
• Drop in blood volume


  Stimulates ADH secretion
• Cardiovascular baroreceptors


  Located in several parts of the body can influence ADH secretion
• ADH secretion is not very sensitive to changes in blood volume when changes in blood volume are small
• When blood volume drops drastically (>8-10%) ADH secretion becomes quite sensitive to volume changes
• Drops in blood volume makes vasopressinergic neurons more sensitive to changes in osmolality
• A rise in blood volume decreases the sensitivity to changes in osmolality
• Drugs that increase ADH secretion

  • Barbituarates
  • Nicotine
  • Opiates
• Vasopressin-2 (V2) receptors


  Major site of action for ADH is distal convoluted tubule and collecting ducts of nephrons
• What ADH does


  1. Binds to V2 receptors in DCT and collecting ducts

  2. Activates Gs-cAMP-PKA pathway

  3. Increases water reabsorption, decreases urine volume
• At very high concentrations, ADH can bind to V1 receptors on vascular smooth muscle
• During vasodilatory shock, severe blood volume depletion


  ADH levels can increase more than 100-fold, binding to V1 receptors to induce vascular smooth muscle contraction
• Drugs that decrease ADH secretion

  • Alcohol
  • Caffeine
  • Cortisol
• ADH can be degraded by proteolysis in the kidney and liver
• Circulating half-life of ADH is ~15-20 minutes
• Oxytocin receptors


  • GPCR - IP3-Ca2+-DAG pathway
  • Found on uterine smooth muscle, myoepithelial cells in mammary glands, various regions in the brain

  
• Stretching of the vagina and cervix during childbirth

  Stimulates oxytocin secretion
• Suckling, intercourse


  Stimulate a neuroendocrine reflex that triggers oxytocin secretion
• Oxytocin levels rise only after the start of childbirth, may not be the factor that initiates childbirth
• Oxytocin receptors rise nearly 100-fold on uterine smooth muscle during pregnancy
• Labor is likely initiated when oxytocin receptors reach a certain threshold and the uterus becomes very sensitive to oxytocin
• What oxytocin does


  • Stimulates contraction of uterine smooth muscle to help expel baby
  • Causes milk letdown in mammary gland
  • Promotes maternal behavior and bonding in the brain
• Oxytocin has a short half life: 3-5 mins
• Oxytocin is degraded primarily in the kidney, liver, mammary gland and uterus
• Metformin


  Decreases hepatic glucose production in the liver (Biguanides)
• Metformin


  • Side effects: lactic acidosis, increases anaerobic metabolism by blocking pyruvate carboxylase
• Metformin dose


  1500 mg/day every 8-12 hrs within meal, 2550 mg/day